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1.
Int J Mol Sci ; 23(6)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760653

ABSTRACT

Lung cancer (LC) is the leading cause of cancer-related death worldwide. Although the diagnosis and treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 80% of LC cases, have greatly improved in the past decade, there is still an urgent need to find more sensitive and specific screening methods. Recently, new molecular biomarkers are emerging as potential non-invasive diagnostic agents to screen NSCLC, including multiple microRNAs (miRNAs) that show an unusual expression profile. Moreover, peripheral blood mononuclear cells' (PBMCs) miRNA profile could be linked with NSCLC and used for diagnosis. We developed a molecular beacon (MB)-based miRNA detection strategy for NSCLC. Following PBMCs isolation and screening of the expression profile of a panel of miRNA by RT-qPCR, we designed a MB targeting of up-regulated miR-21-5p. This MB 21-5p was characterized by FRET-melting, CD, NMR and native PAGE, allowing the optimization of an in-situ approach involving miR-21-5p detection in PBMCs via MB. Data show the developed MB approach potential for miR-21-5p detection in PBMCs from clinical samples towards NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic , Humans , Leukocytes, Mononuclear/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , MicroRNAs/metabolism
2.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1662689

ABSTRACT

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.


Subject(s)
Breast Neoplasms/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Case-Control Studies , Cohort Studies , Disease Progression , Female , Humans , Immunohistochemistry/methods , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/metabolism , Metalloproteases/genetics , Metalloproteases/metabolism , Middle Aged , Retrospective Studies , Spain , Tissue Inhibitor of Metalloproteinases/metabolism
3.
J Nanobiotechnology ; 19(1): 287, 2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1662419

ABSTRACT

Pancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs' GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).


Subject(s)
Early Detection of Cancer/methods , Pancreatic Neoplasms/diagnosis , RNA, Messenger/isolation & purification , Biomarkers, Tumor/genetics , COVID-19 , Extracellular Vesicles , Glypicans/genetics , Gold , Humans , Metal Nanoparticles , Pancreatic Neoplasms/genetics
4.
Gastroenterology ; 161(3): 785-791, 2021 09.
Article in English | MEDLINE | ID: covidwho-1626143

ABSTRACT

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.


Subject(s)
Biomedical Research/trends , Pancreatic Neoplasms , Animals , Biomarkers, Tumor/genetics , COVID-19 , Cell Lineage , Diffusion of Innovation , Genetic Predisposition to Disease , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Tumor Microenvironment , Videoconferencing
5.
J Surg Oncol ; 125(4): 596-602, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1592572

ABSTRACT

BACKGROUND AND OBJECTIVES: With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. METHODS: Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. RESULTS: We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CONCLUSIONS: CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Clinical Decision Rules , Genomics , Adult , Aged , Aged, 80 and over , Biopsy, Large-Core Needle , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Reproducibility of Results , Risk Assessment
6.
Sci Immunol ; 5(44)2020 02 21.
Article in English | MEDLINE | ID: covidwho-1575907

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.


Subject(s)
Breast Neoplasms/pathology , Myeloid-Derived Suppressor Cells/pathology , Single-Cell Analysis , Transcriptome , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Breast Neoplasms/immunology , Cell Differentiation/genetics , Female , Humans , Mice , Mice, Inbred Strains , Mice, Transgenic , Myeloid-Derived Suppressor Cells/immunology , RNA, Neoplasm/genetics , RNA, Neoplasm/immunology , Signaling Lymphocytic Activation Molecule Family/genetics , Signaling Lymphocytic Activation Molecule Family/immunology
7.
Int J Biol Sci ; 17(12): 3224-3238, 2021.
Article in English | MEDLINE | ID: covidwho-1524470

ABSTRACT

Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-positive breast cancer. BC-N102 treatment exhibits dose-dependent cytotoxic effects against ER+ breast cancer cell lines. BC-N102 exhibited time course- and dose-dependent cell cycle arrest via downregulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-Akt, CDK2, and CDK4 while increasing p38 mitogen-activated protein kinase (MAPK), and mineralocorticoid receptor (MR) signaling in breast cancer cell line. In addition, we found that BC-N102 suppressed breast cancer tumorigenesis in vivo and prolonged the survival of animals. Our results suggest that the proper application of BC-N102 may be a beneficial chemotherapeutic strategy for ER+ breast cancer patients.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/metabolism , G1 Phase/drug effects , Receptors, Estrogen/metabolism , Resting Phase, Cell Cycle/drug effects , Animals , Biomarkers, Tumor/genetics , Blotting, Western , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Division , Cell Line, Tumor , Cyclin-Dependent Kinase 2/genetics , Cyclin-Dependent Kinase 4/genetics , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic/physiology , Humans , Maximum Tolerated Dose , Mice , Mice, Nude , Xenograft Model Antitumor Assays
8.
Environ Sci Pollut Res Int ; 29(15): 22012-22030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1514070

