Background: The purpose of this study was to evaluate the risk of cardiovascular mortality (CVM) among patients with bladder cancer (BC). Methods and Materials: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database for patients who were diagnosed with BC by pathology between 2000 and 2016. The standardized mortality rate (SMR) was calculated based on reference data from the general population. Nelson–Aalen cumulative hazard curves were used to assess the risk of experiencing CVM in BC patients. Multivariate competing risk models were performed. Results: In total, data from 237,563 BC patients were obtained from the SEER database for further analysis, of which 21,822 patients experienced CVM; the overall SMR for CVM in BC patients was 1.16 (95% CI: 1.14–1.17). Age, race, sex, year of diagnosis, histologic type, summary stage, surgery, marital status, and college education level were independent predictors of CVM in patients with BC. Conclusions: Patients with BC have a significantly increased risk of experiencing CVM compared to the general population. Pre-identification of high-risk groups and cardiovascular protection interventions are important measures to effectively improve survival in this group of patients.

To systematically evaluate the differences in therapeutic response to chemotherapy or immunotherapy between different molecular subtypes of bladder cancer (BC). A comprehensive literature search was performed up to December 2021. Consensus clusters 1 (CC1), CC2 and CC3 molecular subtypes were used to perform meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the therapeutic response by fix-effect modeling. Eight studies involving 1,463 patients were included. For immunotherapy, CC3 showed the highest response rate (CC1 vs. CC3: OR=0.52, 95% CI=0.34–0.78, p=0.002; CC2 vs. CC3: OR=0.42, 95% CI=0.28-0.62, p<0.001), which was mainly reflected in the highest response rate to atezolizumab (CC1 vs. CC3: OR=0.47, 95% CI=0.29–0.75, p=0.002; CC2 vs. CC3: OR=0.38, 95% CI=0.24–0.59, p<0.001). For chemotherapy, CC3 had the lowest response rate to the overall chemotherapy (CC1 vs. CC3: OR=2.05, 95% CI=1.23–3.41, p=0.006; CC2 vs. CC3: OR=2.48, 95% CI=1.50–4.10, p<0.001). Compared with CC2, CC3 responded poorly to both neo-adjuvant chemotherapy (NAC) (OR=1.93, 95% CI=1.09–3.41, p=0.020) and chemoradiation therapy (CRT) (OR=6.07, 95% CI=1.87–19.71, p<0.001). Compared with CC1, CC3 only showed a poorer response to CRT (OR=4.53, 95% CI=1.26–16.27, p=0.020), and no difference in NAC. Our study suggested that molecular classifications are important predictors of cancer treatment outcomes of BC patients and could identify subgroup patients who are most likely to benefit from specific cancer treatments.

Background Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Recently, immunotherapy has been considered a promising treatment for metastatic ccRCC. NUF2 is a crucial component of the Ndc80 complex. NUF2 can stabilize microtubule attachment and is closely related to cell apoptosis and proliferation. This research is dedicated to investigating the role of NUF2 in ccRCC and the possible mechanisms. Methods First, analysis of NUF2 mRNA expression levels in ccRCC and normal tissues by The Cancer Genome Atlas (TCGA) database and further verified by analysis of independent multiple microarray data sets in the Gene Expression Omnibus (GEO) database. Moreover, we evaluated and identified correlations between NUF2 expression, clinicopathologic variable, and overall survival (OS) in ccRCC by various methods. We investigated the relationship between NUF2 and tumor immune infiltration and the expression of corresponding immune cell markers via the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. Then, we performed functional enrichment analysis of NUF2 co-expressed genes using R software and protein-protein interactions (PPIs) using the search tool used to retrieve interacting genes/proteins (STRING) databases. Results We discovered that NUF2 mRNA expression was upregulated in ccRCC tissues and was associated with sex, grade, pathological stage, lymph node metastasis, and worse prognosis. In addition, NUF2 was positively linked to tumor immune cells in ccRCC. Moreover, NUF2 was closely related to genetic markers of different immune cells. Finally, functional enrichment and protein–protein interaction (PPI) analysis suggested that NUF2 and its closely related genes may be involved in the regulation of the cell cycle and mitosis. Our results suggested that NUF2 is correlated with a poor prognosis and immune infiltration in ccRCC.

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Background: The methylenetetrahydrofolate dehydrogenase (MTHFD) family plays an important role in the development and prognosis of a variety of tumors; however, the role of the MTHFD family in bladder cancer is unclear. Methods: R software, cBioPortal, GeneMANIA, and online sites such as String、LinkedOmics were used for bioinformatics analysis. Results: MTHFD1/1L/2 was significantly upregulated in bladder cancer tissues compared with normal tissues, high expression of the MTHFD family was strongly associated with poorer clinical grading and staging, and bladder cancer patients with upregulated expression of MTHFD1L/2 had a significantly worse prognosis. Gene function and PPI network analysis revealed that the MTHFD family and related genes play synergistic roles in the development of bladder cancer. 800 co-expressed genes related to the MTHFD family were used for functional enrichment analysis, and the results showed that many genes were associated with various oncogenic pathways such as cell cycle and DNA replication. More importantly, the MTHFD family was closely associated with multiple infiltrating immune lymphocytes, including Treg cells, and immune molecules such as TNFSF9, CD274, and PDCD1. Conclusion: Our study shows that MTHFD family genes may be potential prognostic markers and therapeutic targets for patients with bladder cancer.