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1.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 655-659, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-38955694

ABSTRACT

The 5th edition of the WHO Endocrine and Neuroendocrine Oncology Blue Book, released in 2022, contained some changes in the classification of neuroendocrine tumors. A brief summary of the main changes has been provided in this section. Mainly summarized as changes in naming, differentiation and classification of neuroendocrine tumors, and tumor grading systems related to anatomical locations, morphological characteristics of neuroendocrine tumors in different locations, auxiliary diagnostic and prognostic/therapeutic markers, differential diagnosis and diagnostic difficulties of neuroendocrine tumors.


Subject(s)
Neuroendocrine Tumors , World Health Organization , Humans , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/classification , Diagnosis, Differential , Neoplasm Grading , Biomarkers, Tumor/metabolism , Prognosis
2.
Front Immunol ; 15: 1394497, 2024.
Article in English | MEDLINE | ID: mdl-38947323

ABSTRACT

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.


Subject(s)
Cystadenocarcinoma, Serous , Cytokines , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/immunology , Ovarian Neoplasms/therapy , Ovarian Neoplasms/mortality , Cystadenocarcinoma, Serous/immunology , Cystadenocarcinoma, Serous/therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/blood , Cystadenocarcinoma, Serous/diagnosis , Cytokines/blood , Middle Aged , Aged , Neoadjuvant Therapy , Phenotype , Cytoreduction Surgical Procedures , Biomarkers, Tumor/blood , Neoplasm Grading , Prognosis , Treatment Outcome , Adult
3.
Cancer Imaging ; 24(1): 81, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38956721

ABSTRACT

BACKGROUND: Numerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy (TRUS-Bx). The optimal number of biopsy cores to be obtained per lesion identified on multiparametric MRI (mpMRI) images, however, remains a matter of debate. The aim of this study was to evaluate the incremental value of additional biopsy cores in an MRI-targeted "in-bore"-biopsy (MRI-Bx) setting. PATIENTS AND METHODS: Two hundred and forty-five patients, who underwent MRI-Bx between June 2014 and September 2021, were included in this retrospective single-center analysis. All lesions were biopsied with at least five biopsy cores and cumulative detection rates for any cancer (PCa) as well as detection rates of clinically significant cancers (csPCa) were calculated for each sequentially labeled biopsy core. The cumulative per-core detection rates are presented as whole numbers and as proportion of the maximum detection rate reached, when all biopsy cores were considered. CsPCa was defined as Gleason Score (GS) ≥ 7 (3 + 4). RESULTS: One hundred and thirty-two of 245 Patients (53.9%) were diagnosed with prostate cancer and csPCa was found in 64 (26.1%) patients. The first biopsy core revealed csPCa/ PCa in 76.6% (49/64)/ 81.8% (108/132) of cases. The second, third and fourth core found csPCa/ PCa not detected by previous cores in 10.9% (7/64)/ 8.3% (11/132), 7.8% (5/64)/ 5.3% (7/132) and 3.1% (2/64)/ 3% (4/132) of cases, respectively. Obtaining one or more cores beyond the fourth biopsy core resulted in an increase in detection rate of 1.6% (1/64)/ 1.5% (2/132). CONCLUSION: We found that obtaining five cores per lesion maximized detection rates. If, however, future research should establish a clear link between the incidence of serious complications and the number of biopsy cores obtained, a three-core biopsy might suffice as our results suggest that about 95% of all csPCa are detected by the first three cores.


Subject(s)
Image-Guided Biopsy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Retrospective Studies , Aged , Image-Guided Biopsy/methods , Middle Aged , Prostate/pathology , Prostate/diagnostic imaging , Magnetic Resonance Imaging/methods , Biopsy, Large-Core Needle/methods , Neoplasm Grading , Magnetic Resonance Imaging, Interventional/methods , Multiparametric Magnetic Resonance Imaging/methods
4.
PLoS One ; 19(7): e0304847, 2024.
Article in English | MEDLINE | ID: mdl-38968206

ABSTRACT

This paper presents a novel approach to enhance the accuracy of patch-level Gleason grading in prostate histopathology images, a critical task in the diagnosis and prognosis of prostate cancer. This study shows that the Gleason grading accuracy can be improved by addressing the prevalent issue of label inconsistencies in the SICAPv2 prostate dataset, which employs a majority voting scheme for patch-level labels. We propose a multi-label ensemble deep-learning classifier that effectively mitigates these inconsistencies and yields more accurate results than the state-of-the-art works. Specifically, our approach leverages the strengths of three different one-vs-all deep learning models in an ensemble to learn diverse features from the histopathology images to individually indicate the presence of one or more Gleason grades (G3, G4, and G5) in each patch. These deep learning models have been trained using transfer learning to fine-tune a variant of the ResNet18 CNN classifier chosen after an extensive ablation study. Experimental results demonstrate that our multi-label ensemble classifier significantly outperforms traditional single-label classifiers reported in the literature by at least 14% and 4% on accuracy and f1-score metrics respectively. These results underscore the potential of our proposed machine learning approach to improve the accuracy and consistency of prostate cancer grading.


