Tumor Purity Coexpressed Genes Related to Immune Microenvironment and Clinical Outcomes of Lung Adenocarcinoma.

Abstract

Purpose Lung cancer tissue includes tumor tissue, stromal cells, immune cells, and epithelial cells. These nontumor cells dilute the tumor purity in lung cancer tissues. Tumor purity plays an essential role in the immune response to lung cancer. At present, the biological processes related to the purity of lung cancer tumors remains unclear. Methods We measured tumor purity in 486 lung carcinoma tissues from TCGA-LUAD FPKM by using the “estimate” R package. Lung carcinoma tumor mutation burden was calculated by analyzing TCGA single nucleotide polymorphism data. The immune cell proportion was also evacuated via the CIBERSORT method. Lung carcinoma samples with P < 0.05 were considered significant. Based on the tumor purity and lung carcinoma gene matrix, we performed weighted gene coexpression network analysis (WGCNA), and the tumor purity-related module was identified. Then, we analyzed the functions of the factors involved in the module. We screened the coexpressed factors related to clinical outcome and immunophenotype. Finally, expression levels of these factors were measured at tissue and single-cell levels. Results A lung cancer tumor purity correlated coexpression network was determined. Five coexpressed genes (CD4, CD53, EVI2B, PLEK, and SASH3) were identified as tumor purity coexpressed genes that negatively correlated with tumor purity. Because the factors in the coexpression network often participate in similar biological processes, we found that CD4, CD53, EVI2B, PLEK, and SASH3 were most related to positive regulation of cytokine production and interleukin−2 production through functional enrichment. In a clinical phenotype analysis, we found that these five factors can be used as independent prognostic risk factors. We found that these factors were significantly negatively correlated with tumor purity and positively correlated with the immune score in the immunophenotyping analysis. Using GSEA analysis, we found that the antigen processing and presentation pathway were related to the five tumor coexpressed genes mentioned above. SASH3 and CD53 were used to conduct a prognostic model based on the interaction analysis of the Support Vector Machine and the Least Absolute Shrinkage and Selection Operator. SASH3 was verified to be related to CD8A using a single-cell analysis. Conclusion Tumor purity-related coexpression factors in the tumor microenvironment have essential clinical, genomic, and biological significance in lung cancer. These coexpression factors (SASH3 and CD53) can be used to classify tumor purity phenotypes and to predict clinical outcomes.