The association between the triglyceride-glucose index and prognosis in postoperative renal cell carcinoma patients: a retrospective cohort study.

Background: Insulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride-glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients. Methods: A total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride-glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes. Results: The TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan-Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors. Conclusion: The TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets.

Identification of tryptophan metabolism- and immune-related genes signature and prediction of immune infiltration landscape in bladder urothelial carcinoma.

Introduction: Tryptophan metabolism is indirectly involved in immune tolerance and promotes response to anticancer drugs. However, the mechanisms underlying tryptophan metabolism and immune landscape in bladder urothelial carcinoma (BLCA) are not fully understood. Methods: A BLCA dataset containing 406 tumor samples with clinical survival information and 19 normal samples were obtained from the Cancer Genome Atlas database. The validation set, GSE32894, contained 223 BLCA tumor samples with survival information, and the single-cell dataset, GSE135337, included seven BLCA tumor samples; both were obtained from the gene expression omnibus database. Univariate and multivariate Cox regression analyses were conducted to evaluate clinical parameters and risk scores. Immune infiltration and checkpoint analyses were performed to explore the immune landscape of BLCA. Single-cell analysis was conducted to further identify the roles of model genes in BLCA. Finally, NAMPT expression in BLCA and adjacent tissues was detected using RT-qPCR, CCK-8 and Transwell assays were conducted to determine the role of NAMPT in BLCA cells. Results: Six crossover genes (TDO2, ACAT1, IDO1, KMO, KYNU, and NAMPT) were identified by overlap analysis of tryptophan metabolism-related genes, immune-related genes, and differentially expressed genes (DEGs). Three biomarkers, NAMPT, IDO1, and ACAT1, were identified using Cox regression analysis. Accordingly, a tryptophan metabolism- and immune-related gene risk model was constructed, and the patients were divided into high- and low-risk groups. There were significant differences in the clinical parameters, prognosis, immune infiltration, and immunotherapy response between the risk groups. RT-qPCR revealed that NAMPT was upregulated in BLCA samples. Knocking down NAMPT significantly inhibited BLCA cell proliferation, migration, and invasion. Discussion: In our study, we constructed a tryptophan metabolism- and immune-related gene risk model based on three biomarkers, namely NAMPT, IDO1, and ACAT1, that were significantly associated with the progression and immune landscape of BLCA. The risk model could effectively predict patient prognosis and immunotherapy response and can guide individualized immunotherapy.

Identifying prognostic characteristics of m6A-related glycolysis gene and predicting the immune infiltration landscape in bladder cancer.

BACKGROUNDS: Glucose metabolism is associated with the development of cancers, and m6A RNA methylation regulator-related genes play vital roles in bladder urothelial carcinoma (BLCA). However, the role of m6A-related glucose metabolism genes in BLCA occurrence and development has not yet been reported. Our study aims to integrate m6A- and glycolysis-related genes and find potential gene targets for clinical diagnosis and prognosis of BLCA patients. METHODS: Sequencing data and clinical information on BLCA were extracted from common databases. Univariate Cox analysis was used to screen prognosis-related m6A glucose metabolism genes; BLCA subtypes were distinguished using consensus clustering analysis. Subsequently, genes associated with BLCA occurrence and development were identified using the "limma" R package. The risk score was then calculated, and a nomogram was constructed to predict survival rate of BLCA patients. Functional and immune microenvironment analyses were performed to explore potential functions and mechanisms of the different risk groups. RESULTS: Based on 70 prognosis-related m6A glucose metabolism genes, BLCA was classified into two subtypes, and 34 genes associated with its occurrence and development were identified. Enrichment analysis revealed an association of genes in high-risk groups with tricarboxylic acid cycle function and glycolysis. Moreover, significantly higher levels of seven immune checkpoints, 14 immune checkpoint inhibitors, and 32 immune factors were found in high-risk score groups. CONCLUSIONS: This study identified two biomarkers associated with BLCA prognosis; these findings may deepen our understanding of the role of m6A-related glucose metabolism genes in BLCA development. We constructed a m6A-related glucose metabolism- and immune-related gene risk model, which could effectively predict patient prognosis and immunotherapy response and guide individualized immunotherapy.

FTO promotes proliferation and migration of bladder cancer via enhancing stability of STAT3 mRNA in an m6A-dependent manner.

N6-Methyladenosine (m6A) plays a key role in the occurrence and development of various cancers. Fat mass and obesity-associated protein (FTO) was is involved in multiple cancers owing to its demethylase activity, and the molecular mechanism underlying FTO-promoted bladder cancer proliferation and migration via the regulation of RNA stability requires further investigation. In the present study, FTO was upregulated in bladder cancer and related to poor prognosis. Gain- and loss-of-function experiments showed that the upregulation of FTO promoted bladder cancer proliferation and migration. Mechanistic studies showed that FTO enhanced the stability of signal transducer and activator of transcription 3 (STAT3) mRNA in an m6A-dependent manner, thereby increasing STAT3 expression, which subsequently promoted P-STAT3 expression and activated STAT3 signalling pathway. Overall, this study revealed that the critical role of FTO in the progression of bladder cancer and could provide a novel avenue to regulate oncogene STAT3.

[Effect of aspirin administration for the treatment of osteoporosis in ovariectomized rat model].

OBJECTIVE: To explore the therapeutic effects of aspirin on postmenopausal osteoporosis and understand its action mechanism. METHODS: Forty three-month-old female SD rats were randomly divided into 5 groups (n = 8 each): sham group, OVX group and aspirin groups (A1, A2 & A3). The OVX and aspirin groups were ovariectomized (OVX). All rats underwent BMD (bone mineral density) scan at the time of OVX and 3 months after OVX. After the animal model of osteoporosis was established, aspirin groups were intragastrically administered at a dose of 8.93 mg×kg(-1)×d(-1) (A1), 26.79 mg×kg(-1)×d(-1) (A2) and 80.36 mg×kg(-1)×d(-1) (A3) daily in OVX rats. Three months later, the BMD and micro-architecture of vertebrae were measured by dual-energy X-ray absorptiometry and microtomography. Alkaline phosphatase and osteocalcin were measured in peripheral blood. The trabecular architecture changes were observed by histomorphology. Axial compression tests were used to evaluate the mechanical properties of vertebral specimens and three-point bending tests used for femur shaft. RESULTS: Three months after ovariectomy, BMD was significantly lower than preoperative. BMD in aspirin treated groups was significantly higher than that in OVX group. Alkaline phosphatase in peripheral blood decreased significantly in aspirin groups than those in OVX, but osteocalcin had no significant difference between aspirin and OVX groups. The microtomography reconstruction analysis also showed that the trabecular thickness, trabecular number and BMD increased significantly in aspirin groups than those in OVX. And there was no significant difference between A3 and sham groups. The results of biomechanical test showed that the maximum compression load of lumbar spine and three-point bending load of femur shaft were significantly higher in aspirin groups than those in OVX group. CONCLUSION: Aspirin can promote trabecular bone remodeling, improve three-dimensional structure of trabecular bone and increase bone density of cancellous in osteoporotic rats by stimulating bone formation. It may become a new drug for the treatment of osteoporosis.