J Cancer 2022; 13(3):877-889. doi:10.7150/jca.57008 This issue Cite

Research Paper

Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Wenjie Chen1,4*, Wen Li1*, Zhenkun Liu1*, Guangzhi Ma1,2, Yunfu Deng1, Lingling Zhu1, Qinghua Zhou1,3✉

1. Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
2. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
3. Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
4. Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
* These authors have contributed equally to this work

Citation:
Chen W, Li W, Liu Z, Ma G, Deng Y, Zhu L, Zhou Q. Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma. J Cancer 2022; 13(3):877-889. doi:10.7150/jca.57008. https://www.jcancer.org/v13p0877.htm
Other styles

File import instruction

Abstract

Graphic abstract

Background: The tumor microenvironment evidently affects treatment response and clinical outcome. This study aims to construct a tumor microenvironment-based crosstalk between immunotherapy and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in lung adenocarcinoma.

Methods: We used ESTIMATE algorithm to calculate stromal and immune scores. Differentially expressed genes (DEGs) were extracted based on the comprehensive analysis of immune score groups and EGFR-TKI resistance samples. The independent prognostic value of the five selected genes was assessed by univariate/multivariate Cox regression analysis, survival analysis and the receiver operating characteristic (ROC) curve. Correlation analysis was performed using Spearman's rho value through TIMER 2.0.

Results: The Kaplan-Meier survival curve show that patients with higher immune scores have significantly better overall survival. We identified 1328 DEGs from immune score groups and 806 DEGs from the EGFR-TKI resistance cohort GSE123066. A total of 19 co-regulated genes were found, and the Cox regression model produced a significant statistical prognosis for five genes (CENPF, CYSLTR1, GLDN, PIGR and SCGB3A1). Multivariate Cox regression analysis showed that the selected five gene signatures could be used as independent prognostic indicators. Furthermore, GSEA and correlation analysis demonstrated that CENPF was positively correlated to the signalling pathway which related to EGFR-TKI resistance and the well-known bypass gene.

Conclusion: Our findings indicate that CENPF, CYSLTR1, GLDN, PIGR and SCGB3A1 are independent prognostic biomarkers associated with acquired EGFR-TKI resistance and tumor immune cell infiltration in lung adenocarcinoma, and CENPF may be a potential target that can improve immunotherapy efficacy and overcome the acquired EGFR-TKI resistance.

Keywords: lung adenocarcinoma, tumor environment, immune cell infiltration, immunotherapy, EGFR-TKI resistance


Citation styles

APA
Chen, W., Li, W., Liu, Z., Ma, G., Deng, Y., Zhu, L., Zhou, Q. (2022). Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma. Journal of Cancer, 13(3), 877-889. https://doi.org/10.7150/jca.57008.

ACS
Chen, W.; Li, W.; Liu, Z.; Ma, G.; Deng, Y.; Zhu, L.; Zhou, Q. Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma. J. Cancer 2022, 13 (3), 877-889. DOI: 10.7150/jca.57008.

NLM
Chen W, Li W, Liu Z, Ma G, Deng Y, Zhu L, Zhou Q. Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma. J Cancer 2022; 13(3):877-889. doi:10.7150/jca.57008. https://www.jcancer.org/v13p0877.htm

CSE
Chen W, Li W, Liu Z, Ma G, Deng Y, Zhu L, Zhou Q. 2022. Identification of tumor microenvironment‐based genes associated with acquired resistance to EGFR Tyrosine Kinase Inhibitor in Lung Adenocarcinoma. J Cancer. 13(3):877-889.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.