Expression of Microtubule-Associated Proteins in Relation to Prognosis and Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Jieyan Luo; Qipeng Hu; Maling Gou; Xiaoke Liu; Yi Qin; Jiao Zhu; Chengzhi Cai; Tian Tian; Zegui Tu; Yijia Du; Hongxin Deng

doi:10.3389/fonc.2021.680402

Expression of Microtubule-Associated Proteins in Relation to Prognosis and Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Front Oncol. 2021 Oct 1:11:680402. doi: 10.3389/fonc.2021.680402. eCollection 2021.

Authors

Jieyan Luo¹, Qipeng Hu¹, Maling Gou², Xiaoke Liu¹, Yi Qin¹, Jiao Zhu¹, Chengzhi Cai¹, Tian Tian¹, Zegui Tu¹, Yijia Du¹, Hongxin Deng³

Affiliations

¹ Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
² State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
³ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

Abstract

Background: 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.

Methods: 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 via 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.

Results: 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.

Conclusions: 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.

Keywords: MAP; The Cancer Genome Atlas (TCGA); immunotherapy; non-small cell lung cancer; prognosis.