High expression of COL8A1 predicts poor prognosis and promotes EMT in papillary thyroid cancer.

Background: Collagen type VIII α 1 chain (COL8A1), a collagen type VIII protein, has been suggested to exert various functions in progression of multiple cancers. However, the effect of COL8A1 in papillary thyroid cancer (PTC) has not been elucidated.

Methods: The Cancer Genome Atlas (TCGA) databases were applied to investigate the COL8A1 expression and its clinical significance in PTC. The COL8A1 expression level was further validated using Gene Expression Omnibus (GEO) data and clinical paired PTC tissues. Additionally, the Kaplan-Meier curve was used to analyze the prognosis. The cell's migrative and invasive abilities were evaluated by wound healing assay and Transwell assay. CCK8 assays were used to evaluate the proliferation of PTC cells. Western blotting was conducted to explore the potential mechanisms involved in the pro-tumor role of COL8A1. The correlation between immune cell infiltration and COL8A1 was analyzed using the Tumor Immune Estimation Resource (TIMER) database and the single-sample GSEA (ssGSEA) method.

Results: We found that COL8A1 was upregulated in PTC (P < 0.05). High COL8A1 expression level was significantly associated with advanced T stage (P < 0.01), N stage (P < 0.001) and poor prognosis (P = 0.0142) in PTC. Furthermore, cell migration and invasion were significantly reduced following COL8A1 knockdown (P < 0.001). Mechanistic studies demonstrated that the epithelial-to-mesenchymal transition (EMT) related proteins (FN1, MMP9, MMP7, ZEB2 and Twist1) and phosphorylation of AKT and ERK were obviously down-regulated after COL8A1 knockdown (P < 0.01). Moreover, COL8A1 expression was correlated with immune cell infiltration.

Conclusion: Our study demonstrates that COL8A1 may function as an oncogene and a potential prognostic biomarker for PTC patients.