Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy

Zi-Jian Zhang; Kun-Peng Wang; Yun-Peng Huang; Chong Jin; Hao Jiang; Li Xiong; Zhao-Yi Chen; Yu Wen; Zhong-Tao Liu; Jing-Gang Mo

doi:10.3389/fphar.2022.857774

Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy

Front Pharmacol. 2022 May 3:13:857774. doi: 10.3389/fphar.2022.857774. eCollection 2022.

Authors

Affiliations

¹ Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
² Department of General Surgery, Taizhou Central Hospital (Taizhou University, Hospital), Taizhou, China.

Abstract

Autophagy related gene 101 (ATG101) plays a significant role in the occurrence and development of tumours by responding to stress. Our research aims to illustrate the correlation between the expression of ATG101 and tumor prognosis and its potential role and mechanism in tumor immunity and photodynamic therapy (PDT). First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, Kaplan-Meier curves was applied in cholangiocarcinoma (CHOL) and liver hepatocellular carcinoma (LIHC) datasets for survival analysis. Next, the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints was analysed. Besides, the relationship between the expression of ATG101 and methyltransferase. GSEA was used to study the function and the related transcript factors of ATG101 in CHOL and LIHC. The effect of PDT on ATG101 was verified by microarray, qPCR and western blot. Then the effect of ATG101 and its regulatory factors on apoptosis were verified by siRNA, lentivirus transfection and Chip-qPCR. Comprehensive analysis showed that ATG101 was overexpressed in different tumours. Kaplan-Meier curves found that ATG101 was associated with poor prognosis in tumours (including CHOL and LIHC). We found that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in CHOL and LIHC. Subsequent validation tests confirmed that the up-regulated ATG101 after PDT treatment is not conducive to the occurrence of apoptosis of cholangiocarcinoma cells. The high expression of ATG101 may be induced by the early stress gene EGR2. Our study highlights the significance of ATG101 in the study of tumour immunity and photodynamic therapy from a pan-cancer perspective.

Keywords: apoptosis; autophagy-related gene 101; cholangiocarcinoma; immune checkpoint gene; pan-cancer; photodynamic therapy.