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here, we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman's correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), and cellular component (CC) as well as to pathways, specific organs, cells, and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene, and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally, methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.


Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology
9.
Int J Mol Sci ; 22(21)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1512375

ABSTRACT

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.


Subject(s)
Rhabdomyosarcoma/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Genomics/methods , Humans , Male , Microsatellite Instability , Mutation/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Up-Regulation
10.
Eur Rev Med Pharmacol Sci ; 25(20): 6411-6424, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1503073

ABSTRACT

OBJECTIVE: The heterogeneity of clinical manifestations and mortality rates in Coronavirus disease 2019 (COVID-19) patients may be related to the existence of molecular subtypes in COVID-19. To improve current management, it is essential to find the hub genes and pathways associated with different COVID-19 subtypes. MATERIALS AND METHODS: The whole-genome sequencing information (GSE156063, GSE163151) of nasopharyngeal swabs from normal subjects and COVID-19 patients were downloaded from the Gene Expression Omnibus (GEO) database. The molecular subtypes of patients with COVID-19 were classified using the "consistent clustering" method, and the specific genes associated with each subtype were found. Differentially expressed genes (DEGs) were screened between normal subjects and COVID-19 patients; the Weighted gene co-expression network analysis (WGCNA) method was used to find the key module genes of COVID-19 patients. Subtype-specific, differentially expressed and module-related genes were collected and intersected. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out and protein-protein interaction (PPI) networks were generated. The pathways enriched in COVID-19 subtypes were analyzed by gene set variation analysis (GSVA). RESULTS: Patients with COVID-19 were divided into three subtypes, and there was no significant difference in gender and age distribution between subtypes. 82 differential gene pathways were screened between Subtypes I and II, 131 differential gene pathways were screened between Subtypes I and III, and 107 differential gene pathways were screened between Subtypes II and III. Finally, 44 differentially expressed key genes were screened, including 11 hub genes (RSAD2, IFIT1, MX1, OAS1, OAS2, BST2, IFI27, IFI35, IFI6, IFITM3, STAT2). CONCLUSIONS: There are significant differences in gene activation and pathway enrichment among different molecular subtypes of COVID-19, which may account for the heterogeneity in clinical presentation and the prognosis of patients.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/genetics , Oligonucleotide Array Sequence Analysis , COVID-19/diagnosis , Genetic Variation/genetics , Humans
11.
Technol Cancer Res Treat ; 20: 15330338211035037, 2021.
Article in English | MEDLINE | ID: covidwho-1484272

ABSTRACT

BACKGROUND: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens. AIM: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations. METHODS: Consecutive ODx results on breast CNBs with invasive carcinoma from 2012-2020 at 3 tertiary care hospitals with dedicated Breast Health Centers were reviewed. Clinical indications to perform ODx on CNB were recorded through a review of patients' electronic medical records. Clinicopathologic features, surgical or oncologic modalities and follow-up data were recorded. RESULTS: Three distinct clinical indications for performing ODx on CNB in 85 ER+ invasive breast carcinomas were identified: 1) Excisions with insufficient tissue to perform ODx, 2) adjudicate neoadjuvant therapy versus primary surgical resection, and 3) select neoadjuvant chemotherapy (NAC) versus neoadjuvant endocrine therapy (NET). Primary surgery was selected in patients with low score RS (<18), and NET was preferred in patients with intermediate or high RS (>18). NET was preferred over NAC in patients with low RS (<18). CONCLUSION: This study shows that CNB ODx RS helps guide treatment decisions in a neoadjuvant setting along with other contributing factors such as the presence of pathogenic mutations, node positivity, patient age, and comorbidities. The use of ODx on CNB is furthermore valuable in the midst of the COVID-19 pandemic for early breast cancer patients to administer effective therapy in a timely manner.


