Expression quantitative trait loci for PAX8 contributes to the prognosis of hepatocellular carcinoma.
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.
Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Shijie
S
Ma
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Jianshui
J
Yang
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Ci
C
Song
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Zijun
Z
Ge
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Jing
J
Zhou
Departmentof Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Guoxin
G
Zhang
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing,China.
Zhibin
Z
Hu
D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000072636:PAX8 Transcription Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D040641:Quantitative Trait Loci; D015996:Survival Rate
D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human