Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p<0.001). Combined with multiple clinical pathological factors, the results of multivariate analyses confirmed that this signature was an independent predictor of OS (HR, 3.548; 95%CI, 2.096−6.006; p<0.001). The results of immune infiltration analysis demonstrated that the abundance of multiple tumor-infiltration lymphocytes such as CD8+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.
Objectives: We evaluated differences in cytokine responses and T-lymphocyte subsets following retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal cell carcinoma (RCC). Methods: A total of 62 patients with T 1 N 0 M 0 staged RCC were randomized to either retro-laparoscopic (n = 31) or open (n = 31) radical nephrectomy. Plasma levels of interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-alpha (TNF-α) were measured separately by enzyme linked immunosorbent assay (ELISA) preoperatively and on postoperative days 1 and 5. Levels + in the open group, returned to about preoperative levels (p < 0.05). Follow-up ranged from 4 to 14 months postoperatively in all 62 patients with a 100% cancerspecific survival rate in both groups. Conclusions: Retroperitoneal laparoscopic radical nephrectomy is associated with the milder cytokine responses caused by trauma and inflammation and the better preserved distribution of T-lymphocytes. IntroductionSince Clayman and colleagues in 1991 1 reported the first laparoscopic radical nephrectomy (LRN) for a tumour-bearing kidney, this technique has become increasingly popular because of milder postoperative pain, decreased hospital stay and shortened convalescence compared to the conventional open radical nephrectomy (ORN). During the last 20 years, with advances in instrumentation and surgeon experience, LRN has emerged as an equally effective and minimally morbid surgical alternative to ORN for selected kidney neoplasms. 2,3Surgical trauma provokes a variety of physiologic and immunologic changes in the host. The host's acute phase response to injury includes a complicated interaction among the metabolic, neuroendocrine and immune systems. This response is deemed to be proportional to the extent of the initial injury and is presumably directed toward the host defense. 4 Due to this altered immune response in the postoperative period, surgical trauma can cause an increased production of pro-inflammatory cytokines and an inhibition of cellular responses.5 A wealth of studies with intermediate to long-term follow-up results indicate that laparoscopic radical malignance resections offer equivalent safety and oncologic efficacy as compared to open surgical approaches.6,7 This is partially because of the reduced inflammatory response and minimal extent of immunosuppression. However, some authors have reported no evidence of improved immunity after laparoscopy. [8][9][10][11] In addition, port site metastases (PSM) and local recurrences, although occasionally observed, remain a disputable problem with laparoscopic surgery for cancer. 12,13 With respect to renal cell carcinoma (RCC), laparoscopy related studies on the host immunity are insufficient and incomplete. Whether and how the laparoscopy under CO 2 pneumoperitoneum could exert some negative influences on the RCC patients is still unclear.
Background: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains controversial. In addition, several unanswered questions regarding the use of CN remain: Can CN provide survival benefits for patients with mRCC? Where do we place CN in the treatment sequence paradigm among patients with mRCC? How do we best stratify patients with mRCC for CN therapy? Materials and Methods: A search strategy was conducted in the PubMed, Embase, and Web of Science databases. Studies were included only in the English language. The risk of bias assessment was made by using ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) and RoB 2 (Risk of Bias 2) tools. The expected outcomes were analyzed by meta-analyses with the fixed-effects model or random effects model, including overall survival (OS) and progression-free survival (PFS). The measure of effect was the hazard ratio (HR) with a 95% CI, and sensitivity analysis was conducted to assess the reliability of the final results. Results: A total of 30 studies were included in the qualitative analysis. The HR for OS was 0.55 (95% CI, 0.50–0.61), and PFS was 0.72 (95% CI, 0.66–0.80), favoring CN compared with no CN. The upfront CN plus targeted therapy (TT) group had superior OS (HR, 0.57; 95% CI, 0.51–0.64) compared with the TT alone group. Furthermore, upfront CN plus systemic therapy (ST) was associated with numerically inferior OS compared with ST plus deferred CN in patients with mRCC (HR, 1.31; 95% CI, 0.98–1.74). Finally, the leave-one-out test of sensitivity analysis indicated that the results of this meta-analysis were stable and reliable in the overall HR estimates for these survival outcomes. Conclusions: First, CN was associated with better survival than no CN in patients with mRCC. Second, the combination of upfront CN and TT may lead to superior survival outcomes compared to TT alone in patients with mRCC. Survival outcomes were similar between the upfront CN+ST group and the ST+deferred CN group in patients with mRCC. Exact patient selection based on baseline prognostic factors is needed to promise maximal survival for patients with mRCC.
Obejectives: To evaluate the clinical characteristics and prognostic factors of Nonseminomatous Germ Cell Tumor (NSGCT). Patients and methods: Testicular cancer (TC) survey was conducted by Department of Urology, West China Hospital from 2008 to 2018. Details such as age, tumor size, tumor markers, histopathology, clinical stage, initial treatment, follow up, and clinical outcomes were provided by the database of our center. Tumor stage was classified according to the NCCN criteria(1). Results: Orchiectomy, chemotherapy and radio-therapy were the main treatments for these patients. Clinical stage I, stage II and stage III patients accounted for 74.6% (150), 7.5% (15) and 17.9% (36), respectively. After a median follow up time of 63 months, 4 patients relapsed during observation and 3 of them died. 4 patients died because of advanced malignancies. Among CSI patients, 2 relapsed and 1 died in 3 months after orchiectomy. No recurrence was found in CSII patients. 2 out of 29 stage III cases relapsed after treatment and 3 died of advanced cancer. The 3- and 10- year OS was 95.6% and 88.7%, respectively. For all the patients, the 3- and 10-year PFS was 94.9% and 88.8%. According to our data, we found that the meatastasis and tumor size were risk factors for NSGCTs. Conclusion: The present report showed a good prognosis at non-metastatic stage(CSI). However, the prognosis of advanced disease(CSII and CSIII) is significantly worse than that of early stage. We also found that maximum tumor diameter of >5cm was a potential risk factor for NSGCT.
