Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.

BACKGROUND: Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. METHODS: Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. RESULTS: The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. CONCLUSIONS: In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

Comprehensive analysis of the functional and prognostic value of E2F transcription factors in human prostate cancer through data mining and experimental validation.

BACKGROUND: A growing body of evidence shows that E2F transcription factors play a significant role in the tumorigenesis of prostate cancer. However, their functional and prognostic value has not been fully illustrated. Therefore, we used bioinformatics methods to further analyze the possible roles of E2F transcription factors in the development and progression of prostate cancer. METHODS: We explored the expression levels of E2F transcription factors using data from The Cancer Genome Atlas (TCGA) and Oncomine database in paired and unpaired samples. The clinical correlation and prognostic value of E2F transcription factors were assessed. Using the R package "pROC", we judged the diagnostic value of E2F transcription factors. The online website tool cBioPortal was also employed to find possible gene alterations of E2F transcription factors in samples from TCGA. The R package "clusterprofiler" was used to conduct functional analysis. Moreover, we also used the Tumor Immune Estimation Resource to search for the associations between E2F transcription factors and the infiltration levels of 6 kinds of immune cells. Finally, quantitative real-time polymerase chain reaction (PCR) was conducted to validate the expression levels of E2F transcription factors in human paired prostate tissues. RESULTS: E2F1/2/3/5 messenger RNA (mRNA) expression levels were higher in prostate cancer tissues than in normal tissues, while E2F4 and E2F6 mRNA expression levels were lower (P<0.05). All E2F transcription factors were associated with clinical parameters. Kaplan-Meier analysis revealed that E2F1/4/6/8 were notably associated with the overall survival of patients with prostate cancer (P<0.05). Receiver operating characteristic (ROC) curve results showed that except for E2F7, the other E2F transcription factors had diagnostic value for prostate cancer (P<0.05). We further found close associations between E2F transcription factors and the infiltration levels of immune cells. The results of quantitative real-time PCR were consistent with those from public databases. CONCLUSIONS: E2F transcription factor family members are differentially expressed in prostate cancer and are significantly related to the prognosis of patients, suggesting that they may be adopted as biomarkers for prognosis prediction and the treatment of prostate cancer.