Perioperative change of circulating tumor cells in cytoreductive radical prostatectomy for oligometastatic hormone-sensitive prostate cancer: the preliminary safety evidence from long-term oncologic outcomes.

Surgical manipulation has a risk of triggering the shedding of circulating tumor cells (CTCs) in patients with malignancies, However, perioperative change of circulating tumor cells in cytoreductive radical prostatectomy (CRP) for patients with oligometastatic hormone-sensitive prostate cancer (omHSPC) has not yet been well documented. This study aimed to assess whether CRP is a safe procedure for patients with omHSPC by monitoring the perioperative change of CTCs and investigating its impact on long-term oncologic outcomes. We have observed a significant decrease between the median CTC counts before and after surgery (6 vs. 4, p = 0.026). Comparing preoperative and postoperative CTC levels, seven patients increased (CTC increase group), one did not change and nineteen decreased (CTC non-increase group). PSA response rates in CTC increase group were lower than those in CTC non-increase group (73.0% vs 99.8%, p = 0.162), and nadir PSA was higher in CTC increase group (0.043 vs 0.003, p = 0.072). The CTC increase was positively correlated with the nadir PSA (r = 0.386, p = 0.047). The median follow-up period was 71.6 months, we found that there was no significant difference in clinical-pathological, operative variables or long-term oncologic outcomes between perioperative CTC increase and non-increase groups. In the entire cohort, the CTC level significantly decreased after surgery. There was no significant differences in long-term oncologic outcomes between the CTC increase and non-increase groups, implying that CRP potentially represents a safe procedure for the treatment of patients with omHSPC. The results need to be confirmed in a prospective large-scale clinical trial.

Urological cancer organoids, patients' avatars for precision medicine: past, present and future.

Urological cancers are common malignant cancers worldwide, with annually increasing morbidity and mortality rates. For decades, two-dimensional cell cultures and animal models have been widely used to study the development and underlying molecular mechanisms of urological cancers. However, they either fail to reflect cancer heterogeneity or are time-consuming and labour-intensive. The recent emergence of a three-dimensional culture model called organoid has the potential to overcome the shortcomings of traditional models. For example, organoids can recapitulate the histopathological and molecular diversity of original cancer and reflect the interaction between cancer and surrounding cells or stroma by simulating tumour microenvironments. Emerging evidence suggests that urine-derived organoids can be generated, which could be a novel non-invasive liquid biopsy method that provides new ideas for clinical precision therapy. However, the current research on organoids has encountered some bottlenecks, such as the lack of a standard culture process, the need to optimize the culture medium and the inability to completely simulate the immune system in vivo. Nonetheless, cell co-culture and organoid-on-a-chip have significant potential to solve these problems. In this review, the latest applications of organoids in drug screening, cancer origin investigation and combined single-cell sequencing are illustrated. Furthermore, the development and application of organoids in urological cancers and their challenges are summarised.

Recent Trends in the Incidence of Clear Cell Adenocarcinoma and Survival Outcomes: A SEER Analysis.

Background: Clear cell adenocarcinoma (CCA) is considered a relatively rare tumor with a glycogen-rich phenotype. The prognosis of CCA patients is unclear. In this study, recent trends in the epidemiological and prognostic factors of CCA were comprehensively investigated. Methods: Patients with CCA from years 2000 to 2016 were identified from the Surveillance, Epidemiological, and End Results (SEER) database. Relevant population data were used to analyze the rates age-adjusted incidence, age-standardized 3-year and 5-year relative survivals, and overall survival (OS). Results: The age-adjusted incidence of CCA increased 2.7-fold from the year 2000 (3.3/100,000) to 2016 (8.8/100,000). This increase occurred across all ages, races, stages, and grades. Of all these subgroups, the increase was largest in the grade IV group. The age-standardized 3-year and 5-year relative survivals increased during this study period, rising by 9.1% and 9.5% from 2000 to 2011, respectively. Among all the stages and grades, the relative survival increase was greatest in the grade IV group. According to multivariate analysis of all CCA patients, predictors of OS were: age, gender, year of diagnosis, marital status, race, grade, stage, and primary tumor site (P < 0.001). The OS of all CCA patients during the period 2008 to 2016 was significantly higher than that from 2000 to 2007 (P < 0.001). Conclusions: The incidence of CCA and survival of these patients improved over time. In particular, the highest increases were reported for grade IV CCA, which may be due to an earlier diagnosis and improved treatment.