Background: Immune and stromal cells in the tumor microenvironment have exhibit critical relevance with tumorigenesis and progression. Therefore, our analysis was conducted to explore the potential prognostic factors and the therapeutic targets of bladder cancer (BC) that affiliate to immune and stromal infiltration signature.Methods: Immune and stromal score were calculated for BC patients from TCGA database using ESTIMATE algorithm to predict the level of infiltration. Kaplan-Meier curves were utilized to assess the correlation of immune/stromal infiltration with survival outcomes. Differential expression genes (DEGs) were identified. Enrichment analyses, Kaplan-Meier curves, protein-protein interaction (PPI) network construction were performed to describe and screen the core module genes, whose prognostic value was further validated by an independent GEO dataset. Transcriptional factors (TFs) and ncRNA. correlated with the core module were identified using RAID 2.0 and TRRUST 2.0 database, and drugs potentially regulative for BC were accordingly screened using DrugBank.Results: 393 and 93 BC patients were enrolled from TCGA and GEO respectively. Higher stromal infiltration indicated worse overall survival (P = 0.015), and higher immune infiltration indicated an improvement on overall survival (P = 0.042). 562 DEGs were identified and 123 of them associated with survival outcomes. PPI has identified the core module genes, in which EFNB2 was the only core prognostic gene that was validated by both TCGA (P = 0.042) and GEO dataset (P = 0.036). Four TFs and Five ncRNAs (e.g. HIF1A) were associated with the regulation of the core module genes, and six drugs were screened as potential candidates to regulate BC.Conclusion: Higher immune infiltration in bladder tumor was correlated with improved survival and higher stromal infiltration corelated with worse survival. Furthermore, a higher expression of EFNB2 was tied with poorer prognosis of BC, which was validated by two independent datasets.
Background: Phthalates are chemical substances widely used in human consumer goods. Studies have shown that phthalates exposure can affect the physiological function of estrogen receptor (ER). However, there is no comprehensive discussion on the association between phthalates exposure and ER-related cancer risk.Objective: We conducted a cross-sectional study of urinary phthalate metabolite concentrations and self-reported ER-related cancers among 3,015 participants from two cycles of the national health and Nutrition Examination Survey (NHANES), 2003-2006.Methods: Seven compounds of phthalate metabolites were examined as expoure biomarkers. We used multivariate logistic regression to estimate odds ratio (ORs) and 95% confidence intervals (CIs), adjusting for potential confounding factors. The concentration of phthalate metabolites is non-normal distribution, so quantile and log-transformation are used for analysis. Account for urine dilution, the creatinine corrected phthalate concentration was applied in our analysis. In addition, we also conducted sensitivity analysis by gender stratification and trend test to explore whether there is a concentration increase effect, so as to explore the relationship between these seven phthalate metabolites and the risk of ER-related cancers.Results: We observed a higher prevalence of ER-related cancers in the maximal quantile of MCNP (OR=2.37; 95%Cl=1.01-5.55) in adjusted model. Meanwhile, trend test also confirmed that MCNP had a positive trend with the risk of ER-related cancer (P=0.036). In subgroup analysis, the higher concentration of MCNP, the higher the risk of breast cancer. At the same time, the trend test verified our results: the results are positive (OR=3.68;95%Cl=1.15-11.74) (P=0.014).Conclusion: We provide the main evidence that urinary phthalate metabolites concentrations are positively correlated with ER-related cancers. The positive relationship between MCNP exposure and breast cancer risk is more obvious in women. Further causal studies are needed to confirm the findings in our analysis and clarify the underlying mechanisms.
Objective: As the population aged, voiding dysfunction has been steadily rising among males during the past decade. Increasing evidence showed that sleep disorders are associated with an increasing risk of various diseases, but the association between sleep disorders and lower urinary tract symptoms (LUTS) / benign prostatic hyperplasia (BPH) among Chinese males have not been well characterized.Methods: We conducted a cross-sectional analysis of data from West China Natural Population Cohort Study (WCNPCS) 2019-2021. Sleep quality was assessed by Pittsburgh sleep quality index (PSQI) in Chinese version. LUTS/BPH as a dependent variable of a binary variable, assessed by a self-reported questionnaire. Multivariate logistic regression analysis were performed to evaluate the correlation between sleep disorders and the risk of LUTS/BPH after adjusting for confounding factors.Results: 11,824 eligible Chinese men participated in this cross-sectional survey. In multivariate logistic regression analysis, after adjusting for confounding variables, global PSQI score (OR: 1.257, 1.119-1.411, p<0.001) and its six compounds (Subjective sleep quality: OR: 1.376, 1.004-1.886, p=0.048; Sleep latency: OR: 0.656, 0.557-0.773, p<0.001; Sleep duration: OR:1.441, 1.189-1.745, p<0.001; Habitual sleep efficiency: OR: 1.369, 1.193-1.570, p<0.001; Daytime dysfunction: OR: 1.702, 1.278-2.267, p<0.001) except the use of sleep drug subgroup were significantly positively correlated with LUTS/BPH prevalence. Significant interaction effects were observed in age subgroups (age-young group: age<51; age-middle group: 51≤age≤61; age-older group: age>61) (P < 0.05). Among older participants, sleep disorders were more significantly associated with the risk of LUTS/BPH.Conclusions: There was a significant association between poor sleep quality and increased prevalence of LUTS/BPH, especially among the elderly male population, suggesting an important role of healthy sleep in reducing prostate disease burden.
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