New insights into COL26A1 in thyroid carcinoma: prognostic prediction, functional characterization, immunological drug target and ceRNA network.

Background: Thyroid carcinoma (THCA) is one of the most commonly diagnosed malignancies. Collagen is the main component in extracellular matrix. Rising studies have determined the oncogenic effect of collagen in cancer progression, which is intriguing to be further explored. Collagen type XXVI alpha 1 chain (COL26A1) is a newly discovered collagen subtype, functions of which still remain poorly demonstrated in THCA. Methods: Based on the transcriptome data from The Cancer Genome Atlas (TCGA) and other public databases, we conducted investigations of COL26A1 in THCA with respects to diagnostic/prognostic prediction, functional characterization, immune infiltration, chemical drug target and non-coding RNA regulatory network. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to verify the expression of COL26A1 in THCA. Results: COL26A1 was significantly upregulated in THCA, and the high COL26A1 expression inferred poor prognosis [hazard ratio (HR) =4.76; 95% confidence interval (CI): 1.36-16.73; P=0.015]. The diagnostic area under the curve (AUC) of COL26A1 achieved 0.736 (95% CI: 0.669-0.802). COL26A1 was also identified as an independent prognostic predictor for THCA (HR =3.928; 95% CI: 3.716-4.151; P<0.001). Besides, logistic regression analysis indicated that age >45 years [odds ratio (OR) =1.532; 95% CI: 1.081-2.176; P=0.017], pathological stage III (OR =2.055; 95% CI: 1.314-3.184; P=0.001), tall cell subtype (OR =5.533; 95% CI: 2.420-14.957; P<0.001), residual tumor R1 (OR =1.844; 95% CI: 1.035-3.365; P=0.041) and extrathyroidal extension (OR =1.800; 95% CI: 1.225-1.660; P=0.003) were risk factors associated with high COL26A1 expression in THCA. Functional characterizations implied that COL26A1 was associated with immunological processes and oncogenic signaling pathways. High COL26A1 expression was accompanied by more abundant infiltration of immune cells and higher stromal/immune score. In addition, most immune checkpoints were significantly positively co-expressed with COL26A1, including PD-1, PD-L1 and CTLA4. Drugs including trichloroethylene, acetamide and thioacetamide etc. that can decrease the expression of COL26A1 were also identified. The predicted long noncoding RNA (lncRNA)-microRNA (miRNA)-COL26A1 regulatory axes were successfully deciphered. qRT-PCR and western blot verified the upregulation of COL26A1 in THCA. Conclusions: Our work has primarily appraised COL26A1 as a promising biomarker for diagnosis/prognosis and immuno/therapeutic target in THCA.