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Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma (UC). To evaluate the predictive and prognostic value of PD-L1 on response and survival in UC patients after cystectomy, chemotherapy, or anti-PD-1/PD-L1 therapy, a systematic review of PubMed, Embase, Web of Science, and the Cochrane Library was performed. A total of 2154 patients from 14 published studies were included. In all UC patients after cystectomy, tumour cell (TC) PD-L1 expression was not associated with the OS or PFS. For the subset of patients with organ-confined disease, TC PD-L1 expression significantly predicted OS after cystectomy (P = 0.0004). There was no significant evidence of an association between TC PD-L1 status and ORR or OS for UC patients treated with platinum-based chemotherapy. For UC patients treated with anti-PD-1/PD-L1 therapy, TC PD-L1 expression ≥ 5 % could predict the response (P = 0.005), but not for the 1% cut-off (P ≥ 0.05). As for PD-L1 expression in tumour-inflating immune cells (TIICs), both subsets with IC2/3 vs. IC0/1 and IC1/2/3 vs. IC0 were associated with ORR to anti-PD-1/PD-L1 therapy. In the TIIC subset, IC2/3 vs. IC0/1 of PD-L1 was associated with higher CR (P = 0.002), PR (P = 0.04), and PD (P = 0.007). Further, higher TIIC PD-L1 status benefited from longer PFS (P < 0.001), but was not associated with OS in UC patients with anti-PD-1/PD-L1 therapy. Our study suggested that TIIC PD-L1 expression with 5% cut-off was valuable as a predictive and prognostic biomarker for ORR and PFS in UC patients with anti-PD-1/PD-L1 therapy. [ABSTRACT FROM AUTHOR]

Background. Inducible nitric oxide synthase (iNOS) is confirmed to regulate the production of nitric oxide (NO) when cells are exposed to external stimulus. Recent publications revealed that overexpression of iNOS predicted poor clinical outcomes for patients with malignant cancers, e.g., gastric, bladder, and colorectal cancers; however, several studies reported no obvious relationship between iNOS expression and prognosis of solid tumors. The aim of our study was to investigate the pooled effect of the prognostic value of iNOS expression. Materials and Methods. We performed a systematic search of PubMed, Web of Science, and Embase databases up to January 15, 2019. The concerned outcomes of interest included overall survival (OS), cancer-special survival (CSS), and recurrence-free survival (RFS). Results. Fourteen studies with 1,758 patients were included in this meta-analysis, and we reached the conclusion that increased iNOS expression was significantly associated with worse OS (HR: 1.89, 95% CI: 1.57 - 2.28, p ≤ 0.001), worse CSS (HR: 3.13, 95% CI: 1.88 - 5.20, p ≤ 0.001), and worse RFS (HR: 2.16, 95% CI: 1.29 - 3.62, p = 0.003) in solid tumors. Furthermore, the subgroup analysis identified the significant relationship of high iNOS expression with poor OS in gastric cancer. No obvious publication bias was detected by Begg's tests. Conclusion. In summary, the results drawn in our meta-analysis demonstrated that elevated expression of iNOS had a significant association with poor survival in human cancer. iNOS might serve as a promising predictive biomarker of prognosis in cancer patients, and well-designed prospective studies are further needed to substantiate the prognostic value of iNOS. [ABSTRACT FROM AUTHOR]

Background. As a newly discovered lncRNA, bladder cancer-associated transcript 1 (BLACAT1) has been reported to correlate with poor clinical outcomes in several different cancers. This study aimed to evaluate its generalized predictive value for cancer prognosis. Materials and Methods. We thoroughly searched PubMed, Embase, and Web of Science databases for eligible studies published until November 11, 2018, in which the relationship between BLACAT1 expression and cancer prognosis was explored. The analyses were performed using Review Manager Version 5.3 and Stata SE 12.0. The primary endpoints included overall survival (OS), pathological characteristics (TNM stage and tumor grade), lymph node metastasis (LNM), and distant metastasis. Results. Ten studies containing 861 patients with 7 different cancerous diseases were eventually included. The results demonstrated that patients with high lncRNA BLACAT1 expression had a significantly shorter OS (HR: 1.82, 95% CI: 1.44-2.30, p < 0.00001) than patients with low lncRNA BLACAT1 expression. Moreover, elevated BLACAT1 expression was significantly associated with advanced TNM stage (OR: 2.29, 95% CI: 1.15-4.56, p = 0.005), high tumor grade (OR: 1.67, 95% CI: 1.11-2.53, p = 0.01), and lymph node metastasis (OR: 2.53, 95% CI: 1.80-3.57, p < 0.00001). Meanwhile, the expression of BLACAT1 had no significant association with age (p = 0.92), gender (p = 0.55), and smoking (p = 0.62). Conclusion. High expression of lncRNA BLACAT1 may predict a poor prognosis in OS, TNM stage, tumor grade, and LNM. Its predictive roles were not significantly affected by age, gender, or smoking. Therefore, lncRNA BLACAT1 may serve as a promising predictor in cancer prognosis. [ABSTRACT FROM AUTHOR]