Magnetic resonance imaging-based radiomics signature for preoperative prediction of Ki67 expression in bladder cancer.

PURPOSE: The Ki67 expression is associated with the advanced clinicopathological features and poor prognosis in bladder cancer (BCa). We aimed to develop and validate magnetic resonance imaging (MRI)-based radiomics signatures to preoperatively predict the Ki67 expression status in BCa. METHODS AND MATERIALS: We retrospectively collected 179 BCa patients with Ki67 expression and preoperative MRI. Radiomics features were extracted from T2-weighted (T2WI) and dynamic contrast-enhancement (DCE) images. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (low Ki67 expression group) in the training set. Minimum redundancy maximum relevance was used to identify the best features associated with Ki67 expression. Support vector machine and Least Absolute Shrinkage and Selection Operator algorithms (LASSO) were used to construct radiomics signatures in training and SMOTE-training sets, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. The decision curve analyses (DCA) and calibration curve and were used to investigate the clinical usefulness and calibration of radiomics signatures, respectively. The Kaplan-Meier test was performed to investigate the prognostic value of radiomics-predicted Ki67 expression status. RESULTS: 1218 radiomics features were extracted from T2WI and DCE images, respectively. The SMOTE-LASSO model based on nine features achieved the best predictive performance in the SMOTE-training (AUC, 0.859; accuracy, 80.3%) and validation sets (AUC, 0.819; accuracy, 81.5%) with a good calibration performance and clinical usefulness. Immunohistochemistry-based high Ki67 expression and radiomics-predicted high Ki67 expression based on the SMOTE-LASSO model were significantly associated with poor disease-free survival in training and validation sets (all P < 0.05). CONCLUSIONS: The SMOTE-LASSO model could predict the Ki67 expression status and was associated with survival outcomes of the BCa patients, thereby may aid in clinical decision-making.

CALD1 promotes the expression of PD-L1 in bladder cancer via the JAK/STAT signaling pathway.

BACKGROUND: Bladder cancer (BC) is a common malignant neoplasm with a high rate of recurrence and progression, despite optimal treatment. There is a pressing need to identify new effective biomarkers for the targeted treatment of BC. METHODS: The key gene CALD1 was screened via weighed gene co-expression network analysis (WGCNA) from encoding protein genes of BC. Clinical and prognostic significance was explored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell chamber experiment and nude mouse xenograft assay were performed to test cell growth, apoptosis, migration, invasion and tumorigenesis capacities. Immune correlation was analyzed in The Tumor Immune Estimation Resource (TIMER) database. Relevant signaling pathways were explored using gene set enrichment analysis (GSEA). RESULTS: Increased expression of CALD1 was significantly correlated with histological grade, clinical stage, T stage, and lymphatic metastasis. Kaplan-Meier survival curves showed that high CALD1 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in TCGA database, and with poor OS in the four GEO databases. CALD1 promotes growth, migration, invasion, and cell cycle of tumor cell, and inhibits tumor cell apoptosis in vitro and in vivo. CADL1 expression was positively correlated with increased CD274 levels (r=0.357, P=9.71e-14). JAK/STAT signaling pathway was significantly enriched in the high CALD1 expression group. CALD1-mediated PD-L1 overexpression (OE) was via the activation of the JAK/STAT signaling pathway; this effect was blocked by the specific JAK inhibitor Ruxolitinib. CONCLUSIONS: CALD1 is a potential molecular marker associated with prognosis. It promotes the malignant progression of BC and upregulates the PD-L1 expression via the JAK/STAT signaling pathway.

