SLAMF7 predicts prognosis and correlates with immune infiltration in serous ovarian carcinoma.

OBJECTIVE: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). METHODS: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). RESULTS: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cell-specific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). CONCLUSION: SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC. Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

[Modified sandwich urethral reconstruction in laparoscopic radical prostatectomy improves early recovery of urinary continence].

OBJECTIVE: To explore the safety of modified sandwich urethral reconstruction (MSUR) in laparoscopic radical prostatectomy (LRP) and its effect on the early recovery of urinary continence. METHODS: We retrospectively analyzed the clinical data on 20 patients treated by LRP with MSUR (the MSUR group) and another 21 cases of LRP without MSUR (the conventional control group) from January 2018 to September 2019. We compared the two groups of patients in the general data, anastomosis time, operation time and urinary continence recovery. RESULTS: There were no statistically significant differences between the two groups of patients in the age, body mass index, Gleason scores, prostate volume and baseline PSA level (P > 0.05) or in operation time, intraoperative blood loss, drainage tube indwelling time, postoperative feeding time and postoperative hospital stay (P > 0.05). Anastomotic stenosis occurred in 1 case in the MSUR group postoperatively, which was cured after regular urethral dilation, and anastomotic fistula developed in 1 case in the control group, which was healed after 5 days of prolonged catheterization. The recovery rate of urinary continence at 12 weeks after catheter removal was significantly higher in the MSUR than in the control group (80.0% vs 47.6%, P < 0.05). CONCLUSIONS: Modified sandwich urethral reconstruction in LRP is a safe, effective and feasible surgical strategy, which can significantly improve postoperative urinary continence recovery of the patient.

Tumor-associated macrophages promote prostate cancer progression via exosome-mediated miR-95 transfer.

Tumor-associated macrophages (TAMs) are vital constituents in mediating cell-to-cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of "onco-vesicles" is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP-1 and M2 macrophages and found a significant increase in miR-95 levels in TAM-derived exosomes, demonstrating the direct uptake of miR-95 by recipient PCa cells. In vitro and in vivo loss-of-function assays suggested that miR-95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial-mesenchymal transition. The clinical data analyses further revealed that higher miR-95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM-mediated PCa progression is partially attributed to the aberrant expression of miR-95 in TAM-derived exosomes, and the miR-95/JunB axis provides the groundwork for research on TAMs to further develop more-personalized therapeutic approaches for patients with PCa.

Does exposure to asbestos cause prostate cancer? A systematic literature review and meta-analysis.

OBJECTIVE: The relationship between asbestos and prostate cancer (PCa) is not well understood due to small number of cases. This study aimed to determine the incidence and mortality of PCa among workers or residents exposed to asbestos based on a systematic review and meta-analysis METHODS: All published studies citing the standardized mortality ratio (SMR) or standardized incidence ratio (SIR) of PCa in workers or residents exposed to asbestos were collected by conducting a search on PubMed, EMBASE, Cochrane Library, and Web of Science before April 2018. Standardized mortality rate for PCa with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA (Version14.0). This study is registered with PROSPERO, number CRD42018095195. RESULTS: A total of 17 independent studies were included for the analysis. The overall pooled SMR of PCa was 1.22, with a 95% CI of 1.13 to 1.32, with no heterogeneity across the studies (I = 18.8%, P = .234). Subgroup analysis shows that exposure to crocidolite, cement, studies conducted in Europe and Oceania, and long study follow-up (≥25 years) all contribute to significantly higher SMR, and we found no evidence of publication bias (Begg test P value = .592, Egger test P value = .874). CONCLUSIONS: This meta-analysis suggested that exposed to asbestos might be associated with an increased risk of PCa. High-exposure level of asbestos could contribute to significantly higher risk of PCa mortality.

Clinical significance of MACC1, Twist1, and KAI1 expressions in infiltrating urothelial carcinoma of the bladder.

