Genetic analyses of differences between solid and nonsolid predominant lung adenocarcinomas

Abstract

BackgroundSolid predominant lung adenocarcinomas (LUAD) have distinct histopathological and clinical characteristics compared with nonsolid subtypes. A comprehensive comparison of altered genes found in solid and nonsolid subtypes has not previously been performed. In this study, we analyzed differences in gene expression, genetic mutations, and DNA methylation to better understand the risk factors for these two subtypes of LUAD.MethodsDifferentially expressed genes (DEGs) and differentially mutated genes (DMGs) were analyzed from RNA‐seq data downloaded from The Cancer Genome Atlas (TCGA) and Broad Institute database. To understand the functional significance of molecular changes, we examined the DEGs and DMGs with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis.ResultsA total of 184 patients in the TCGA cohort and 140 patients in the Broad Institute cohort were included in this study. We identified 75 DEGs, of which 15 were upregulated and 56 downregulated in the solid group relative to the nonsolid group. The DEGs were mainly involved in the regulation of water and fluid transport. We discovered 38 significantly differentially expressed genes that overlapped in the two groups. The DMGs were mainly enriched for pathways involved in cell–cell adhesion, cell adhesion, biological adhesion, and hemophilic cell adhesion. We additionally discovered nine significantly methylated genes between solid and nonsolid LUAD.ConclusionsOur study identified distinct DEGs, DMGs, and methylation genes for solid and nonsolid LUAD subtypes. These findings improve our understanding of the different carcinogenesis mechanisms in LUAD and will help to develop new therapeutic strategies.

Analysis of the clinicopathological characteristics, genetic phenotypes, and prognostic of pure mucinous adenocarcinoma

“…Genome statistical analyses performed in R version 3.5.1 were as follows: (a) differentially expressed genes (DEGs) among all samples between the PMA and other LUAD patients were analyzed by using the DESeq2 package in R. The statistical threshold for significance was a false discovery rate <0.05 and fold change >2; (b) differentially mutated gene (DMG) analysis was performed between the PMA and other LUAD cohorts, and the frequency of gene mutation in all samples was determined by using the maftools package in R. The difference in the mutation ratio for each gene was identified with Fisher's exact test, and a P value < .05 was considered significant; (c) differentially methylated genes (DMeGs) were considered to be genes whose absolute differences in average methylation level between PMA and other LUAD cases were ≥0.15, with P < .05 in a Wilcoxon test. In our study, C‐phosphate‐G sites in which methylation was present in at least 80% of the samples were used to evaluate the methylation levels of expressed genes; (d) GO and KEGG analyses were performed with the clusterProfiler package in R to identify the main functions of the DEGs. A significant difference in Gene Ontology (GO) or KEGG pathways was defined as P < .05.…”

Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component

“…The characteristic biological mechanisms underlying SPA have been described, e.g., an invasive immunophenotype including increased laminin-5 expression, aggressive tumor microenvironment with higher immune evasion potential, and abundant stromal cells with tumor-promoting function [23,24]. Recently, several studies have reported the molecular profiles of SPA or SC in LUAD using tissue samples [14,15] or databases [16,17]. Zabeck et al identified inositol-1,4,5trisphosphate kinase A (ITPKA) as an upregulated gene in SC and angiogenin in the lepidic component (LC) [15].…”

“…Zabeck et al identified inositol-1,4,5trisphosphate kinase A (ITPKA) as an upregulated gene in SC and angiogenin in the lepidic component (LC) [15]. Luo et al reported that DEGs between SPA and non-SPA are mainly involved in the regulation of water and fluid transport [16]. Dong et al reported that the expression of PD-L1 is increased in SPA [17].…”

“…This prompted us to investigate the biological and molecular features of SC in patients with LUAD. Several recent studies have reported the specific gene expression profiles for lepidic predominant adenocarcinoma [13] or SPA [14][15][16][17]. However, to our knowledge, differentially expressed genes (DEGs) between the SC and acinar component (AC), which is also known as the most popular component among the histologic subtype of LUAD [3,9], within the same tumor tissue in patients with p-stage I LUAD have not been identified.…”