Hsa_circ_0004296 inhibits metastasis of prostate cancer by interacting with EIF4A3 to prevent nuclear export of ETS1 mRNA.

BACKGROUND: Circular RNAs (circRNAs) have been shown to play vital biological functions in various tumors, including prostate cancer (PCa). However, the roles of circRNAs in the metastasis of PCa remain unclear. In the present study, differentially expressed circRNAs associated with PCa metastasis were screened using high-throughput RNA sequencing, from which hsa_circ_0004296 was identified. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of circ_0004296 in PCa tissues and adjacent normal tissues as well as in blood and urine. Gain and loss of function experiments were performed to investigate the function of circ_0004296 in PCa. Bioinformatics analyses, RNA pull-down assay, and mass spectrometry were conducted to identify RNA-binding proteins. RNA immunoprecipitation and RNA and protein nuclear-cytoplasmic fractionation were performed to investigate the underlying mechanism. A xenograft mouse model was used to analyze the effect of circ_0004296 on PCa growth and metastasis in vivo. RESULTS: The expression of circ_0004296 was decreased in PCa tissues, blood, and urine, which was negatively associated with metastasis. Furthermore, gain and loss of function experiments in vitro and in vivo showed that circ_0004296 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of PCa cells. Mechanistically, circ_0004296 regulated host gene ETS1 expression at the post-transcriptional level. EIF4A3 was identified and confirmed as the downstream binding protein of circ_0004296. EIF4A3 expression was significantly upregulated in PCa tissues and associated with PCa metastasis. Silencing EIF4A3 suppressed PCa cell proliferation, migration, invasion, and EMT. CONCLUSIONS: Circ_0004296 overexpression efficiently inhibited ETS1 mRNA nuclear export by promoting EIF4A3 retention in the nucleus, leading to the downregulation of ETS1 expression and suppression of PCa metastasis; thus, circ_0004296 might be a potential biomarker and therapeutic target for patients with PCa.

Can Smoking Cause Differences in Urine Microbiome in Male Patients With Bladder Cancer? A Retrospective Study.

BACKGROUND: Tobacco smoking is a carcinogen for many cancers including bladder cancer. The microbiota is involved in the occurrence, development, and treatment of tumors. We explored the composition of male urinary microbiome and the correlation between tobacco smoking and microbiome in this study. METHODS: Alpha diversity, principal component analysis (PCA) and Adonis analysis, linear discriminant analysis (LDA) coupled with effect size measurement, and PICRUSt function predictive analysis were used to compare different microbiome between smokers and non-smokers in men. RESULTS: There were 26 qualified samples included in the study. Eleven of them are healthy controls, and the others are from men with bladder cancer. Simpson index and the result of PCA analysis between smokers and non-smokers were not different (P > 0.05) in healthy men. However, the abundance of Bacteroidaceae, Erysipelotrichales, Lachnospiraceae, Bacteroides, and so on in the urinary tract of smokers is much higher than that of non-smokers. Compared to non-smokers, the alpha diversity in smokers was elevated in patients with bladder cancer (P < 0.05). PCA analysis showed a significant difference between smokers and non-smokers (P < 0.001), indicating that tobacco smoking plays a vital role in urinary tract microbial composition. CONCLUSION: The composition of microbiome in the urinary tract is closely related to tobacco smoking. This phenomenon is more significant in patients with bladder cancer. This indicates tobacco smoking may promote the occurrence and development of bladder cancer by changing urinary tract microbiome.

Systemic immune-inflammation index predicts prognosis of bladder cancer patients after radical cystectomy.

