Role of Plasma methylated SEPT9 for Predicting Microvascular Invasion and Tumor Proliferation in Hepatocellular Carcinoma

Abstract

Background: Methylated SEPT9 (mSEPT9) has a role in the occurrence and development of hepatocellular carcinoma (HCC). Here, we studied the significance of plasma mSEPT9 for predicting prognosis-associated pathological parameters in patients with HCC. Methods: We retrospectively analyzed data from 205 subjects, including 111 HCC patients, 53 patients with at-risk liver disease (ARD) and 41 healthy donors (HDs). Analysis of plasma mSEPT9 was performed using methylation-specific polymerase chain reaction. Levels of mSEPT9 among different groups were compared using a nonparametric Mann-Whitney U test or a one-way ANOVA test. Correlations between pretreatment plasma mSEPT9 and clinicopathological characteristics were analyzed using the Chi-square. Univariate and multivariate analyses were used to identify factors related to microvascular invasion (MVI). Performance of variables for MVI prediction was evaluated by receiver operating characteristics curve. Results: A specific increase of plasma mSEPT9 in HCC was found when compared with ARD and HDs (HCC vs ARD, P  =  1.1  ×  10−5 and HCC vs HDs, P   =  3.7  ×  10−10). Pretreatment plasma mSEPT9 was significantly correlated tumor number ( P  =  .004), tumor size ( P  =  4.6  ×  10−5), MVI ( P  =  .002) and Barcelona Clinic Liver Cancer stage ( P  =  .012). Levels of plasma mSEPT9 correlated significantly with Ki67 expression in tumor ( r  =  0.356, P  =  1.3  ×  10−4). Univariate and multivariate analyses showed that plasma mSEPT9 and serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) were independent predictors for MVI. A combination of these 2 markers exhibited a larger areas under the curve (areas under the curve [AUC]  =  0.72) than mSEPT9 or PIVKA alone (AUC  =  0.67 and 0.65), especially in early-stage HCC. Conclusions: Plasma mSEPT9 is a promising noninvasive biomarker for predicting MVI and tumor proliferation in HCC. Integration plasma mSEPT9 detection into clinical settings might facilitate the patient management.