Subject(s)
Breast Neoplasms, Male/diagnosis , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biopsy, Large-Core Needle , Breast Neoplasms/pathology , Breast Neoplasms, Male/pathology , Carcinoma , Carcinoma, Ductal, Breast/pathology , Combined Modality Therapy , Electronic Health Records , Female , Gene Expression Profiling/methods , Genomics , Hormones/therapeutic use , Humans , Male , Medical Oncology , Middle Aged , Neoadjuvant Therapy , Neoplasm Invasiveness , Retrospective Studies , Treatment Outcome
12.
JAMA Netw Open ; 4(9): e2124483, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1396814

ABSTRACT

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.


Subject(s)
Colorectal Neoplasms/pathology , Communicable Disease Control/organization & administration , Patient Acceptance of Health Care , Tumor Burden , Adult , Aged , Biomarkers, Tumor/genetics , COVID-19/epidemiology , Circulating Tumor DNA/blood , Clinical Trials, Phase II as Topic , Cohort Studies , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Controlled Before-After Studies , Female , Humans , Male , Middle Aged , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
13.
Cancer Treat Res Commun ; 27: 100321, 2021.
Article in English | MEDLINE | ID: covidwho-1385378

ABSTRACT

BACKGROUND: ACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression levels of ACE2 among the different subtypes of breast cancer has not been investigated. METHODS: We have examined the differential expression of ACE2 and its correlation with prognosis in breast cancer subtypes using the METABRIC (n = 1898) and TCGA (n = 832) cohorts. Correlations were evaluated by Pearsons's correlation co-efficient and Kaplan-Meier analysis was used to estimate differences in disease-free survival between the ACE2 high and ACE2 low groups. RESULTS: There is minimal expression of ACE2 in the luminal classes, but significantly higher levels in the Basal-like and HER2-enriched subclasses. Metastatic biopsies of these tumor types also show enhanced expression of ACE2. High levels of ACE2 correlated with decreased disease-free survival in the HER2-enriched subtype, and it was positively correlated with EGFR expression. CONCLUSION: These observations suggest ACE2 might function as a context dependent factor driving tumor progression in breast cancer and permit new opportunities for targeted therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Prognosis
14.
Ann Diagn Pathol ; 54: 151800, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1321982

ABSTRACT

BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.


Subject(s)
Biomarkers, Tumor/genetics , Femoral Neoplasms/genetics , Gene Fusion , Head and Neck Neoplasms/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Thoracic Neoplasms/genetics , Adolescent , Adult , Aged , Algorithms , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Extremities/pathology , Female , Femoral Neoplasms/diagnosis , Femoral Neoplasms/drug therapy , Femoral Neoplasms/pathology , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Neoplasm Grading , Phenotype , Prognosis , Sarcoma/diagnosis , Sarcoma/drug therapy , Sarcoma/pathology , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/pathology , Thoracic Neoplasms/diagnosis , Thoracic Neoplasms/drug therapy , Thoracic Neoplasms/pathology , Thoracic Wall/pathology , Young Adult
15.
Int J Mol Sci ; 22(9)2021 Apr 27.
Article in English | MEDLINE | ID: covidwho-1231494

ABSTRACT

Artificial intelligence, or the discipline of developing computational algorithms able to perform tasks that requires human intelligence, offers the opportunity to improve our idea and delivery of precision medicine. Here, we provide an overview of artificial intelligence approaches for the analysis of large-scale RNA-sequencing datasets in cancer. We present the major solutions to disentangle inter- and intra-tumor heterogeneity of transcriptome profiles for an effective improvement of patient management. We outline the contributions of learning algorithms to the needs of cancer genomics, from identifying rare cancer subtypes to personalizing therapeutic treatments.


Subject(s)
Artificial Intelligence , Neoplasms/genetics , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Algorithms , Biomarkers, Tumor/genetics , Humans , Neoplasms/mortality , Neoplasms/pathology , Precision Medicine/methods , Prognosis , Tumor Microenvironment/genetics
16.
Colorectal Dis ; 23(5): 1030-1042, 2021 05.
Article in English | MEDLINE | ID: covidwho-1012951

ABSTRACT

AIM: There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID-19 pandemic, there will be a wait-list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta-analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer. METHODS: The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian-Laird method with random-effects model was utilized for meta-analysis. RESULTS: Forty-six studies totaling 16 149 patients were included in the meta-analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). CONCLUSIONS: Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.


