COL1A1, COL1A2, COL3A1 and DCN are Potential Biomarkers to Predict Progression from Smokers to Suffering from Lung Adenocarcinoma

Abstract Background: To explore novel related genes and potential biomarkers that predict progression from smokers to lung adenocarcinoma (LA). Methods: Three datasets from GEO (Gene Expression Omnibus) database were used to identify differentially expressed genes (DEGs) between LA tissue (LAT) and normal tumor adjacent tissue (TAT). The overlap of DEGs could be found and enriched in gene oncology (GO) and pathways to discover the potential biological mechanisms. Protein-protein interaction (PPI) network was applied to find the relationship among proteins. Survival analysis contributed to the definiteness of key genes. The expression of key genes in LA patients who smoke was verified. Furthermore, genetic alterations, co-expression and pathways of key genes were explored. To obtain more information, key genes were further analyzed in immune infiltration, drug target and the distribution of single cell in LA. Results: 245 DEGs were revealed in 3 datasets from GEO. In Kaplan Meier plotter, we found that high expression of COL1A1, COL1A2 and COL3A1 was associated with poorer survival while low expression of DCN was contributed to poorer survival in LAs who smoke. Thus, three up-regulated genes (COL1A1, COL1A2, COL3A1) and one down-regulated gene (DCN) were defined as key genes. Their genetic alterations were more common in female LA smokers and co-expression genes/proteins of them mainly functioned at extracellular matrix. Furthermore, COL1A1, COL1A2, COL3A1 genes had a common targeted drug called Collagenase clostridium histolyticum (DB00048) and DCN gene had a targeted drug called Tromethamine (DB03754). In the Single Cell Expression Atlas of EMBL-EBL, COL3A1 gene was specifically highly expressed in female LA patients with brain metastasis. Conclusions: COL1A1, COL1A2, COL3A1 and DCN could be regarded as novel potential biomarkers that predict progression from smokers to lung adenocarcinoma.