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Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite curative surgical resection, high recurrence of HCC after surgery results in poor patient survival. To develop prognostic markers is therefore important for better prevention and therapy of recurrent HCC to improve patient outcomes. Deletion mutations over the pre-S1 and pre-S2 gene segments of hepatitis B virus (HBV) have been closely associated with recurrence of HCC after curative surgical resection. In this study, we applied a next-generation sequencing-based approach to further evaluate the association of pre-S deletion regions with HCC recurrence. We demonstrated that the pre-S2 deletion (nucleotide 1 to 54) was the most predominant deletion regions of pre-S gene in plasma of HBV-related HCC patients. Moreover, patients with the pre-S2 deletion (nucleotide 1 to 54) exhibited a significantly higher risk of HCC recurrence after curative surgical resection than those without. The pre-S2 deletion (nucleotide 1 to 54) in plasma represented a prognostic factor that independently predicted HCC recurrence with greater performance than other clinicopathological and viral factors. Our data suggest that detection of the pre-S2 deletion (nucleotide 1 to 54) in plasma may be a promising noninvasive strategy for identifying patients at high risk for HCC recurrence after curative surgical resection.
Highlights
Among the most common and deadly human cancers worldwide, hepatocellular carcinoma (HCC) accounts for at least 700,000 deaths annually [1,2,3]
We further evaluated the association between deletion regions of pre-S mutants and HCC recurrence in a cohort of 75 hepatitis B virus (HBV)-related HCC patients receiving curative surgical resection
Median (Range) 53 (26–78) 60 (51–78) 43 (26–50) 26.9 (6.8–161.1)f aHBV DNA was measured with a detection range of 20 to 1.7×108 copies/mL. bAFP was measured with the highest detection limit of 54000 ng/mL. c,dOnly data within the detection range were analyzed. eShown was the time to recurrence after surgery. fShown was survival time in patients who died after surgery
Summary
Among the most common and deadly human cancers worldwide, hepatocellular carcinoma (HCC) accounts for at least 700,000 deaths annually [1,2,3]. Two types of GGHs (designated type I and II) are identified to consistently express the pre-S1 and pre-S2 mutant proteins, respectively, which contain deletion mutations in the pre-S1 and pre-S2 gene segments of HBV large surface proteins [14, 15]. Both types of pre-S mutants have been well demonstrated to dysregulate various oncogenic signaling pathways, leading to tumorigenesis of hepatocytes and eventually HCC development [13, 16,17,18].
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