Subject(s)
COVID-19 , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/statistics & numerical data , Feces/chemistry , Genetic Testing/statistics & numerical data , Adult , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , DNA Methylation/genetics , Early Detection of Cancer/methods , False Negative Reactions , False Positive Reactions , Female , Genetic Testing/methods , Humans , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Sensitivity and Specificity
17.
Tumori ; 107(6): NP24-NP27, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-992257

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare tumor, accounting for about 1% of all pancreatic exocrine cancers. Consensus on the management of metastatic PACC remains unclear. CASE PRESENTATION: Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. After progression of disease evaluated based on RECIST 1.1, toripalimab and SOX regimen was administered because of PD-L1-positive expression, high tumor mutation burden (TMB), and somatic FANCA deletion in the tumor. Both the primary and metastatic tumor mass shrank significantly after two courses. The patient exhibited sustained partial response for at least six courses with well-controlled toxic effects. Then the treatment had to be stopped for 2 months because of the coronavirus disease 2019 pandemic. Computed tomography scan in March 2020 showed disease progression. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. CONCLUSIONS: We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/metabolism , Biomarkers, Tumor/genetics , Carcinoma, Acinar Cell/drug therapy , Immunotherapy/methods , Mutation , Pancreatic Neoplasms/drug therapy , Aged , Albumins/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/immunology , Carcinoma, Acinar Cell/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Male , Paclitaxel/administration & dosage , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology
18.
DNA Cell Biol ; 40(2): 359-372, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-963006

ABSTRACT

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs (SPBRs) signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all p < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/complications , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Nomograms , RNA, Messenger/genetics , SARS-CoV-2/isolation & purification , Biomarkers, Tumor/metabolism , COVID-19/transmission , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Cohort Studies , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/virology , Male , Middle Aged , Prognosis , RNA, Messenger/metabolism , Survival Rate
19.
FEBS J ; 287(17): 3677-3680, 2020 09.
Article in English | MEDLINE | ID: covidwho-960856

ABSTRACT

Coronavirus disease 2019 (COVID-19), the highly contagious illness caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the globe, becoming one of the most challenging public health crisis of our times. SARS-CoV-2 can cause severe disease associated with multiple organ damage. Cancer patients have a higher risk of SARS-CoV-2 infection and death. While the virus uses angiotensin-converting enzyme 2 (ACE2) as the primary entry receptor, the recent experimental and clinical findings suggest that some tumor markers, including CD147 (basigin), can provide an additional entry for SARS-CoV-2 infection through binding to the viral spike (S) protein. In the absence of specific viral drugs, blocking of CD147 might be a way to prevent virus invasion. Identifying other target proteins is of high importance as targeting the alternative receptors for SARS-CoV-2 might open up a promising avenue for the treatment of COVID-19 patients, including those who have cancer.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Basigin/antagonists & inhibitors , Biomarkers, Tumor/antagonists & inhibitors , COVID-19/drug therapy , Neoplasms/drug therapy , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Basigin/genetics , Basigin/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/virology , Protein Binding , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
20.
Genomics ; 112(6): 4912-4923, 2020 11.
Article in English | MEDLINE | ID: covidwho-752713

ABSTRACT

COVID-19 is a pandemic that began to spread worldwide caused by SARS-CoV-2. Lung cancer patients are more susceptible to SARS-CoV-2 infection. The SARS-CoV-2 enters into the host by the ACE2 receptor. Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). Therefore, we investigated the prognosis, clinical characteristics, and mutational analysis of lung cancer. We also analyzed the shared proteins between the COVID-19 and lung cancer, protein-protein interactions, gene-miRNAs, gene-transcription factors (TFs), and the signaling pathway. Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. The functional assessment of targeted 12,671, 3107, and 29 positive genes were found in COVID-19 disease, LUAD, and LUSC, respectively. Then, we identified eight common genes that interact with 20 genes, 219 miRNAs, and 16 TFs. The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. This study uncovers the relationship between COVID-19 disease and lung cancer. We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Lung Neoplasms/pathology , Lung Neoplasms/virology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , Adenocarcinoma of Lung/pathology , Adult , Aged , Aged, 80 and over , Biomarkers , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Computational Biology/methods , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , MicroRNAs , Middle Aged , Mutation , Protein Interaction Maps/genetics , Young Adult
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