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.
Highlights
Autophagy is a process that occurs in all eukaryotes, involving in the capture by an autophagosome and transport to the lysosomes for decomposition and recycling (Ohsumi, 2012; Morishita and Mizushima, 2019)
The gene expression profiles of various tumour cell lines downloaded from the CCLE database, and the MAP1LC3C expression levels of 21 tissues according to their tissue sources were analyzed
MAP1LC3C expression was significantly correlated with the neoplasm staging of a few cancers, including HNSC, KICH, KIRC and THCA (Figure 2)
Summary
Autophagy is a process that occurs in all eukaryotes, involving in the capture by an autophagosome and transport to the lysosomes for decomposition and recycling (Ohsumi, 2012; Morishita and Mizushima, 2019). To better cope with stresses in the tumour microenvironment, the autophagy pathways in various cell types can be regulated to inhibit or promote tumour development (Xia et al, 2021). Immunotherapy fights against tumours by arousing the antitumour immune response in the immune system (Zou et al, 2016). Recent studies have shown that autophagy is involved in the various biological processes of immune cells (Clarke and Simon, 2019) and can modulate tumour growth by regulating the immune response (Yang et al, 2018). 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. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