BACKGROUND: The systemic immune-inflammation index (SII) has been used as a prognostic marker for several cancer types, but there is no in-depth study in bladder cancer. This study evaluated the potential utility of the SII as a prognostic factor in patients with bladder cancer after radical cystectomy. METHODS: A retrospective analysis of 209 patients with bladder cancer who had undergone radical cystectomy and were randomized into primary (N=139) and validation (N=70) cohorts was conducted. The overall survival (OS) was calculated using the Kaplan-Meier survival curves. The prognostic value of the SII in primary and validation cohorts were analyzed by using the Cox regression model. A SII-based nomogram for bladder cancer was produced in R software. RESULTS: A high SII (>507) was associated with poor prognosis in bladder cancer patients. Univariate and multivariate analyses revealed that the SII was an independent predictor for OS. The SII emerged as an independent prognostic factor that provided more accurate prognostic prediction than neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR), in the primary and validation cohorts. The nomogram had better accuracy and discrimination than tumor, lymph node, metastasis (TNM) classification. The concordance index values of nomogram were 0.82 for the primary cohort and 0.784 for the validation cohort. CONCLUSIONS: The SII can serve as an independent predictor of OS in patients who have undergone radical cystectomy for bladder cancer, and was found to be a better predictor of prognosis than NLR, PLR, and CAR. The nomogram is a reliable model for predicting postoperative OS of patients after radical cystectomy.

Bronchial injuries: a tale of differing presentations.

Bronchial disruptions are uncommon but nevertheless grievous injuries and are usually secondary to major thoracic trauma. Although many are associated with other catastrophic injuries causing early mortality, their presentations can be late and they are often difficult to diagnose. Their management is frequently challenging and the ideal course of treatment is not yet clearly defined. Here, we describe two cases of main bronchial injuries presenting to us with post-traumatic collapse lung, albeit with a widely differing post-trauma course. Both required thoracotomy followed by a resection and anastomosis of the disrupted/stenotic segment. Operative results were good with both cases showing a well-expanded lung and no postoperative anastomotic site stenosis during the period of follow-up. Our experience highlights that patients with major bronchial injuries can have varying presentations. High degree of suspicion is necessary for early diagnosis and prompt surgical treatment. Resection of the stenosed/fibrosed segment followed by anastomosis yields good results.

MicroRNA-340 inhibits invasion and metastasis by downregulating ROCK1 in breast cancer cells.

MicroRNAs (miRNAs/miRs) are 19-25 nucleotide-long, non-coding RNAs that regulate the expression of target genes at the post-transcriptional level. In the present study, the role of miR-340 in breast cancer (BC) was investigated. The overexpression of miR-340 significantly inhibited the proliferation, migration and invasion of human breast MDA-MB-231 cancer cells in vitro. The Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) gene was identified as a target of miR-340; its expression was downregulated by overexpression of miR-340 by binding to its 3'-untranslated region. The short interfering RNA-mediated silencing of ROCK1 was also performed, which phenocopied the effects of miR-340 overexpression. An inhibitor of miR-340 was used to suppress miR-340 expression, which led to increased expression of ROCK1, thus improving the proliferation, migration and invasion of MDA-MB-231 cells. Data from the present study suggest that miR-340 inhibits MDA-MB-231 cell growth and its downregulation may lead to the progression and metastasis of BC. Thus, miR340 may act as a tumor-suppressor agent that could serve a key role in the diagnosis and therapy of BC.

Inhibition of RAB1A suppresses epithelial-mesenchymal transition and proliferation of triple-negative breast cancer cells.

RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real­time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

miR-135b, upregulated in breast cancer, promotes cell growth and disrupts the cell cycle by regulating LATS2.

