Development of the prognostic value in lung adenocarcinoma based on anoikis‐related genes and initial experimental validation

Abstract

AbstractBackgroundLung adenocarcinoma (LUAD) is a highly aggressive cancer in advanced stages and has the highest cancer‐related death across the world. Anoikis has emerged as a specific form of apoptotic cell death that may play a vital role in the formation and development of tumors.MethodsBased on The Cancer Genome Atlas dataset, we developed a novel anoikis‐related genes (ARGs) signature in LUAD and evaluated the differences between low and high‐risk groups in clinical characteristics, expression patterns, immune cell infiltration, and drug sensitivity, etc. According to multivariate Cox regression analysis, the risk score was identified as a significant independent prognostic factor. The possible biological pathways of ARGs' were assessed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The immune infiltration landscape and risk score of ARGs were analyzed by ESTIMATE and CIBERSORT analysis. A nomogram grounded on six key ARGs and clinicopathological features was provided. Moreover, experiment validation of the expression patterns of six hub ARGs in lung cancer cell lines was conducted.ResultsWe identified 53 survival‐related LUAD anoikis‐related differentially expressed genes and finally six hub anoikis genes (LDHA, SLC2A1, SERPINB5, ITGB4, BRCA2, and PIK3R1) were selected to construct an ARG model. The risk model could efficiently cluster the patients into low‐ and high‐risk groups which could accurately predict clinical outcomes for LUAD patients. There is evidence that the prognostic risk score is a remarkable prognostic factor in determining overall survival. Different immune statuses and drug sensitivity between low‐ and high‐risk groups were explored according to functional analysis. On the basis of risk scores and LUAD clinicopathological features, a novel nomogram was developed. Ultimately, all six key genes except for PIK3R1 were proved to be upregulated in LUAD tissues and cell lines by bioinformatics analysis and experimental validation.ConclusionsThe result of the present study suggest that ARGs could be carcinogenic to LUAD and could be used as an effective stratification factor to customize therapies and forecast the survival rate in LUAD patients.