Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

• Published in: BMC medical genomics 2021-01, Vol.14 (1), p.8-14, Article 8
• Main Authors: Li, Lijuan, Song, Shaohua, Fang, Xiaoling, Cao, Donglin
• Format: Article
• Language: English
• Subjects: Activating transcription factor 3; Activating Transcription Factor 3 - genetics; Activating Transcription Factor 3 - metabolism; ATF3; Biological markers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinogenesis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cytokine receptors; Database mining; Datasets; Female; Functional network analysis; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Hepatocellular carcinoma; Hepatoma; Humans; Infiltration; Kaplan-Meier Estimate; Kinases; Leucine zipper proteins; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Metastases; Mutation; Patients; Prognosis; Prognostic value; Transcription factors
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-020-00852-4

The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. We used UALCAN, ONCOMINE, Kaplan-Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC. ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients. Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.