Development and validation of cancer-associated fibroblasts-related gene landscape in prognosis and immune microenvironment of bladder cancer.

Backgrounds: Bladder cancer (BLCA) is one of the most prevalent cancers of the genitourinary system, the clinical outcomes of patients with BLCA are bad, and the morbidity rate is high. One of the key components of the tumor microenvironment (TME) is cancer-associated fibroblasts (CAFs) which are critically involved in BLCA tumorigenesis. Previous studies have shown the involvement of CAFs in tumor growth, cancer progression, immune evasion, angiogenesis, and chemoresistance in several cancers such as breast, colon, pancreatic, ovarian, and prostate cancers. However, only a few studies have shown the role of CAFs in the occurrence and development of BLCA. Methods: We have retrieved and merged the data on RNA-sequencing of patients with BLCA from databases including "the Cancer Genome Atlas" and "Gene Expression Omnibus." Next, we compared the differences in CAFs-related genes (CRGs) expression between normal and BLCA tissues. Based on CRGs expression, we randomly divided patients into two groups. Next, we determined the correlation between CAFs subtypes and differentially expressed CRGs (DECRGs) between the two subtypes. Furthermore, the "Gene Ontology" and "Kyoto Encyclopedia of Genes and Genomes pathway" enrichment analyses were conducted to determine the functional characteristics between the DECRGs and clinicopathology. Results: We identified five genes (POF1B, ARMCX1, ALDOC, C19orf33, and KRT13) using multivariate COX regression and "Least Absolute Shrinkage and Selection Operator (LASSO) COX regression analysis" for developing a prognostic model and calculating the CRGs-risk score. The TME, mutation, CSC index, and drug sensitivity were also analyzed. Conclusion: We constructed a novel five- CRGs prognostic model, which sheds light on the roles of CAFs in BLCA.

Inadvertent radical nephrectomy leads to worse prognosis in renal pelvic urothelial carcinoma patients: A propensity score-matched study.

Objective: To compare overall survival (OS) and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients treated with radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN). Patients and methods: In this retrospective study, patients with RPUC who underwent NU or RN diagnosed between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results database. To adjust the confounders, the propensity score-matched analysis was conducted. The Kaplan-Meier method and log-rank test were performed to explore the effect of different surgical methods on OS and CSS. Results: A total of 2197 cases were finally included in this analysis, among which, 187 (8.5%) patients were treated with RN and 2010 (91.5%) patients were treated with NU. Before matching, the survival analysis revealed that the OS (HR: 1.444, 95%CI: 1.197, 1.741) and CSS (HR: 1.522, 95%CI: 1.211, 1.914) of patients who received RN were worse than that of patients who received NU (p = 0.0001 and p = 0.0003, respectively). After matching, the RN group had a worse OS (HR: 1.298, 95%CI: 1.002, 1.682) than the NU group (p = 0.048). No significant difference was observed in CSS between the RN and NU groups (p = 0.282). The hierarchical analysis showed that there was no significant difference observed in OS and CSS in patients with tumor size ≤4.2 cm (p = 0.884 and p = 0.496, respectively). In tumor size >4.2 cm, both OS (HR: 1.545, 95%CI: 1.225, 1.948) and CSS (HR: 1.607, 95%CI: 1.233, 2.095) of patients who received RN were worse than those of patients who received NU (p = 0.0002 and p = 0.0005). Conclusion: RN could lead to worse oncological outcomes than NU in patients with renal pelvis urothelial carcinoma. Accurate diagnosis of renal pelvis urothelial carcinoma is extremely important.

Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-ß signaling pathway.

Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-ß pathway. Inhibition of the TGF-ß pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-ß pathway. This study may allow the development of novel approaches for PC.

[Primary non-Hodgkin's lymphoma of the testis and penis: clinical analysis of 5 cases].

OBJECTIVE: To improve the clinical diagnosis and treatment of primary non-Hodgkin's lymphoma of male genitalia. METHODS: We retrospectively reviewed the clinical data of 5 cases of primary non-Hodgkin's lymphoma of male genitalia, 4 in the testis and 1 in the penis, we also analyzed the relevant literature and clinical significance of the disease. RESULTS: All the 5 cases were treated by surgery and pathologically confirmed to be non-Hodgkin's lymphoma. Three of them received chemotherapy, and the other 2 (1 in the testis and 1 in the penis) underwent both chemotherapy and radiotherapy after the operation. Follow-up averaged 25 months, during which 1 of the patients died and the other 4 survived. CONCLUSION: Primary non-Hodgkin's lymphoma of male genitalia is an uncommon disease with atypical clinical presentations and poor prognosis, which occurs mostly in elderly males. Definite diagnosis of the disease mainly depends on histopathology and immunohistochemistry. Surgery with multiagent chemotherapy and radiotherapy is advisable for its treatment.