Research Paper|Volume 13, Issue 8|pp 11381—11410

Seven interferon gamma response genes serve as a prognostic risk signature that correlates with immune infiltration in lung adenocarcinoma

Boyang Yao^1,², Lixin Wang⁴, Heyong Wang^2,³, Jinxia Bao^2,³, Qiwen Li^2,³, Fengzhi Yu⁴, Wenjing Zhu^1,², Li Zhang³, Wang Li⁵, Zhan Gu⁴, Ke Fei², Peng Zhang², Fan Zhang^2,³, Xiaoying Huang¹

¹Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou 325000, Zhejiang, China
²Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Life Science and Technology, Shanghai 200433, China
³Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China
⁴Department of Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China
⁵College of Biological and Environmental Engineering, Binzhou University, Binzhou 256600, Shandong, China

* Equal contribution

Received: September 21, 2020Accepted: January 4, 2021Published: April 4, 2021

https://doi.org/10.18632/aging.202831

Copyright: © 2021 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Interferon-gamma (IFN-γ) plays a complex role in modulating tumor microenvironment during lung adenocarcinoma (LUAD) development. In order to define the role of IFN-γ response genes in LUAD progression, we characterized the gene expression, mutation profile, protein-protein interaction of 24 IFN-γ response genes, which exhibited significant hazard ratio in overall survival. Two subgroups of LUAD from the TCGA cohort, which showed significant difference in the survival rate, were identified based on the expression of these genes. Furthermore, LASSO penalized cox regression model was used to derive a risk signature comprising seven IFN-γ response genes, including CD74, CSF2RB, PTPN6, MT2A, NMI, LATS2, and PFKP, which can serve as an independent prognostic predictor of LUAD. The risk signature was validated in an independent LUAD cohort. The high risk group is enriched with genes regulating cell cycle and DNA replication, as well as a high level of pro-tumor immune cells. In addition, the risk score is negatively correlated with the expression of immune metagenes, but positively correlated with DNA damage repair genes. Our findings reveal that seven-gene risk signature can be a valuable prognostic predictor for LUAD, and they are crucial participants in tumor microenvironment of LUAD.