Subject(s)
Deep Learning , Neoplasm Grading , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Neural Networks, Computer , Prostate/pathology , Algorithms
5.
Acta Neurochir (Wien) ; 166(1): 282, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967664

ABSTRACT

PURPOSE: We conducted a National Cancer Database (NCDB) study to investigate the epidemiological characteristics and identify predictors of outcomes associated with geriatric meningiomas. METHODS: The NCDB was queried for adults aged 60-89 years diagnosed between 2010 and 2017 with grade 2 and 3 meningiomas. The patients were classified into three age groups based on their age: 60-69 (hexagenarians), 70-79 (septuagenarians), and 80-89 (octogenarians). The log-rank test was utilized to compare the differences in overall survival (OS). Univariate and multivariate Cox proportional hazards regressions were used to evaluate the mortality risk associated with various patient and disease parameters. RESULTS: A total of 6585 patients were identified. Hexagenerians were the most common age group (49.8%), with the majority of meningiomas being classified as grade 2 (89.5%). The incidence of high-grade meningiomas increased in all age groups during the study period. Advanced age, male sex, black race, lower socioeconomic status, Charlson-Deyo score ≥ 2, and higher tumor grade were independent factors of poor survival. Among the modes of treatment, the extent of surgical resection, adjuvant radiotherapy, and treatment at a noncommunity cancer program were linked with better outcomes. CONCLUSION: In geriatric patients with high-grade meningiomas, the greater extent of surgical resection and radiotherapy are associated with improved survival. However, the management and outcome of geriatric patients with higher-grade meningiomas are also associated with several socioeconomic factors.


Subject(s)
Databases, Factual , Meningeal Neoplasms , Meningioma , Humans , Meningioma/epidemiology , Meningioma/mortality , Meningioma/pathology , Aged , Male , Middle Aged , Female , Aged, 80 and over , Meningeal Neoplasms/epidemiology , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , United States/epidemiology , Age Factors , Neoplasm Grading
6.
Cancer Imaging ; 24(1): 86, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965552

ABSTRACT

PURPOSE: To develop a radiomics-based model using [68Ga]Ga-PSMA PET/CT to predict postoperative adverse pathology (AP) in patients with biopsy Gleason Grade Group (GGG) 1-2 prostate cancer (PCa), assisting in the selection of patients for active surveillance (AS). METHODS: A total of 75 men with biopsy GGG 1-2 PCa who underwent radical prostatectomy (RP) were enrolled. The patients were randomly divided into a training group (70%) and a testing group (30%). Radiomics features of entire prostate were extracted from the [68Ga]Ga-PSMA PET scans and selected using the minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression model. Logistic regression analyses were conducted to construct the prediction models. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were employed to evaluate the diagnostic value, clinical utility, and predictive accuracy of the models, respectively. RESULTS: Among the 75 patients, 30 had AP confirmed by RP. The clinical model showed an area under the curve (AUC) of 0.821 (0.695-0.947) in the training set and 0.795 (0.603-0.987) in the testing set. The radiomics model achieved AUC values of 0.830 (0.720-0.941) in the training set and 0.829 (0.624-1.000) in the testing set. The combined model, which incorporated the Radiomics score (Radscore) and free prostate-specific antigen (FPSA)/total prostate-specific antigen (TPSA), demonstrated higher diagnostic efficacy than both the clinical and radiomics models, with AUC values of 0.875 (0.780-0.970) in the training set and 0.872 (0.678-1.000) in the testing set. DCA showed that the net benefits of the combined model and radiomics model exceeded those of the clinical model. CONCLUSION: The combined model shows potential in stratifying men with biopsy GGG 1-2 PCa based on the presence of AP at final pathology and outperforms models based solely on clinical or radiomics features. It may be expected to aid urologists in better selecting suitable patients for AS.