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1), a candidate oncogene, promotes tumor cell invasion and metastasis in various cancers. Twist1, a key transcriptional gene of the epithelial-mesenchymal transition (EMT), is involved in EMT and metastasis in many cancers. KAI1, also known as CD82, was originally considered as a suppressor gene of tumor metastasis. In this study, we investigated the expressions and significance of MACC1, Twist1, and KAI1 in infiltrating urothelial carcinoma of bladder (IUCB). METHODS: The expressions of MACC1, Twist1, and KAI1 in 195 IUCB specimens and their corresponding control specimens were investigated by immunohistochemistry. The patients' clinical, demographic, and follow-up data were collected. RESULTS: The rates of the positive expressions of MACC1 and Twist1 were significantly higher in IUCB tissues than in normal bladder mucosa tissues, and their expressions were positively correlated with tumor stages, grades of differentiation, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stages. The rate of positive expression of KAI1 was significantly lower in IUCB than in the control tissues, and its expression was inversely associated with tumor stages, grades of differentiation, LNM, and TNM stages. Patients who expressed MACC1 or Twist1 had an unfavorable overall survival (OS) time when compared with patients who did not express these proteins. However, patients who expressed KAI1 had a favorable OS when compared with patients who did not express this protein. A multivariate analysis demonstrated that the expressions of MACC1, Twist1, and KAI1, tumor stages, grades of differentiation, LNM, as well as TNM stages were independent prognostic indicators for IUCB patients. CONCLUSION: Therefore, MACC1, Twist1, and KAI1 should be considered potentially promising biomarkers of IUCB prognosis.

Centromere protein U is a potential target for gene therapy of human bladder cancer.

To investigate the role of centromere protein U (CENPU) in human bladder cancer (BCa), CENPU gene expression was evaluated in human BCa tissues. We used real-time quantitative PCR (qPCR) and found that CENPU gene expression in human BCa tissues was higher compared to that observed in cancer-adjacent normal tissues. High CENPU expression was found to be strongly correlated with tumor size and TNM stage. Kaplan-Meier survival analysis indicated that high CENPU levels were associated with reduced survival. We used a lentivirus to silence endogenous CENPU gene expression in the BCa T24 cell line. CENPU knockdown was confirmed by qPCR. Cellomic imaging and BrdU assays showed that cell proliferation was significantly reduced in the CENPU-silenced cells compared to that noted in the control cells. Flow cytometry revealed that in the CENPU-silenced cells the cell cycle was arrested at the G1 phase relative to that in the control cells. In addition, apoptosis was significantly increased in the CENPU-silenced cells. Giemsa staining showed that CENPU-silenced cells, compared to control cells, displayed a significantly lower number of cell colonies. The genome-wide effect of CENPU knockdown showed that a total of 1,274 differentially expressed genes was found, including 809 downregulated genes and 465 upregulated genes. Network analysis by Ingenuity Pathway Analysis (IPA) resulted in 25 distinct signaling pathways, including the top-ranked network: 'Cellular compromise, organismal injury and abnormalities, skeletal and muscular disorders'. In-depth IPA analysis revealed that CENPU was associated with the HMGB1 signaling pathway. qPCR and western blot analysis demonstrated that in the HMGB1 signaling pathway, CENPU knockdown downregulated expression levels of ILB, CXCL8, RAC1 and IL1A. In conclusion, our data may provide a potential pathway signature for therapeutic targets with which to treat BCa.

MicroRNA-542-3p suppresses cellular proliferation of bladder cancer cells through post-transcriptionally regulating survivin.

AIM: To investigate the clinical significance of microRNA-542-3p (miR-542-3p) and its target gene survivin in human bladder cancer, and to determine their functions in malignant phenotypes of this disease. METHODS: Expression levels of miR-542-3p and survivin mRNA in bladder cancer and adjacent normal tissues were detected by quantitative RT-PCR. Cell proliferation and cell cycle were assessed by cell viability assay, flow cytometry and colony formation assay based on two human bladder cancer cell lines. RESULTS: MiR-542-3p expression was downregulated, while survivin mRNA expression was upregulated in bladder cancer tissues, compared to adjacent normal tissues (both P<0.001). Importantly, the expression level of miR-542-3p in bladder cancer tissues was negatively correlated with that of survivin mRNA. MiR-542-3p-low and/or survivin-high expression were all significantly associated with tumor stage (all P<0.05) and tumor recurrence (all P<0.05) of patients with bladder cancer. Moreover, the enforced expression of miR-542-3p remarkably inhibited cell proliferation by inducing G1 phase arrest in both T24 and J82 cells, and decreased the expression level of survivin protein. In contrast, the knock-down of miR-542-3p dramatically promoted the proliferation of bladder cancer cells by accelerating the progression of cell cycle and increased the expression level of survivin protein. CONCLUSION: MiR-542-3p and its target gene survivin may play crucial roles in the aggressive progression of human bladder cancer. More interestingly, miR-542-3p may function as a tumor suppressor and inhibit the proliferation of bladder cancer cells, implying that miR-542-3p-survivin signal axis might be a novel therapeutic target of this disease.