Clear cell renal cell carcinoma (ccRCC) is the most invasive type with high metastasis risk and high recurrence rate in renal cell carcinoma and there is a pressing need to explore novel prognostic predictors and therapeutic targets for ccRCC. Activating transcription factor 3 (ATF3), an oncogene or a suppressor for tumor, has been poorly reported in ccRCC. Here, we comprehensively clarified the prognostic value and potential function of ATF3 in ccRCC. By analyzing ATF3 in ccRCC several TCGA-based online databases, we found that ATF3 expression is decreased in ccRCC and indicate that ATF3 is significantly associated with the prognosis of ccRCC patients. hsa-miR-221-3p might be the most potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of upstream lncRNAs showed PAXIP1-AS2 and OIP5-AS1 might be the most potential upstream lncRNAs of hsa-miR-221-3p/ATF3 axis in ccRCC. GO and KEGG results implied that ATF3 is involved in the regulation of apoptotic signaling pathway in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis showed a positive correlation between ATF3 and ER stress. According to present study, down-regulated ATF3 promotes renal clear cell carcinoma progression through PAXIP1-AS2 and OIP5-AS1/ hsa-miR-221-3p/ATF3 axis regulation of endoplasmic reticulum stress.
Background and Objective: Lung adenocarcinoma is the most common and aggressive subtype of lung cancer, with the poor overall prognosis. IL2 is one of the earliest cytokines discovered that stimulates lymphocyte proliferation. However, the role of IL2 in LUAD has not been clarified.
Methods: UALCAN, The HPA and TIMER database were used to investigate IL2 expression in LUAD. HPA, PrognoScan Database Analysis and Kaplan-Meier plotter database were used to explore the survival curve evaluating the prognostic value of IL2 for LUAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of IL2-interacting genes identified by GeneMANIA database. TIMER was used to analyze the correlation of IL2 and immune cell infiltration or immune checkpoint expression level in LUAD.
Results: In present study, the results showed that the expression of IL-2 in lung adenocarcinoma was lower than that in the normal control group by means of bioinformatics analysis of the TIMER, UALCAN and HPA public databases. Moreover, LUAD patients with downregulated IL2 expression exhibited poor overall survival. Besides, IL2 was significantly positively correlated with various immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in LUAD. And IL2 was also markedly positively associated with biomarkers of these infiltrated immune cells. IL2 expression was also positively correlated with PD-1, PD-L1 and CTLA-4 expression.
Conclusion: In summary, our results indicate that down-regulation of interleukin-2 predicts poor prognosis and associated with immune escape in LUAD and IL2 could serve as a potential novel prognostic biomarker for LUAD.
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