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

Fei Huang; Guowei Yang; Huiqin Jiang; Xinning Chen; Yihui Yang; Qian Yu; Baishen Pan; Beili Wang; Wei Guo; Wenjing Yang; Chunyan Zhang

doi:10.1177/15330338221144510

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

Technol Cancer Res Treat. 2022 Jan-Dec:21:15330338221144510. doi: 10.1177/15330338221144510.

Authors

Fei Huang¹, Guowei Yang², Huiqin Jiang¹, Xinning Chen¹, Yihui Yang¹, Qian Yu¹, Baishen Pan^{1

3}, Beili Wang¹, Wei Guo^{1

4

5

3

6}, Wenjing Yang¹, Chunyan Zhang^{1

6}

Affiliations

¹ 92323Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Interventional Radiology, 92323Zhongshan Hospital, Fudan University, Shanghai, China.
³ Branch of National Clinical Research Center for Laboratory Medicine, Shanghai, China.
⁴ Cancer Centre, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.

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.

Keywords: circulating tumor DNA; hepatocellular carcinoma; methylated SEPT9; microvascular invasion; tumor proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / metabolism
Carcinoma, Hepatocellular* / pathology
Cell Proliferation / genetics
Humans
Liver Neoplasms* / pathology
Neoplasm Invasiveness
Retrospective Studies

Substances

Biomarkers, Tumor