Zhang Xudong, Li Kunhang, Zhong Shiyu, Liu Shengyu, Liu Tao, Li Lishuai, Han Shuo, Zhai Qingqing, Bao Nan, Shi Xin, Bao Yijun
Department of Neurosurgery, The Fourth Hospital of China Medical University, Shenyang, China.
School of Management, Shanghai University, Shanghai, China.
Front Pharmacol. 2022 Mar 2;13:863856. doi: 10.3389/fphar.2022.863856. eCollection 2022.
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. 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. 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. 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.
肿瘤微环境中的自噬途径可被调节以抑制或促进肿瘤发展。在对抗肿瘤生长的过程中，免疫疗法诱导抗肿瘤免疫反应，而自噬调节这种免疫反应。自噬途径中的关键蛋白微管相关蛋白1轻链3（MAP1LC3）最近成为肿瘤研究的热点。作为一个相对较新的成员，MAP1LC3C在肿瘤中的功能仍有待研究。因此，本研究的目的是通过泛癌分析来探究MAP1LC3C与33种人类恶性肿瘤免疫疗法之间的可能联系。利用来自癌症基因组图谱、基因型-组织表达项目和癌细胞系百科全书数据库的高通量测序数据，并结合临床数据，分析MAP1LC3C在33种癌症类型中的表达情况，以及患者的预后和肿瘤分期。使用单样本基因集富集分析（ssGSEA）计算活性评分，以评估泛癌中MAP1LC3C的活性。分析MAP1LC3C与肿瘤微环境之间的关联，包括免疫细胞浸润和免疫调节剂。此外，使用ESTIMATE算法分析肿瘤组织的免疫评分和基质评分。此外，还研究了MAP1LC3C与肿瘤突变负荷/微卫星不稳定性之间的关联。最后，基于MAP1LC3C的表达和结构，通过虚拟筛选、分子对接和NCI-60药物敏感性分析，筛选出美国食品药品监督管理局（FDA）批准的药物。我们的研究发现，在33种人类癌症类型中的23种中，MAP1LC3C在肿瘤组织和正常组织中存在差异表达，其中MAP1LC3C在12种癌症类型中具有预后作用，并且在4种癌症类型中，MAP1LC3C的表达与肿瘤分期显著相关。此外，14种癌症类型中MAP1LC3C的活性与转录水平的变化一致。此外，MAP1LC3C与免疫浸润、免疫调节剂和免疫标志物密切相关。最后，通过虚拟筛选和药物敏感性分析确定了一些FDA批准的药物。我们的研究调查了MAP1LC3C在33种癌症类型中的预后和免疫治疗价值，并确定了几种与MAP1LC3C高度相关且可能成为癌症治疗候选药物的FDA批准药物。
