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

• Published in: Technology in cancer research & treatment 2022-01, Vol.21, p.15330338221144510-15330338221144510
• Main Authors: Huang, Fei, Yang, Guowei, Jiang, Huiqin, Chen, Xinning, Yang, Yihui, Yu, Qian, Pan, Baishen, Wang, Beili, Guo, Wei, Yang, Wenjing, Zhang, Chunyan
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - pathology; Cell Proliferation - genetics; Hepatocellular carcinoma; Humans; Liver cancer; Liver diseases; Liver Neoplasms - pathology; Methylation; Microvasculature; Neoplasm Invasiveness; Plasma; Retrospective Studies; Screening, diagnosis, and treatment of hepatocellular carcinoma; Tumors; Vitamin K
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/15330338221144510

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.