Subject(s)
Gallium Isotopes , Gallium Radioisotopes , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Middle Aged , Aged , Prostatectomy/methods , Biopsy/methods , Neoplasm Grading , Oligopeptides , Radiopharmaceuticals , Watchful Waiting/methods , Edetic Acid/analogs & derivatives , Retrospective Studies , Radiomics
7.
Cancer Cell ; 42(7): 1217-1238.e19, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981438

ABSTRACT

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.


Subject(s)
Brain Neoplasms , Glioma , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Signal Transduction , Humans , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Mutation , Proteomics/methods , Protein Processing, Post-Translational , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/metabolism , Phosphorylation , Neoplasm Grading , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism
8.
Front Immunol ; 15: 1427200, 2024.
Article in English | MEDLINE | ID: mdl-38989284

ABSTRACT

Introduction: Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive. Methods: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas. Results: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance. Discussion: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.


Subject(s)
Brain Neoplasms , Gene Expression Profiling , Glioma , Isocitrate Dehydrogenase , Mutation , Single-Cell Analysis , Humans , Isocitrate Dehydrogenase/genetics , Glioma/genetics , Glioma/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Transcriptome , Astrocytes/metabolism , Oncogenes , Down-Regulation , Oligodendrocyte Precursor Cells/metabolism , Neoplasm Grading , Biomarkers, Tumor/genetics
9.
Commun Biol ; 7(1): 824, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971948

ABSTRACT

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.


Subject(s)
Brain Neoplasms , DNA Copy Number Variations , DNA Methylation , Gene Expression Regulation, Neoplastic , Glioma , MicroRNAs , Humans , Glioma/genetics , Glioma/immunology , Glioma/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Epigenomics , Genomics , Gene Regulatory Networks , Cell Line, Tumor , Immune Evasion/genetics , Epigenesis, Genetic , Female , Male , Prognosis , Neoplasm Grading
10.
Front Immunol ; 15: 1420847, 2024.
Article in English | MEDLINE | ID: mdl-38975339

ABSTRACT

High-grade serous ovarian cancer (HGSOC) presents significant challenges due to its heterogeneity and late-stage diagnoses. Using single-cell and spatial transcriptomics to elucidate the complex landscape of HGSOC to understand its underlying mechanism. Our analysis reveals significant inter- and intra-tumoral diversity, manifested through distinct cellular subpopulations and varied microenvironmental niches. Notably, our findings highlight a widespread immunosuppressive environment, marked by complex networks of cell-cell interactions, particularly evident in areas of elevated tumor cell density within metastatic samples. We identify the exclusive presence of COL14A1+ neoplastic cells in metastatic specimens, alongside a strong correlation between CD8A+ NKT cells and poor prognosis, and elevated CHODL expression in HGSOC metastasis tissues. Furthermore, knockdown experiments targeting CHODL demonstrate its role in reducing migration and invasion abilities in HGSOC cells. A pivotal discovery of our study is the delineation of specific cellular signatures correlated with adverse outcomes, notably a subset of CHODL+ neoplastic cells characterized by a distinct metabolic phenotype with a predilection for lipid metabolism. The therapeutic targeting of this metabolic pathway with existing inhibitors appears promising in curbing tumor proliferation. These findings enhance our understanding of HGSOC heterogeneity and reveal potential therapeutic targets, promising more effective management strategies for this aggressive cancer subtype.


Subject(s)
Cystadenocarcinoma, Serous , Ovarian Neoplasms , Single-Cell Analysis , Tumor Microenvironment , Female , Humans , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Tumor Microenvironment/genetics , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Gene Expression Profiling , Transcriptome , Cell Line, Tumor , Neoplasm Grading , Gene Expression Regulation, Neoplastic , Genetic Heterogeneity , Biomarkers, Tumor/genetics , Prognosis
11.
BMC Med Imaging ; 24(1): 171, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992609

