Immunotherapeutic Value of MAP1LC3C and Its Candidate FDA-Approved Drugs Identified by Pan-Cancer Analysis, Virtual Screening and Sensitivity Analysis

Xudong Zhang; Kunhang Li; Shiyu Zhong; Shengyu Liu; Tao Liu; Lishuai Li; Shuo Han; Qingqing Zhai; Nan Bao; Xin Shi; Yijun Bao

doi:10.3389/fphar.2022.863856

Immunotherapeutic Value of MAP1LC3C and Its Candidate FDA-Approved Drugs Identified by Pan-Cancer Analysis, Virtual Screening and Sensitivity Analysis

Front Pharmacol. 2022 Mar 2:13:863856. doi: 10.3389/fphar.2022.863856. eCollection 2022.

Authors

Xudong Zhang¹, Kunhang Li¹, Shiyu Zhong¹, Shengyu Liu¹, Tao Liu¹, Lishuai Li¹, Shuo Han¹, Qingqing Zhai², Nan Bao³, Xin Shi^{4

5}, Yijun Bao¹

Affiliations

¹ Department of Neurosurgery, The Fourth Hospital of China Medical University, Shenyang, China.
² School of Management, Shanghai University, Shanghai, China.
³ College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.
⁴ School of Maths and Information Science, Shangdong Technology and Business University, Yantai, China.
⁵ Business School, All Saints Campus, Manchester Metropolitan University, Manchester, United Kingdom.

Abstract

Background: The autophagy pathway within the tumour microenvironment can be regulated to inhibit or promote tumour development. In the fight against tumour growth, immunotherapy induces an anti-tumour immune response, whereas autophagy modulates this immune response. A key protein in the autophagy pathway, microtubule-associated protein 1 light chain 3 (MAP1LC3), has recently become a hotspot for tumour research. As a relatively novel member, the function of MAP1LC3C in tumours still need to be investigated. Therefore, the goal of this study was to look into the possible link between MAP1LC3C and immunotherapy for 33 kinds of human malignancies by using pan-cancer analysis. Methods: High-throughput sequencing data from The Cancer Genome Atlas, Genotype-Tissue Expression Project and Cancer Cell Line Encyclopedia databases, combined with clinical data, were used to analyze the expression of MAP1LC3C in 33 types of cancer, as well as patient prognosis and neoplasm staging. Activity scores were calculated using ssGSEA to assess the MAP1LC3C activity in pan-cancer. Associations between MAP1LC3C and the tumour microenvironment, including immune cell infiltration and immunomodulators, were analyzed. Moreover, tumour tissue ImmuneScores and StromalScores were analyzed using the ESTIMATE algorithm. Additionally, associations between MAP1LC3C and tumour mutational burden/microsatellite instability, were investigated. Finally, based on the expression and structure of MAP1LC3C, the United States Food and Drug Administration (FDA)-approved drugs, were screened by virtual screening, molecular docking and NCI-60 drug sensitivity analysis. Results: Our study found that MAP1LC3C was differentially expressed in tumour and normal tissues in 23 of 33 human cancer types, among which MAP1LC3C had prognostic effects in 12 cancer types, and MAP1LC3C expression was significantly correlated with tumour stage in four cancer types. In addition, MAP1LC3C activity in 14 cancer types was consistent with changes in transcription levels. Moreover, MAP1LC3C strongly correlated with immune infiltration, immune modulators and immune markers. Finally, a number of FDA-approved drugs were identified via virtual screening and drug sensitivity analysis. Conclusion: Our study investigated the prognostic and immunotherapeutic value of MAP1LC3C in 33 types of cancer, and several FDA-approved drugs were identified to be highly related to MAP1LC3C and can be potential cancer therapeutic candidates.

Keywords: immunotherapy; molecualr docking; pan-cancer analysis; prognosis; tumor microenvironment.