Assessing the Prognostic Capability of Immune-Related Gene Scoring Systems in Lung Adenocarcinoma

Abstract

Background. Lung adenocarcinoma (LUAD) is the commonest of the subtypes of lung cancer histologically. For this study, we intended to analyze the expression profiling of the immune-related genes (IRGs) from an independently available public database and developed a potent signature predictive of patients’ prognosis. Methods. Gene expression profiles and the clinical data of lung adenocarcinoma were gathered from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), and the obtained data were split into a training set (n = 226), test set (n = 83), and validation set (n = 400). IRGs were then gathered from the ImmPort database. A prognostic model was constructed by analyzing the training set. Then the GO and KEGG analysis was performed, and a gene correlation prognostic nomogram was constructed. Finally, external validation, such as immune infiltration and immunohistochemistry, was performed. Results. The 110 genes were significant by univariate Cox regression analysis and randomized survival forest algorithm for the training set and showed a good distinction between the low-risk-score and high-risk-score groups in the training set ( P < 0.0001 ) by screening for four prognosis-related genes (HMOX1, ARRB1, ADM, PDIA3) and validated by the test set GSE30219 ( P = 0.0025 ) and TCGA dataset ( P = 0.00059 ). Multivariate Cox showed that the four gene signatures were an individual risk factor for LUAD. In addition, the genes in the signatures were externally verified using an online database. In particular, PDIA3 and HMOX1 are essential genes in the prognostic nomogram and play an important role in the model of immune-related genes. Conclusion. Four immune-related genetic signatures are reliable prognostic indicators for patients with LUAD, providing a relevant theoretical basis and therapeutic rationale for immunotherapy.

Metabolic and senescence characteristics associated with the immune microenvironment in non-small cell lung cancer: insights from single-cell RNA sequencing

“…KRT6A has been reported to be a negative regulator in NSCLC survival [ 27 ], which was in agreement with our analysis. An isolated study based on transcriptome data also validated the efficacy of ADM as an independent prognosis factor [ 28 ]. Here we exemplified that ADM was a key clinical factor in evaluating NSCLC survival at the single-cell level.…”