Analysis of cell death-related genes to evaluate the prognostic and immunotherapeutic value in bladder cancer.

To enhance therapeutic approaches, we created a distinctive pattern utilizing the cell demise indicator (CDI) to predict the effectiveness of immunotherapy in individuals with bladder carcinoma (BLCA). Hub prognostic CDIs were identified from the TCGA database using differential gene expression and survival analysis, encompassing 763 genes across 13 death modes. The subtype assessment was employed to evaluate the impact of these genes on the prognosis and immunotherapeutic outcomes in patients with BLCA. The LASSO regression method was used to identify significant CDIs, while Cox regression and nomogram analyses were conducted to explore the impact of CDIs on prognosis. CHMP4C and GSDMB were selected as the hub genes for the following research. Subsequently, These two central genes underwent further investigation to explore their association with immunotherapy, followed by an analysis of their potential regulatory network. Subtype analysis showed that these CDIs were significantly associated with the prognosis and immunotherapy of BLCA patients. The regulatory network in BLCA was evaluated through the establishment of the lncRNA XIST/NEAT1-CDIs-miR-146a-5p/miR-429 axis. Immunohistochemical analysis revealed a significant up-regulation of CHMP4C in bladder cancer tissues, which was strongly associated with an unfavorable prognosis for BLCA patients. Moreover, our findings provide compelling evidence that CHMP4C plays a pivotal role in promoting BLCA progression through the activation of the epithelial-mesenchymal transition (EMT) pathway. These findings highlight the negative impact of CHMP4C on BLCA patient prognosis, while also providing insights into the oncogenic mechanisms and immunotherapy in which CHMP4C may be involved.

Targeting the prostate tumor microenvironment by plant-derived natural products.

Prostate cancer is among the most common malignancies for men, with limited therapy options for last stages of the tumor. There are some different options for treatment and control of prostate tumor growth. However, targeting some specific molecules and cells within tumors has been attracted interests in recent years. The tumor microenvironment (TME) has an important role in the initiation of various malignancies, which can also expand the progression of tumor and facilitate invasion of malignant cells. By regulating immune responses and distinct changes in the metabolism of cells in the tumor, TME has substantial effects in the resistance of cancer cells to therapy. TME in various solid cancers like prostate cancer includes various cells, including cancer cells, supportive stromal cells, immunosuppressive cells, and anticancer inflammatory cells. Natural products including herbal-derived agents and also other natural compounds have been well studied for their anti-tumor potentials. These compounds may modulate various signaling pathways involved in TME, such as immune responses, the metabolism of cells, epigenetics, angiogenesis, and extracellular matrix (ECM). This paper provides a review of the current knowledge of prostate TME and complex interactions in this environment. Additionally, the potential use of natural products and also nanoparticles loaded with natural products as therapeutic adjuvants on different cells and therapeutic targets within prostate TME will be discussed.

Preoperative White Blood Cell-Related Indicators Can Predict the Prognosis of Patients with Transurethral Resection of Bladder Cancer.

Introduction: Numerous studies, including bladder cancer (BLCA), have confirmed the relationship between conventional systemic inflammatory biomarkers and the prognosis of tumors. Leukocytes, as the most common factor in inflammatory indicators, have been reported to predict prognosis in other tumors. However, we have not seen this research in BLCA. Therefore, we aim to find new blood markers to predict the prognosis of patients with transurethral resection of bladder tumor (TURBT). Methods: Two cohorts from the two different hospitals were used for the specific study. The best cutoff values of leukocytes-related indicators were determined according to the ROC curve. Univariate and multivariate Cox regression analysis were used to explore the impact of indicators and clinical features on prognosis for patients with TURBT. The KM curve was used to show the impact of indicators on the prognosis. According to the consequence of multivariate method, a risk model was established to evaluate the prognosis of patients with bladder cancer. Results: The white blood cell-to-lymphocyte ratio (WLR), the white blood cell-to-hemoglobin ratio (WHR), the white blood cell-to-neutrophil ratio (WNR), the white blood cell-to-monocyte ratio (WMR) and the white blood cell-to-erythrocyte ratio (WRR) are related to the prognosis of BLCA. The new risk model consisted of WHR, WMR and platelet-to-lymphocyte ratio (PLR), and patients with TURBT in the high-risk group had a worse prognosis. Conclusions: Leukocyte-related preoperative indicators could predict the prognosis of the patients with TURBT and provided some guidance for clinical workers.

Clinical Significance of Nutrition and Inflammation in Esophageal Cancer Patients with Surgery: A Meta-Analysis.

Many studies have reported that the geriatric nutritional risk index (GNRI) and C-reactive protein to albumin ratio (CAR) may be associated with prognosis of esophageal cancer (EC); however, the results are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of preoperative GNRI and CAR on the prognosis of EC. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to analyze the relationship between GNRI/CAR and prognosis. Publication bias was estimated using Begg's funnel plot asymmetry test and Egger's test. A total of 21 studies comprising 5,018 patients were included in the meta-analysis. A decreased GNRI was significantly associated with poorer overall survival (OS) (HR = 1.808, 95% CI: 1.489-2.196, P < 0.001) and cancer-specific survival (CSS) (HR = 1.769, 95% CI: 1.193-2.624, P = 0.005), and an increased CAR was significantly associated with lower OS (HR = 2.179, 95% CI: 1.587-2.992, P < 0.001), CSS (HR = 1.733, 95% CI: 1.333-2.253, P < 0.001), and recurrence-free survival (HR = 2.178, 95% CI: 1.328-3.573, P = 0.002). Thus, preoperative GNRI and CAR may be noninvasive and powerful tools for predicting survival outcomes in patients with EC.

Low Expression of Keratin17 is Related to Poor Prognosis in Bladder Cancer.

OBJECTIVE: To investigate the association between KRT17 and the prognosis in bladder cancer patients. METHODS: The clinical data of 101 patients with bladder cancer from May 2013 to May 2015 were retrospectively analyzed. At the same time, the expression of KRT17 and its correlation with clinicopathological factors were examined by immunohistochemistry. We search the prognostic value of KRT17 in bladder cancer from the cancer genome map (TCGA) online database. To explore the possible cellular mechanism, gene set enrichment analysis (GSEA) was used. The patients were divided into two groups: high expression of KRT17 and low expression of KRT17. The patients were followed up for 5 years to observe the survival. Kaplan-Meier method and Log rank test were used for univariate survival analysis, and Cox regression analysis was used for multivariate analysis. Finally, a nomogram was constructed on this basis for internal verification. RESULTS: Among the 101 patients, 46 (45.5%) were in the KRT17 low expression group and 55 (54.5%) in the high KRT17 expression group. After 5 years of follow-up, 79 patients survived with a survival rate of 78.2% and 22 patients died with a mortality rate of 21.8%. Kaplan-Meier survival analysis showed that OS and PFS of patients with high expression of KRT17 were significantly higher than those of patients with low expression of KRT17 (p<0.001, p=0.005). Cox multivariate analysis showed that KRT17 expression was an independent risk factor for tumor progression (p=0.019). And tumor size, vascular tumor thrombus, and T stage also affected tumor progression (p<0.05). In the internal validation, the c-index of nomogram was 0.898 (95% CI: 0.854-0.941). CONCLUSION: The decreased expression of KRT17 is associated with poor prognosis in patients with bladder cancer. KRT17 can be used as a novel predictive biomarker to provide a new therapeutic target for bladder cancer patients.