Role of COL5A1 in lung squamous cell Carcinoma: Prognostic Implications and therapeutic potential.

Background: Lung squamous cell carcinoma (LUSC) is a significant health concern, characterized by a lack of specific therapies and limited treatment options for patients in advanced stages. This study aims to identify key molecules of prognostic importance in LUSC and provide an experimental foundation for their potential therapeutic applications.

Methods: Immune-related transcriptome expression analysis was performed on LUSC samples using the NanoString digital gene analysis system to develop a prognostic transcriptomic signature. This was followed by validation within the LUSC cohort database, and the immune properties and cellular functions of the critical molecule were examined through molecular biology experiments.

Results: Advanced nCounter analysis revealed significant differences in the numbers of T cells, cytotoxic cells, B cells, and CD45 and CD8 T cells between the OS1 (short-term survival) group and the OS2 (long-term survival) group. A comparison of the differences in tumor immune-related pathways between the two groups revealed that signaling pathways such as the PI3K-AKT, NF-kappaB signaling, Notch signaling, angiogenesis, matrix remodeling, and metastasis pathways were activated in the OS1 subgroup, and DNA damage repair and lymphatic chamber signaling pathways were activated in the OS2 subgroup. We analyzed and compared differentially expressed mRNAs with high expression levels in the OS1 and stage IV groups. Collagen type V alpha 1 (COL5A1) was found to be associated with the prognosis of LUSC. Phenotypic analysis revealed that COL5A1 knockdown inhibited the proliferation, migration, and invasion of SKMES1 cells. Locating COL5A1 was shown to be expressed in CAFs, T cells, and EPI cells through single-cell omics analysis.

Conclusion: COL5A1 plays a crucial role in tumor progression, indicating that COL5A1 inhibitors may represent a promising therapeutic strategy for the treatment of LUSC.