Comprehensive Analysis of the Immune and Prognostic Implication of COL6A6 in Lung Adenocarcinoma

• Published in: Frontiers in oncology Vol. 11; p. 633420
• Main Authors: Ma, Yi, Qiu, Mantang, Guo, Haifa, Chen, Haiming, Li, Jiawei, Li, Xiao, Yang, Fan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26.02.2021
• Subjects: COL6A6; lung adenocarcinoma; nomogram; Oncology; prognosis; signature; tumor microenvironment; COL6A6; nomogram; tumor microenvironment; signature; prognosis; lung adenocarcinoma
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.633420

Collagen type VI alpha 6 chain ( ), a novel collagen, has been considered as a tumor suppressor and therapeutic target in several tumors. However, the functional role of COL6A6 in immune cell infiltration and prognostic value in lung adenocarcinoma (LUAD) remains unknown. Here, we evaluated expression and its impact on survival among LUAD patients from The Cancer Genome Atlas (TCGA) and several other databases. was downregulated in LUAD tissues compared to normal tissues at both mRNA and protein levels. expression was negatively associated with pathological stage, tumor stage, and lymph node metastasis. High expression was a favorable prognostic factor in LUAD. Next, we explored the associations between expression and immune cell infiltration. expression was positively associated with the infiltration of B cells, T cells, neutrophils and dendritic cells. Additionally, the immune cell infiltration levels were associated with gene copy number in LUAD. Consistently, gene set enrichment analysis showed that various immune pathways were enriched in the LUAD samples with high expression, including pathways related to T cell activation and T cell receptor signaling. The impacts of on immune activity were further assessed by enrichment analysis of 50 -associated immunomodulators. Thereafter, using Cox regression, we identified a seven-gene risk prediction signature based on the -associated immunomodulators. The resulting risk score was an independent prognostic predictor in LUAD. Receiver operating characteristic curve analysis confirmed that the seven-gene signature had good prognostic accuracy in the TCGA-LUAD cohort and a Gene Expression Omnibus dataset. Finally, we constructed a clinical nomogram to predict long-term survival probabilities, and calibration curves verified its accuracy. Our findings highlight that is involved in tumor immunity, suggesting may be a potential immunotherapeutic target in LUAD. The proposed seven-gene signature is a promising prognostic biomarker in LUAD.