Polymorphism in asparagine synthetase is associated with overall survival of hepatocellular carcinoma patients.

BACKGROUND: Recently, it is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients. It is also reported that activating transcription factor 6 (ATF6) expression is decreased in HCC patients. So in the present study, we explored the relationship between ASNS and ATF6, and whether ASNS expression was associated with HCC.

METHODS: ATF6 was over expressed in 3 HCC cell lines (HepG2, HepG2.2.15 and SMMC-7721). We then examined the mRNA levels of ASNS and ATF6 in 90 HCC patients, 77 chronic hepatitis B patients and 70 controls. We also genotyped 2 functional polymorphisms in ASNS in a case-control study.

RESULTS: The expression of ASNS was significantly elevated when ATF6 was over expressed. The expressions of these 2 genes were both decreased in HCC patients, and it was more significantly with ASNS. The mRNA levels of ASNS and ATF6 were positively correlated with each other. rs34050735 was associated with HCC in the case-control study (P = 0.003) and also an independent predictor of overall survival of HCC patients (P = 0.001).

CONCLUSIONS: Taken together, these findings indicated that rs34050735 in ASNS may associate with HCC and may be a promising biomarker of HCC.