Dysregulation of microRNAs (miRNAs) plays a critical role in cancer progression. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-135b in breast cancer and to validate whether miR-135b could regulate proliferation of breast cancer cells by effecting specific targets in the Hippo pathway. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to quantify the expression levels of miR-135b in both breast cancer tissues and cell lines. To characterize the function of miR-135b, MTT assays, colony formation assays, cell migration assays, cell invasion assays, and cell cycle assays were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-135b, in corroboration with western blot assays. Finally, we verified the changes of cellular function after transfection of LATS2-siRNA. Our experiments indicate that expression of miR-135b was commonly upregulated in breast cancer specimens and breast cancer cells when compared with that in adjacent normal tissues and non-malignant breast epithelial cells. Enforced expression of miR-135b can regulate cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-135b directly bound to the 3'-untranslated region (3'-UTR) of LATS2 (large tumor suppressor kinase 2), a critical gene in the Hippo pathway. Western blot analysis verified that miR-135b regulated the expression of LATS2 at protein levels. Further study demonstrated that the downstream gene of LATS2 in the Hippo pathway, such as cyclin-dependent kinase 2 (CDK2) and Phospho-Yes-associated protein (p-YAP), can also be regulated by miR-135b and LATS2 axis. Knockdown of endogenous LATS2 can mimic the result of miR-135b up-regulation in breast cancer. Taken together, our findings reveal that the miR-135b and LATS2 axis may be a potential therapeutic target for breast cancer in the future.

MicroRNA-96 plays an oncogenic role by targeting FOXO1 and regulating AKT/FOXO1/Bim pathway in papillary thyroid carcinoma cells.

MicroRNAs (miRNAs) are kind of small non-coding RNAs that negatively regulate gene expression at post-transcription level, and those non-coding RNAs appear to play a key role in tumorigenesis. The aim of this study was to investigate the biological role of miR-96 in papillary thyroid carcinoma (PTC) cell lines. We identified miR-96 to be up-regulated in PTC specimens in comparison to matched normal tissues by microRNA microarray and RT-qPCR analysis (P < 0.05). Next, to explore the potential function of miR-96, PTC cell lines K1 and TPC1 were transiently transfected with miR-96 mimics and inhibitor. Successful transfection being confirmed by RT-qPCR. Ectopic expression of miR-96 promoted proliferation and colony formation ability, and inhibited apoptosis of K1 and TPC1 cells, whereas down-regulated expression of miR-96 suppressed those functions when compared with the control cells. According to a computational prediction, FOXO1 maybe a potential target of miR-96. Luciferase assays revealed that miR-96 is directly targeted to both binding sites of FOXO1 3'-untranslated region (3'-UTR) and suppressed the FOXO1 expression, and subsequently inhibited the expression of Bim protein in PTC cells. Moreover, the expression of FOXO1 had an inverse correlation with expression of miR-96 in PTC specimens by RT-qPCR and western blot analysis. The data from the present study demonstrated that miR-96 can promote proliferation, and inhibit apoptosis in PTC cell lines K1 and TPC1, thus miR-96 may play an oncogenic role in PTC by inhibiting the FOXO1 and regulating AKT/FOXO1/Bim pathway, and it may serve as a novel therapeutic target for miRNA-based PTC therapy.

Comparison of Fine Needle Aspiration and Fine Needle Nonaspiration Cytology of Thyroid Nodules: A Meta-Analysis.

BACKGROUND: Fine needle aspiration cytology (FNAC) and fine needle nonaspiration cytology (FNNAC) are useful cost-effective techniques for preoperatively assessing thyroid lesions. Both techniques have advantages and disadvantages, and there is controversy over which method is superior. This meta-analysis was performed to evaluate the differences between FNAC and FNNAC for diagnosis of thyroid nodules. METHODS: Primary publications were independently collected by two reviewers from PubMed, Web of Science, Google Scholar, EBSCO, OALib, and the Cochrane Library databases. The following search terms were used: fine needle, aspiration, capillary, nonaspiration, sampling without aspiration, thyroid, and cytology. The last search was performed on February 1, 2015. RESULTS: Sixteen studies comprising 1,842 patients and 2,221 samples were included in this study. No statistically significant difference was observed between FNAC and FNNAC groups with respect to diagnostically inadequate smears, diagnostically superior smears, diagnostic performance (accuracy, sensitivity, specificity, negative predictive value, and positive predictive value), area under the summary receiver operating characteristic curve, average score of each parameter (background blood or clot, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and retention of appropriate architecture), and total score of five parameters. CONCLUSION: FNAC and FNNAC are equally useful in assessing thyroid nodules.