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

Abstract

Collagen type VI alpha 6 chain (COL6A6), 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 COL6A6 expression and its impact on survival among LUAD patients from The Cancer Genome Atlas (TCGA) and several other databases. COL6A6 was downregulated in LUAD tissues compared to normal tissues at both mRNA and protein levels. COL6A6 expression was negatively associated with pathological stage, tumor stage, and lymph node metastasis. High COL6A6 expression was a favorable prognostic factor in LUAD. Next, we explored the associations between COL6A6 expression and immune cell infiltration. COL6A6 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 COL6A6 gene copy number in LUAD. Consistently, gene set enrichment analysis showed that various immune pathways were enriched in the LUAD samples with high COL6A6 expression, including pathways related to T cell activation and T cell receptor signaling. The impacts of COL6A6 on immune activity were further assessed by enrichment analysis of 50 COL6A6-associated immunomodulators. Thereafter, using Cox regression, we identified a seven-gene risk prediction signature based on the COL6A6-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 COL6A6 is involved in tumor immunity, suggesting COL6A6 may be a potential immunotherapeutic target in LUAD. The proposed seven-gene signature is a promising prognostic biomarker in LUAD.

Comprehensive analysis of m7G modification patterns based on potential m7G regulators and tumor microenvironment infiltration characterization in lung adenocarcinoma

“…Correlation analysis of immune cell infiltration and m 7 Gscore ( Figure 6E ) indicated that m 7 Gscore was significantly positively correlated with most types of innate immune cells (e.g., eosinophil, dendritic cell, mast cell) and B cell, whereas negatively correlated with active CD4 T cell and CD56dim NK cell. In addition, m 7 Gscore was negatively correlated with immunosuppression-related ICGs (including IDO1, PDCD1, LAG3, TNFRSF9), whereas positively correlated with CD28 − CD80/86 ( Figure 6F ) which provides co-stimulatory signals for T-cell activation ( Esensten et al, 2016 ; Ma et al, 2021a ). Considering the above results, high m 7 Gscore indicated increased immune and stromal cell infiltration, while low m 7 Gscore was correlated with decreased immune cell infiltration and great immunosuppression.…”

Differential expression of COL6 family is a potential tumor marker for predicting gastric cancer

“…USP3 promotes gastric cancer progression and metastasis by deubiquitinating COL9A3 and COL6A5 [23]. COL6A6 has also been found to be a promoter gene in the lung [24], breast [25], and ovarian cancers [26]. However, there are few reports on the progress of studies on COL6A4P1, COL6A4P2, COL6A6 in gastric cancer.…”

Unveiling Collagen’s Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications

“… 110 Its expression is inversely associated with pathological stage, tumor stage, and lymph node metastasis. 111 Furthermore, COL6A6 causes retinitis pigmentosa in patients with autosomal dominant transmission. 112 Research have suggested that COL6A6 inhibits the progression of cancer cells through the JAK signaling pathway and PI3K-Akt pathway and is positively associated with the infiltration of B cells, T cells, neutrophils and dendritic cells.…”