Autophagy-related genes prognosis signature as potential predictive markers for immunotherapy in hepatocellular carcinoma

Deli Mao; Zhe Zhang; Xin Zhao; Xiaoqiang Dong

doi:10.7717/peerj.8383

Autophagy-related genes prognosis signature as potential predictive markers for immunotherapy in hepatocellular carcinoma

PeerJ. 2020 Jan 17:8:e8383. doi: 10.7717/peerj.8383. eCollection 2020.

Authors

Deli Mao^#¹, Zhe Zhang^#¹, Xin Zhao¹, Xiaoqiang Dong¹

Affiliation

¹ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

^# Contributed equally.

Abstract

Autophagy-related genes (ATGs) depress tumorigenesis. However, in tumor tissue, it promotes tumor progression. Here, we demonstrated that 63 ATGs were differentially expressed in normal tissues and tumor tissues of hepatocellular carcinoma (HCC), and seven prognostic-related genes were chosen to establish prognostic risk signatures. It is not just an independent prognostic factor for HCC, but also closely related to the degree of malignancy of HCC. Further, the hallmarks of PI3K-AKT-mTOR signaling was significantly enriched in the high-risk group. Moreover, AKT-pS473 and mTOR-pS2448 expression was down-regulated and correlated with patient prognosis in high-risk group. Finally, we demonstrate that the prognosis signature of ATGs is closely related to immune cell infiltration and PD-L1 expression. In conclusion, ATGs are a crucial factor in the malignant progression of HCC and will be a new prognostic marker for diagnosis and treatment. ATGs prognostic signatures are potentially useful for predicting PD-L1 therapeutic effects.

Keywords: Autophagy-related genes; Hepatocellular carcinoma; Immunotherapy; Prognosis; Signature.

Grants and funding

This study was supported by grants from the National Science Foundation of China (NSFC, No. 31770985), the Social Development Project of Jiangsu Province (No. BE2019665), the Postdoctoral Science Foundation Grant of China (No. 2016M591913), the Jiangsu Provincial Medical Youth Talent (No. QNRC2016732), the Jiangsu Provincial “Six Peaks Talent” Program (No. 2016-WSW-043), the Suzhou Municipal Project of Gusu Health Talent, Young Top Talent (No. 2018-057), the Gusu Health Talents Cultivation Program (No. GSWS2019028), the Scientific Research Program of Jiangsu Provincial “333 Projects” (No. BRA2019327), the Science and Technology Program of Suzhou City, China (Nos. SYS2019053 and SLC201906), the Provincial Natural Science Foundation of Jiangsu Province (No. BK20161225), and the Scientific Research Program of Jiangsu Provincial Commission of Health and Family Planning (No. H201620). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.