Analysis of CAFs‑related Genes Identifies COL11A1 Associated with Lung Adenocarcinoma Diagnosis and Prognosis

Abstract Background Difficulties in the treatment of lung adenocarcinoma(LUAD) are due to lack of understanding of relevant molecular mechanisms and limited potential therapeutic options. Cancer-related fibroblasts(CAFs) play an important role in the occurrence and development of cancers. Therefore, this study aimed to identify a promising molecular target associated with CAFs for the diagnosis and prognosis of LUAD. Methods The Cancer Genome Atlas (TCGA) LUAD dataset was used to screen out the hub genes by EPIC algorithm and Weighted Gene Co-expression Network Analysis (WGCNA). GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, and GSE32863 were used to verify the differential expression and survival of hub genes. Immunohistochemistry (IHC) was used to assess the expression of COL11A1 in LUAD and adjacent normal tissues. GO/KEGG functional analyses and single-cell TISCH database were used to elucidate the underlying mechanisms of COL11A1. Results Based on the TCGA LUAD dataset, 13 hub genes associated with CAFs were screened out by the EPIC algorithm and WGCNA. These were ADAM12, ADAMTS12, COL11A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ITGA11, LRRC15, POSTN, THBS2, THY1. Using the GEPIA database, Kaplan-Meier Plotter database, GSE72094, GSE75037, and GSE32863, we confirmed that COL11A1 was overexpression in LUAD tumor tissues and high expression of COL11A1 had a poor prognosis. Using IHC experiment data, we confirmed that the expression of COL11A1 was significantly higher in LUAD (P < 0.001). We found that COL11A1 had a mutation frequency of 18% and COL11A1 promoter hypermethylation in LUAD (P < 0.05). Using GO/KEGG analyses, we found that COL11A1 was mainly related to the biological activities of the extracellular matrix in LUAD. Finally, in the TISCH database, we found that the expression of COL11A1 was mainly secreted by CAFs in the TME rather than from LUAD cells. Conclusion COL11A1 may be expressed and secreted by CAFs in the TME and affect the biological behavior of proliferation, invasion, and metastasis of LUAD cells. COL11A1 may serve as a potential diagnostic and prognosis biomarker for LUAD.