Weighted analysis of gene co-expression network identifies novel immune-associated hub genes for lung adenocarcinoma in elderly patients / 中华老年医学杂志

ABSTRACT

Objective:Immunologic characteristics of differed between younger and older patients.This study aimed to screen potentially key genes related to tumor-infiltrated immune cells(TIICs)in senile patients with lung adenocarcinoma(LUAD).Methods:In this retrospective study, the gene expression data for the training set were extracted from the Cancer Genome Atlas(TCGA)database, and the GSE72094 data set from Gene Expression Database was selected as the validation set.The 91 LUAD patients aged ≥75 years and 14 matched normal samples were screened for analysis.The components of tumor infiltrated immune cells(TIICs)were estimated by the deconvolution algorithm.Then a weighted gene co-expression network analysis was conducted in the training set so as to identify key genes correlating to TIICs.The GSE72094 dataset was used for validation.Results:In elderly patients with LUAD, the high expressions of IKZF1 and PRKCB were related to autoimmune diseases and T cell receptor signaling pathway.And their gene encoding proteins could interact with various immunomodulatory factors, such as IL2RB, LCK, and CD5.In the high expression group of IKZF1 and PRKCB, the expression levels of immunological checkpoint genes such as PD-L1, PD-1 and CTLA-4 were significantly higher than those of the low expression group(all P<0.01). The results of the validation set showed that CD8 + T cells were significantly correlated with the expression of IKZF1( r=0.75, P<0.01)and PRKCB( r=0.65, P<0.01). Conclusions:The expressions of IKZF1 and PRKCB in the tumor tissues are related to tumor infiltrating CD8 T cells and expression of immune checkpoint genes in elderly patients with LUAD.