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

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.

Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer

“…Moreover, MT2A expression is controversial in lung cancer. A recent study has found that high expression of MT2A is associated with poor prognosis of lung adenocarcinoma [ 23 ]. However, a previous study has found that MT2A expression levels in lung cancer tissues are significantly downregulated compared to paracancerous tissues [ 21 ].…”

The IFN-γ-related long non-coding RNA signature predicts prognosis and indicates immune microenvironment infiltration in uterine corpus endometrial carcinoma

“…Yao et al. constructed the signature of seven IFN-γ-related lncRNAs to assess prognosis in patients with lung adenocarcinoma, in which the high-risk group had a worse prognosis and was associated with high levels of tumor-promoting immune cells ( 51 ). Liu et al.…”

A Naive Bayes model on lung adenocarcinoma projection based on tumor microenvironment and weighted gene co-expression network analysis

“…CD74 (MHC class II invariant chain) is a nonpolymorphic type II transmembrane glycoprotein which not only plays an important role in liver fibrosis and Alzheimer's disease but also participates in tumor progression ( Su et al., 2017 ). It was shown that CD74, as an interferon gamma response gene, was a prognostic risk marker related to immune infiltration of LUAD ( Yao et al., 2021 ). CD74 interacted with CD44 and enhanced the occurrence and metastasis of breast cancer through RHOA-mediated cofilin phosphorylation ( Liu et al., 2016 ).…”