ABSTRACT

BACKGROUND: Distinguishing high-grade from low-grade chondrosarcoma is extremely vital not only for guiding the development of personalized surgical treatment but also for predicting the prognosis of patients. We aimed to establish and validate a magnetic resonance imaging (MRI)-based nomogram for predicting preoperative grading in patients with chondrosarcoma. METHODS: Approximately 114 patients (60 and 54 cases with high-grade and low-grade chondrosarcoma, respectively) were recruited for this retrospective study. All patients were treated via surgery and histopathologically proven, and they were randomly divided into training (n = 80) and validation (n = 34) sets at a ratio of 7:3. Next, radiomics features were extracted from two sequences using the least absolute shrinkage and selection operator (LASSO) algorithms. The rad-scores were calculated and then subjected to logistic regression to develop a radiomics model. A nomogram combining independent predictive semantic features with radiomic by using multivariate logistic regression was established. The performance of each model was assessed by the receiver operating characteristic (ROC) curve analysis and the area under the curve, while clinical efficacy was evaluated via decision curve analysis (DCA). RESULTS: Ultimately, six optimal radiomics signatures were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging with fat suppression (T2WI-FS) sequences to develop the radiomics model. Tumour cartilage abundance, which emerged as an independent predictor, was significantly related to chondrosarcoma grading (p < 0.05). The AUC values of the radiomics model were 0.85 (95% CI, 0.76 to 0.95) in the training sets, and the corresponding AUC values in the validation sets were 0.82 (95% CI, 0.65 to 0.98), which were far superior to the clinical model AUC values of 0.68 (95% CI, 0.58 to 0.79) in the training sets and 0.72 (95% CI, 0.57 to 0.87) in the validation sets. The nomogram demonstrated good performance in the preoperative distinction of chondrosarcoma. The DCA analysis revealed that the nomogram model had a markedly higher clinical usefulness in predicting chondrosarcoma grading preoperatively than either the rad-score or clinical model alone. CONCLUSION: The nomogram based on MRI radiomics combined with optimal independent factors had better performance for the preoperative differentiation between low-grade and high-grade chondrosarcoma and has potential as a noninvasive preoperative tool for personalizing clinical plans.


Subject(s)
Bone Neoplasms , Chondrosarcoma , Magnetic Resonance Imaging , Neoplasm Grading , Nomograms , Humans , Chondrosarcoma/diagnostic imaging , Chondrosarcoma/pathology , Chondrosarcoma/surgery , Magnetic Resonance Imaging/methods , Female , Male , Retrospective Studies , Middle Aged , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Bone Neoplasms/pathology , Adult , Aged , ROC Curve , Young Adult , Radiomics
12.
Cells ; 13(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38994952

ABSTRACT

Endometrial cancer (EC) is a significant cause of cancer-related deaths in women. MicroRNAs (miRs) play a role in cancer development, acting as oncogenes or tumor suppressors. This study evaluated the diagnostic potential of hsa-miR-185-5p and hsa-miR-191-5p in EC and their correlation with clinical and histopathological features. A cross-sectional study analyzed formalin-fixed, paraffin-embedded tissue samples from 59 patients: 18 with EC, 21 with endometrial hyperplasia (EH), 17 with normal endometrium (NE), and 3 with endometrial polyps (EPs). Quantitative reverse transcription-polymerase chain reaction and TaqMan probes were used for miR expression analysis. The Shapiro-Wilk test was used to analyze the normal distribution of the data. Subsequently, parametric or non-parametric tests were used to evaluate the associations between the expression levels of each miR and clinical parameters. Both miRs were underexpressed in some precursor and malignant lesions compared to certain NE subtypes and benign lesions. Specifically, hsa-miR-185-5p showed underexpression in grade 3 EC compared to some NE and EH subtypes (FC: -57.9 to -8.5, p < 0.05), and hsa-miR-191-5p was underexpressed in EH and EC compared to secretory endometrium and EPs (FC: -4.2 to -32.8, p < 0.05). SETD1B, TJP1, and MSI1 were common predicted target genes. In conclusion, hsa-miR-185-5p and hsa-miR-191-5p are underexpressed in EC tissues, correlating with histopathological grades, highlighting their potential as diagnostic biomarkers and their role as tumor suppressors in EC.


Subject(s)
Endometrial Neoplasms , Endometrium , Gene Expression Regulation, Neoplastic , MicroRNAs , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Endometrium/metabolism , Endometrium/pathology , Middle Aged , Cross-Sectional Studies , Neoplasm Grading , Adult , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism
13.
PLoS One ; 19(7): e0301653, 2024.
Article in English | MEDLINE | ID: mdl-38990870

ABSTRACT

BACKGROUND: To systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity. RESULTS: Thirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses. CONCLUSIONS: PGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.


Subject(s)
Margins of Excision , Neoplasm Recurrence, Local , Prostatectomy , Prostatic Neoplasms , Humans , Prostatectomy/methods , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Male , Neoplasm Recurrence, Local/pathology , Neoplasm Grading , Neoplasm Staging , Prostate-Specific Antigen/blood , Prostate-Specific Antigen/metabolism
14.
Nat Commun ; 15(1): 5932, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013886

ABSTRACT

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8+PD-1+ T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome immune resistance of ovarian cancers.


