Luo Jieyan, Hu Qipeng, Gou Maling, Liu Xiaoke, Qin Yi, Zhu Jiao, Cai Chengzhi, Tian Tian, Tu Zegui, Du Yijia, Deng Hongxin
Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2021 Oct 1;11:680402. doi: 10.3389/fonc.2021.680402. eCollection 2021.
Microtubule-associated proteins (MAPs) have been considered to play significant roles in the tumor evolution of non-small cell lung cancer (NSCLC). Nevertheless, mRNA transcription levels and prognostic value of distinct MAPs in patients with NSCLC remain to be clarified.
In this study, the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA) database, and Human Protein Atlas were utilized to analyze the relationship between mRNA/protein expression of different MAPs and clinical characteristics in NSCLC patients, including tumor type and pathological stage. The correlation between the transcription level of MAPs and overall survival (OS) of NSCLC patients was analyzed by Kaplan-Meier plotter. Besides, 50 frequently altered neighbor genes of the MAPs were screened out, and a network has been constructed the cBioPortal and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) dataset. Meanwhile, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the expression data of MAPs and their 50 frequently altered neighbor genes in NSCLC tissues. Furthermore, The Cancer Immunome Atlas (TCIA) was utilized to analyze the relationship between MAP expression and the response to immunotherapy. Finally, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to verify the expression of MAPs in 20 patients with NSCLC.
The present study discovered that the mRNA transcription levels of MAP7/7D2 were enriched in NSCLC tissues, while those of the MAP2/4/6/7D3 were lower in NSCLC specimens than those in control specimens. The mRNA transcription level of MAP6 was significantly associated with the advanced stage of NSCLC. Besides, survival analysis indicated that higher mRNA expressions of MAP2/4/6/7/7D3 were correlated considerably with favorable OS of NSCLC patients, whereas increased mRNA expression levels of MAP1A/1S were associated with poor OS. Moreover, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was significantly correlated with immunophenoscore (IPS) in NSCLC patients.
Our analysis indicated that MAP1A/1S could serve as potential personalized therapeutic targets for patients with NSCLC, and the enriched MAP2/4/6/7/7D3 expression could serve as a biomarker for favorable prognosis in NSCLC. Besides, the expression of MAP1A/1B/1S/4/6/7D1/7D3 was closely related to the response to immunotherapy. Taken together, MAP expression has potential application value in the clinical treatment and prognosis assessment of NSCLC patients, and further verifiable experiments can be conducted to verify our results.
微管相关蛋白（MAPs）被认为在非小细胞肺癌（NSCLC）的肿瘤进展中起重要作用。然而，NSCLC患者中不同MAPs的mRNA转录水平和预后价值仍有待阐明。
在本研究中，利用Oncomine数据库、基因表达谱交互式分析（GEPIA）数据库和人类蛋白质图谱分析不同MAPs的mRNA/蛋白质表达与NSCLC患者临床特征（包括肿瘤类型和病理分期）之间的关系。通过Kaplan-Meier绘图仪分析MAPs转录水平与NSCLC患者总生存期（OS）之间的相关性。此外，筛选出MAPs的50个经常改变的邻近基因，并利用cBioPortal和基因/蛋白质相互作用检索搜索工具（STRING）数据集构建一个网络。同时，我们对NSCLC组织中MAPs及其50个经常改变的邻近基因的表达数据进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。此外，利用癌症免疫组图谱（TCIA）分析MAP表达与免疫治疗反应之间的关系。最后，我们使用逆转录定量聚合酶链反应（RT-qPCR）验证20例NSCLC患者中MAPs的表达。
本研究发现，MAP7/7D2的mRNA转录水平在NSCLC组织中富集，而MAP2/4/6/7D3在NSCLC标本中的mRNA转录水平低于对照标本。MAP6的mRNA转录水平与NSCLC的晚期显著相关。此外，生存分析表明，MAP2/4/6/7/7D3较高的mRNA表达与NSCLC患者良好的OS显著相关，而MAP1A/1S的mRNA表达水平升高与不良OS相关。此外，MAP1A/1B/1S/4/6/7D1/7D3的表达与NSCLC患者的免疫表型评分（IPS）显著相关。
我们的分析表明，MAP1A/1S可作为NSCLC患者潜在的个性化治疗靶点，而富集的MAP2/4/6/7/7D3表达可作为NSCLC良好预后的生物标志物。此外，MAP1A/1B/1S/4/6/7D1/7D3的表达与免疫治疗反应密切相关。综上所述，MAP表达在NSCLC患者的临床治疗和预后评估中具有潜在的应用价值，可进行进一步的验证实验来验证我们的结果。
