COL3A1: Potential prognostic predictor for head and neck cancer based on immune‐microenvironment alternative splicing

Abstract

We aimed to identify a novel prognostic biomarker for head and neck squamous cell carcinoma (HNSCC) based on tumor immunology‐related alternative splicing (AS). Data for 502 HNSCC and 44 normal samples were obtained from the TCGA database and used to establish an AS‐related risk model through univariate, least absolute shrinkage, and selection operator Cox regression analyses. Fresh HNSCC and normal oral tissues were surgically obtained from 44 HNSCC patients. Western blotting and quantitative reverse transcription‐PCR were used to assess gene expression levels. Kaplan–Meier was performed to evaluate patients' overall survival (OS) rate. The CIBERSORT algorithm, single‐sample gene set enrichment analysis, and immune checkpoint analyses were performed to compare immune activities between subgroups. The risk model was established using 10 pivotal AS events first. Collagen Type III Alpha 1 Chain (COL3A1) were screened based on |log2FC| ≥ 1 and FDR < 0.05 criteria. COL3A1 expression levels in HNSCC tissues were elevated relative to normal tissues (p < 0.001). Moreover, COL3A1 was a reliable biomarker for HNSCC patients' prognostic prediction in both cohorts (p < 0.001, p = 0.0085, respectively). COL3A1 protein (p = 0.0054) and mRNA (p < 0.0001) levels were correlated with HNSCC differentiation. Furthermore, the T stage was correlated with COL3A1 expression (p = 0.043), and COL3A1 expression was an independent prognostic predictor for HNSCC patients (p = 0.006). Compared with the risk model, COL3A1 was better at evaluating immune cell infiltrations, immune activities, and immune checkpoint gene expressions of HNSCC lesions.

The lncRNA XIST/miR-29b-3p/COL3A1 axis regulates central carbon metabolism in head and neck squamous cell carcinoma and is associated with poor tumor prognosis

“…At present, there are few related studies on the role of COL3A1 in HNSCC. One study reported that COL3A1 has a good role in evaluating the immune cell infiltration, immune activity and gene expression of immune checkpoint of HNSCC lesions (28). At the same time, the head and neck are rich in connective tissue, so it is also of anatomical significance to study the role of COL3A1 in HNSCC.…”

Identification of Immune Infiltration in Odontogenic Keratocyst by Integrated Bioinformatics Analysis

“…Immune cells can intimately interact with stromal cells and further impact tumor progression, invasion, and metastasis. A study showed that patients with head and neck squamous cell carcinoma (HNSCC) with increased COL3A1 levels also had a higher level of resting CD4 + T cells and resting NK cells [ 35 ]. The expression of COL3A1 was associated with the increase of IL-1β in osteoarthritis and was also linked to immune cell infiltration [ 36 ].…”

Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells

“… 7 COL3A1 is also identified as a promising independent predictor for prognosis of head and neck cancer and colorectal cancer. 8 , 9 Abnormal expression of COL3A1 mediated by RNF185 exhibits a potent regulatory activity in the metastatic potential of prostate cancer. 10 Moreover, in triple negative breast cancer, knocking down COL3A1 plays a repressive role in cancer cell growth and metastasis depending on PD-L1 reduction.…”