Subject(s)
Antibodies, Monoclonal, Humanized , Neoadjuvant Therapy , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/immunology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Neoadjuvant Therapy/methods , Antibodies, Monoclonal, Humanized/therapeutic use , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Tumor Microenvironment/immunology , Tumor Microenvironment/drug effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Neoplasm Grading , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/antagonists & inhibitors , Immunotherapy/methods
15.
J Ovarian Res ; 17(1): 149, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020428

ABSTRACT

BACKGROUND: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery. RESULTS: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC. CONCLUSIONS: This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.


Subject(s)
Biomarkers, Tumor , Early Detection of Cancer , Extracellular Vesicles , Mucin-1 , Ovarian Neoplasms , Proteomics , Humans , Female , Extracellular Vesicles/metabolism , Proteomics/methods , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Biomarkers, Tumor/blood , Early Detection of Cancer/methods , Middle Aged , Mucin-1/blood , Cystadenocarcinoma, Serous/blood , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/pathology , Aged , Neoplasm Grading , Adult
16.
Technol Cancer Res Treat ; 23: 15330338241262483, 2024.
Article in English | MEDLINE | ID: mdl-39043042

ABSTRACT

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.


Subject(s)
Astrocytoma , Spinal Cord Neoplasms , Humans , Astrocytoma/genetics , Astrocytoma/therapy , Astrocytoma/diagnosis , Astrocytoma/pathology , Spinal Cord Neoplasms/therapy , Spinal Cord Neoplasms/genetics , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology , Biomarkers, Tumor/genetics , Pathology, Molecular , DNA Methylation , Disease Management , Prognosis , Neoplasm Grading
17.
BMC Med Imaging ; 24(1): 177, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030508

ABSTRACT

BACKGROUND: Cancer pathology shows disease development and associated molecular features. It provides extensive phenotypic information that is cancer-predictive and has potential implications for planning treatment. Based on the exceptional performance of computational approaches in the field of digital pathogenic, the use of rich phenotypic information in digital pathology images has enabled us to identify low-level gliomas (LGG) from high-grade gliomas (HGG). Because the differences between the textures are so slight, utilizing just one feature or a small number of features produces poor categorization results. METHODS: In this work, multiple feature extraction methods that can extract distinct features from the texture of histopathology image data are used to compare the classification outcomes. The successful feature extraction algorithms GLCM, LBP, multi-LBGLCM, GLRLM, color moment features, and RSHD have been chosen in this paper. LBP and GLCM algorithms are combined to create LBGLCM. The LBGLCM feature extraction approach is extended in this study to multiple scales using an image pyramid, which is defined by sampling the image both in space and scale. The preprocessing stage is first used to enhance the contrast of the images and remove noise and illumination effects. The feature extraction stage is then carried out to extract several important features (texture and color) from histopathology images. Third, the feature fusion and reduction step is put into practice to decrease the number of features that are processed, reducing the computation time of the suggested system. The classification stage is created at the end to categorize various brain cancer grades. We performed our analysis on the 821 whole-slide pathology images from glioma patients in the Cancer Genome Atlas (TCGA) dataset. Two types of brain cancer are included in the dataset: GBM and LGG (grades II and III). 506 GBM images and 315 LGG images are included in our analysis, guaranteeing representation of various tumor grades and histopathological features. RESULTS: The fusion of textural and color characteristics was validated in the glioma patients using the 10-fold cross-validation technique with an accuracy equals to 95.8%, sensitivity equals to 96.4%, DSC equals to 96.7%, and specificity equals to 97.1%. The combination of the color and texture characteristics produced significantly better accuracy, which supported their synergistic significance in the predictive model. The result indicates that the textural characteristics can be an objective, accurate, and comprehensive glioma prediction when paired with conventional imagery. CONCLUSION: The results outperform current approaches for identifying LGG from HGG and provide competitive performance in classifying four categories of glioma in the literature. The proposed model can help stratify patients in clinical studies, choose patients for targeted therapy, and customize specific treatment schedules.


