Expression, Prognostic Value, and Immune Infiltration of MTHFD Family in Bladder Cancer.

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.

Incidence, Prognostic Factors, and Survival of Patients with Renal Cancer: A Population-Based Study.

BACKGROUND: The main objective of this article is to understand trends in the incidence of renal cancer and to construct a nomogram to predict the prognosis of patients with renal cancer by analyzing clinical parameters. METHODS: We extracted data from the Surveillance, Epidemiology and End Results (SEER) database for patients with renal cancer from 2010 to 2015. The incidence rate was calculated to understand the trend of renal cancer in recent years, and the Kaplan-Meier method was used to analyze the relationship between patients' clinical variables and overall survival. Nomogram and calibration curves were constructed based on factors predicted by multivariate Cox regression. RESULTS: Data from 68,496 eligible renal cancer patients were included in the study. The incidence of renal cancer was higher in men than women and tended to stabilize over time. We further found that age, gender, marital status, AJCC stage, histological type, metastatic disease, and surgery were independent parameters for prognosis in renal cancer patients. Finally, a nomogram was constructed based on the above parameters, and its validity was verified with the agreement index and calibration curve. CONCLUSION: Renal cancer incidence trend gradually stabilized. Seven independent parameters for renal cancer patients were obtained by analysis and utilized to construct a nomogram that could provide guidance for clinical practice.

Incidence, prognostic factors and survival in bladder cancer patients: a population-based study.

Background: The aim of this study was to investigate the incidence, epidemiologic characteristics, prognostic factors and survival of patients with bladder cancer. Methods: Bladder cancer patients diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the independent prognostic factors for overall survival. Kaplan-Meier survival analysis and nomogram analysis were constructed based on the identified independent prognostic factors. Results: A total of 95,329 eligible bladder cancer patients were included in this study. Eight independent risk factors, including age, histologic type, race, tumor, node and metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, surgery, tumor metastasis and summary stage, were recognized by using multivariate logistic regression models. By comprising these factors, a predictive nomogram was constructed to predict the 1-, 3-, and 5-year overall survival possibilities. The concordance index and calibration curve showed that the nomogram had robust and accurate performance. Conclusions: Bladder cancer is the most common cancer of the urinary system, but the overall incidence has been decreasing yearly since 1992. Our results demonstrate eight factors significantly associated with overall survival in bladder cancer patients. Based on these factors, we established and validated a nomogram, which has the potential to provide an individualized prediction of overall survival in patients with bladder cancer.

Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth.

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer prophylaxis and treatment is unclear. In this study, we constructed a recombinant plasmid encoding Flk-1 and C3d3 fusion proteins and investigated its transient expression in vitro in transfected eukaryotic cells and its antibody response in immunized mice. Subsequently, we investigated the vaccine's ability to elicit an immune response leading to suppression of angiogenesis and tumor growth in mice bearing bladder transitional cell carcinoma. Using Western blotting, immunocytochemistry, and flow cytometry, we detected the expression of Flk-1 and C3d3 fusion proteins in COS-7 cells transfected with these recombinant plasmids. Further binding experiment using CR2 (C3d receptor) positive Raji cells that were incubated with transfected COS-7 supernatant indicated that C3d was successfully fused to Flk-1. Although both vaccines elicited peak antibody levels at 5 weeks, Flk-1-specific antibody titer in pSG.SS.Flk-1(ECD).C3d3.YL-immunized mice was significantly higher when compared to pSG.SS.Flk-1(ECD).YL-immunized mice. The results of experiments with bladder tumor-bearing mice showed that the vaccine inhibited tumor growth significantly. These results suggest that C3d plays a critical role in tumor immunotherapy by promoting antibody response in Flk-1-based DNA vaccines. This approach may provide a new strategy for the rational design of anti-angiogenic therapies for the treatment of solid tumors and provide a basis for the further exploitation and application of the anti-angiogenesis DNA vaccines.