Prognostic and diagnostic value of SOX9 in cirrhotic and noncirrhotic hepatocellular carcinoma

Background: This study was designed to explore the prognostic and diagnostic value of Sex-Determining Region Y-Box 9 (SOX9) in cirrhotic hepatocellular carcinoma HCC (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). Methods: SOX9 tissue expression was detected using data from The Cancer Genome Atlas (TCGA) database and our cohort. The Kaplan-Meier method was used to analyze differences in survival between high/low SOX9 expression groups. Univariate analysis and multivariate analysis were used to identify independent risk factors associated with overall survival (OS). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were utilized for evaluation of the diagnostic efficacy of SOX9. Results: SOX9 was found to exhibit differential expression between HCC and adjacent normal tissues but not between CHCC and NCHCC, which was confirmed by RNA sequencing, quantitative real-time polymerase chain reaction and immunohistochemical staining. Kaplan-Meier survival analysis and multivariate analysis revealed that high SOX9 expression was closely related to the OS in NCHCC but not that in CHCC. In CHCC and NCHCC, SOX9 expression was positively associated with serum alpha-fetoprotein levels. The AUC of SOX9 in differentiating HCC and adjacent normal tissues in CHCC and NCHCC was 0.77 and 0.78, respectively, and no significant difference was found between them. Conclusions: High SOX9 expression may aid prognostic evaluation in NCHCC but not in CHCC. SOX9 expression was not different between CHCC and NCHCC, but it has reliable and comparable diagnostic value in both CHCC and NCHCC.