Subject(s)
Algorithms , Brain Neoplasms , Color , Glioma , Neoplasm Grading , Humans , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/classification , Glioma/diagnostic imaging , Glioma/pathology , Glioma/classification , Diagnosis, Computer-Assisted/methods , Image Interpretation, Computer-Assisted/methods
18.
Eur J Med Res ; 29(1): 377, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030639

ABSTRACT

OBJECTIVES: To explore the value of preoperative magnetic resonance imaging (MRI) characterization of intracranial solitary fibrous tumors (ISFT) and to evaluate the effectiveness of preoperative MRI features in predicting pathological grading. MATERIALS AND METHODS: This retrospective analysis comprised the clinical and preoperative MRI characterization of 55 patients with ISFT in our hospital, including 27 grade II cases and 28 grade III cases confirmed by postoperative pathology. Variables included age, sex, tumor location, cross-midline status, signal characteristics of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), T2-fluid-attenuated inversion recovery (T2-FLAIR), and diffusion­weighted imaging (DWI), peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel, maximum tumor diameter, maximum, minimum, and average values of apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumors enhancement mode, meningeal tail sign, skull invasion, cerebral parenchymal invasion, and venous sinus involvement. The independent samples t test or Mann-Whitney U test was performed to compare continuous data between the two groups, and the Pearson chi-squared test or Fisher's exact test was used to compare categorical data. In addition, bivariate logistic regression was performed to construct a comprehensive model, and receiver operating characteristic (ROC) curves were generated to calculate the areas under the curve (AUCs), thereby determining the value of each parameter in the differential diagnosis of grades II and III ISFT. RESULTS: The mean age at onset was similar between patients with grades II and III ISFT (46.77 ± 14.66 years and 45.82 ± 12.07 years, respectively). The proportions of men among patients with grades II and III ISFT were slightly higher than those of female patients (male/female: 1.25 [15/12] and 1.33 [16/12], respectively). There were significant differences between grades II and III ISFT in the T2-FLAIR and DWI signal characteristics, maximum, minimum, and average values of the apparent diffusion coefficient (ADCmax, ADCmin, and ADCmean), tumor location, and skull invasion (P = 0.001, P = 0.018, P = 0.000, P = 0.000, P = 0.000, P = 0.010, and P = 0.032, respectively). However, no significant differences were noted between grades II and III ISFT in age, sex, cross-midline status, T1WI and T2WI signal characteristics, peritumoral edema, intralesional hemorrhage, focal necrosis/cystic degeneration, tumor empty vessel shadow, enhancement mode, meningeal tail sign, maximum tumor diameter, brain parenchyma invasion, or venous sinus involvement (all P > 0.05). Moreover, binary logistic regression analysis showed that the model accuracy was 89.1% when ADCmin was included in the regression equation. Moreover, ROC curve analysis showed that the AUC of ADCmin was 0.805 (0.688, 0.922), sensitivity was 74.1%, specificity was 75.0%, and the cutoff value was 672 mm2/s. CONCLUSIONS: Grade III ISFT patients displayed more mixed T2-FLAIR signal characteristics and DWI signal characteristics than grade II patients, as shown by higher skull invasion and tumor mass collapse midline distribution and lower ADCmax, ADCmean, and ADCmin values. The ADCmin value was significant in the preoperative assignment of grades II and III ISFT, thereby contributing to enhanced accuracy in the imaging grading diagnosis of the disease.


Subject(s)
Brain Neoplasms , Magnetic Resonance Imaging , Humans , Female , Male , Middle Aged , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Magnetic Resonance Imaging/methods , Retrospective Studies , Neoplasm Grading/methods , Aged , Young Adult , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/pathology , Adolescent , Diffusion Magnetic Resonance Imaging/methods , Preoperative Period , Preoperative Care/methods
19.
J Ovarian Res ; 17(1): 145, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997720

ABSTRACT

OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.


Subject(s)
Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms , Paclitaxel , Humans , Female , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Hyperthermic Intraperitoneal Chemotherapy/methods , Middle Aged , Ovarian Neoplasms/therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Adult , Aged , Treatment Outcome , Neoadjuvant Therapy/methods , Neoplasm Staging , Neoplasm Grading , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cystadenocarcinoma, Serous/therapy , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Combined Modality Therapy
20.
Breast Cancer Res ; 26(1): 115, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978071

ABSTRACT

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77-0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed.


Subject(s)
Breast Neoplasms , Lymphocytes , Stromal Cells , Tumor Microenvironment , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Tumor Microenvironment/immunology , Middle Aged , Aged , Lymphocytes/immunology , Lymphocytes/pathology , Stromal Cells/pathology , Adult , Neoplasm Grading , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/immunology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/immunology , Biomarkers, Tumor
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