Abstract
Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment. Cox proportional hazard models were used for survival analysis with adjustments for the age, gender, smoking status, drinking status, Barcelona-Clinic Liver Cancer (BCLC) stage, and chemotherapy or TACE (transcatheter hepatic arterial chemoembolization) status. We found that the G allele of rs1110839 and the T allele of rs4848320 in PAX8was significantly associated with a better prognosis compared with the T allele of rs1110839 and the C allele of rs4848320 (adjusted HR = 0.74, 95% CI = 0.61–0.91, P = 0.004 for rs1110839 and adjusted HR = 0.71, 95% CI = 0.54–0.94, P = 0.015 for rs4848320 in the additive model). Furthermore, the combined effect of the variant genotypes for these two SNPs was more prominent in patients with the BCLC-C stage orpatients with chemotherapy or TACE. Although the exact biological function remains to be explored, our findings suggest a possible association of PAX8eQTLs in lncRNA AC016683.6 with the HCC prognosis inthe Chinese population. Further large and functional studies are needed to confirm our findings.
Highlights
Liver cancer is the fifth most common cancer worldwide and the third greatest cause of cancer-related death worldwide [1]
Compared to those who received neither chemotherapy nor TACE therapy (MST = 3.4 months), patients with chemotherapy or TACE therapy (MST = 16.8 months) had a significantly decreased risk of death (61%, hazard ratio (HR) = 0.39; 95% confidence intervals (CI) = 0.29–0.51)
In the present case-cohort study, we demonstrated that PAX8eQTLs may be an independent candidate biomarker for predicting Hepatocellular carcinoma (HCC) survival in Chinese with a prospective study design
Summary
Liver cancer is the fifth most common cancer worldwide and the third greatest cause of cancer-related death worldwide [1]. Hepatocellular carcinoma (HCC) is the most common type of liver cancer [2]. The Barcelona Clinic Liver Cancer (BCLC) staging classification has been widely endorsed to predict the prognosis of HCC patients; remarkably different survival outcomes among HCC patients at the same stage suggest that the existence of other important factors might affect the prognosis. This current status has inspired researchers to focus on identifying molecular biomarkers to guide individualized treatment and improve the prognosis of cancer patients. The potential role of PAX8 in HCC prognosis has been rarely explored
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