Prognostic value and immune infiltration analysis of activating transcription factor 5 in clear cell renal cell carci-noma

ZHI Xi; HE Ye

doi:10.13820/j.cnki.gdyx.20243012

Abstract：Objective To investigate the expression level of activating transcription factor 5(ATF5)in clear cell renal cell carcinoma(ccRCC),explore its correlation with immune infiltration,and evaluate its prognostic value.Meth-ods ATF5 mRNA expression data were obtained from The Cancer Genome Atlas kidney renal clear cell carcinoma(TC-GA-KIRC)cohort and analyzed using R software.The expression differences between tumor and adjacent normal tissues were evaluated.Kruskal-Wallis and logistic regression analyses were applied to assess the association between ATF5 ex-pression and clinicopathological characteristics.Kaplan-Meier survival curves,time-dependent receiver operating char-acteristic(ROC)curves,and Cox regression analyses were used to evaluate the prognostic significance of ATF5.Gene set enrichment analysis(GSEA)was employed to predict ATF5-related biological pathways.Gene mutation data were ob-tained from the cBioPortal database.Single-sample gene set enrichment analysis(ssGSEA)was used to explore the cor-relation between ATF5 expression and immune cell infiltration.Results ATF5 expression was significantly upregulated in ccRCC tissues compared to normal tissues(P＜0.001)and demonstrated good discriminatory power(AUC=0.800).Higher ATF5 expression was significantly associated with advanced TNM stage and histological grade(P＜0.05).Kaplan-Meier analysis indicated that patients with high ATF5 expression had poorer overall survival(OS),progression-free survival(PFS),and disease-specific survival(DSS)(P＜0.01).Time-dependent ROC curves confirmed the prog-nostic potential of ATF5.Univariate Cox analysis showed that ATF5 was significantly correlated with OS,while multivari-ate analysis identified age,pathological stage,and histological grade as independent prognostic factors(P＜0.05).GSEA suggested that ATF5 was mainly involved in pathways such as the cell cycle.Mutation analysis showed distinct genetic al-terations between high and low ATF5 expression groups.ssGSEA revealed that ATF5 expression was positively correlated with regulatory T cells(Tregs),Th1,and Th2 cell infiltration,with the strongest correlation observed with Tregs(R=0.352,P＜0.001).Conclusion ATF5 is highly expressed in ccRCC and may serve as a prognostic biomarker and po-tential immune-related therapeutic target.