BackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein–protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages.ConclusionThe expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.

We conducted a multicenter clinical study to construct a novel index based on a combination of albumin-globulin score and sarcopenia (CAS) that can comprehensively reflect patients' nutritional and inflammatory status and assess the prognostic value of CAS in renal cell carcinoma (RCC) patients. Between 2014 and 2019, 443 patients from 3 centers who underwent nephrectomy were collected (343 in the training set and 100 in the test set). Kaplan-Meier curves were employed to analyze the impact of albumin-globulin ratio (AGR), albumin-globulin score (AGS), sarcopenia, and CAS on overall survival (OS) and cancer-specific survival (CSS) in RCC patients. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of AGR, AGS, sarcopenia, and CAS on prognosis. High AGR, low AGS, and nonsarcopenia were associated with higher OS and CSS. According to CAS, the training set included 60 (17.5%) patients in grade 1, 176 (51.3%) patients in grade 2, and 107 (31.2%) patients in grade 3. Lower CAS was linked to longer OS and CSS. Multivariate Cox regression analysis revealed that CAS was an independent risk factor for OS (grade 1 vs. grade 3: aHR = 0.08; 95% CI: 0.01–0.58, p = 0.012; grade 2 vs. grade 3: aHR = 0.47; 95% CI: 0.25–0.88, p = 0.018) and CSS (grade 1 vs. grade 3: aHR = 0.12; 95% CI: 0.02–0.94, p = 0.043; grade 2 vs. grade 3: aHR = 0.31; 95% CI: 0.13–0.71, p = 0.006) in RCC patients undergoing nephrectomy. Additionally, CAS had higher accuracy in predicting OS (AUC = 0.687) and CSS (AUC = 0.710) than AGR, AGS, and sarcopenia. In addition, similar results were obtained in the test set. The novel index CAS developed in this study, which reflects patients' nutritional and inflammatory status, can better predict the prognosis of RCC patients.

Purpose: Evaluate the diagnostic accuracy of multi-parametric magnetic resonance imaging (mp-MRI) for local staging of bladder cancer (BCa).Materials and Methods: The databases of PubMed, Web of Science, Wanfang, and CNKI were searched for related literatures about BCa diagnosed by mp-MRI from January 1, 2000 to April 12, 2019. The strict inclusion and exclusion criteria were set up to extract records. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 was used to evaluate quality of the candidate studies. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (−LR), and diagnostic odds ratio (DOR) were calculated to assess the diagnostic authenticity of mp-MRI. The summarized receiver operating characteristic (SROC) curve corresponding with the area under the curve (AUC) were analyzed to comprehensively evacuate the diagnostic value of mp-MRI.Results: A total of 140 studies were retrieved by computer-based searching. After quality control, 4 studies with 259 patients were enrolled for meta-analysis. The pooled results showed 0.84 of sensitivity [95% confidence interval (CI) = 0.79-0.89], 0.91 of specificity (95% CI = 0.87–0.93), 8.24 of +LR (95% CI = 4.87–13.92), 0.18 of –LR (95% CI = 0.10–0.31), 49.42 of DOR (95% CI = 19.07–128.09), and 0.946 of AUC. The Spearman correlation analysis found no threshold effect (p = 0.684). A significant heterogeneity existed among 4 included studies with sensitivity (I2 = 65.7%), specificity (I2 = 60.0%) and diagnostic OR (I2 = 67.5%). The Begg's test (p = 0.497) and the egger's test (p = 0.337) found no publication bias.Conclusion: mp-MRI acts a good diagnostic performance for bladder cancer. It is plausible that mpMRIs can be used as an important method for bladder cancer staging.