BackgroundCellular senescence plays crucial role in the progression of tumors. However, the expression patterns and clinical significance of cellular senescence-related genes in bladder cancer (BCa) are still not clearly clarified. This study aimed to establish a prognosis model based on senescence-related genes in BCa.MethodsThe transcriptional profile data and clinical information of BCa were downloaded from TCGA and GEO databases. The least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analyses were performed to develop a prognostic model in the TCGA cohort. The GSE13507 cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate underlying mechanisms.ResultsA six-gene signature (CBX7, EPHA3, STK40, TGFB1I1, SREBF1, MYC) was constructed in the TCGA databases. Patients were classified into high risk and low risk group in terms of the median risk score. Survival analysis revealed that patients in the higher risk group presented significantly worse prognosis. Receiver operating characteristic (ROC) curve analysis verified the moderate predictive power of the risk model based on the six senescence-related genes signature. Further analysis indicated that the clinicopathological features analysis were significantly different between the two risk groups. As expected, the signature presented prognostic significance in the GSE13507 cohort. Functional analysis indicated that immune-related pathways activity, immune cell infiltration and immune-related function were different between two risk groups. In addition, risk score were positively correlated with multiple immunotherapy biomarkers.ConclusionOur study revealed that a novel model based on senescence-related genes could serve as a reliable predictor of survival for patients with BCa.

Purpose: Controversy remains with using neoadjuvant chemotherapy (NAC) in patients with upper tract urothelial carcinoma (UTUC). Thus, we conducted a systematic review and meta-analysis of the peer-reviewed literature to assess the role of NAC in high-risk UTUC patients. Methods: PubMed, EMBASE, and the Cochrane Library were the main sources of relevant studies. The search terms included: “Upper urothelial carcinoma”; “UTUC”; “Urinary tract cancer”; and “Transitional cell carcinoma” combined with “Neoadjuvant chemotherapy” and “adjuvant chemotherapy”. We studied the relationship of UTUC and NAC. Overall survival, recurrent-free survival, cancer-specific survival and pathological response rate in patients treated with/without NAC before radical surgery were evaluated. Results: Five trials were selected, and included 532 participants. Each of the included studies was retrospective. The combined analysis showed that when compared to controls, the pooled hazard ratios of overall survival, recurrence-free survival and cancer-specific survival were 0.47 (95% confidence interval [CI], 0.34–0.64; P < .00001); 0.50 (95% CI, 0.37–0.66; P < .00001); and 0.37 (95% CI, 0.25–0.54; P < .00001), respectively. It indicates the beneficial effects of NAC for the prognosis of survival in UTUC. Additionally, NAC was significantly associated with T-stage down-grading (T3/4 to ≤T2; OR=7.58 [4.66, 12.33]; P < .0001) and pathological lymph node status (N+ to N0; OR = 6.24 [2.57,15.15]; P < .00001). Conclusions: NAC treatment before radical nephron-ureterectomy significantly improves survival prognosis in patients with high-risk upper tract urothelial carcinoma. However, considerable prospective and randomized studies are needed to confirm this perspective.

Obesity, the global pandemic since industrialization, is the number one lifestyle-related risk factor for premature death, which increases the incidence and mortality of various diseases and conditions, including cancer. In recent years, the theory of cancer stem cells (CSCs), which have the capacity for self-renewal, metastasis and treatment resistance, has been bolstered by increasing evidence. However, research on how obesity affects CSCs to facilitate cancer initiation, progression and therapy resistance is still in its infancy, although evidence has already begun to accumulate. Regarding the ever-increasing burden of obesity and obesity-related cancer, it is pertinent to summarize evidence about the effects of obesity on CSCs, as elucidating these effects will contribute to the improvement in the management of obesity-related cancers. In this review, we discuss the association between obesity and CSCs, with a particular focus on how obesity promotes cancer initiation, progression and therapy resistance through CSCs and the mechanisms underlying these effects. In addition, the prospect of preventing cancer and targeting the mechanisms linking obesity and CSCs to reduce cancer risk or to improve the survival of patients with cancer is considered.

cancer cell proliferation, migration and invasion. CCDC34 may serve as a biomarker or even a therapeutic target for bladder cancer.