SEPT9 Gene Methylation as a Noninvasive Marker for Hepatocellular Carcinoma

Abstract

Background. Early detection appears to be the most effective approach to improve the overall survival of patients with hepatocellular carcinoma (HCC). We evaluated the potential performance of plasma SEPT9 methylation (mSEPT9) as a noninvasive biomarker for the diagnosis of patients with HCC. Methods. A total of 373 subjects were included, and the group consisted of 104 HCC patients, 95 with an at-risk disease, and 174 healthy controls (HC). The methylation of mSEPT9 was determined using methylation-specific fluorescence quantitative PCR. The diagnostic performance of plasma mSEPT9 for HCC was assessed in a single-blind manner. Results. The receiver operating characteristic (ROC) curve showed that plasma mSEPT9 can be used to detect and discriminate HCC with an area under the ROC curve (AUROC) of 0.961, a sensitivity of 82.7%, and specificity of 96.0% from HC. These results showed that plasma mSEPT9 had better diagnostic performance than serum alpha fetoprotein (AFP) (AUROC 0.881, sensitivity 57.7%, and specificity 98.3%). Similar results were noted in the detection of early-stage HCC. When combined with serum AFP, the sensitivity increased to 91.3% and 87.7% for the detection of HCC and early-stage HCC,respectively. Notably, the levels of plasma mSEPT9 dramatically decreased after surgery ( P = 0.001 ). Conclusions. Plasma SEPT9 methylation might serve as a useful and noninvasive biomarker for the diagnosis of HCC and can be used to evaluate the therapeutic efficacy of HCC treatment.

Methylated Septin9 (mSEPT9): A Promising Blood-Based Biomarker for the Detection and Screening of Early-Onset Colorectal Cancer

“…It is possible that mSEPT will perform even better in optimal clinical screening settings. Furthermore, we were able to quantitatively measure mSEPT in non-colorectal cancer cell lines, suggesting that mSEPT may have applicability as a biomarker in other cancer types, recent data suggests this to be the case for esophageal, gastric, and liver cancer (51,52). Future studies could focus on a pan-cancer evaluation of mSEPT combined with organ-specific markers to distinguish the biomarker origin.…”

The Prognostic Biomarkers and Immunotherapeutic Targets of Septin in Colon Cancer

“…And there was reported that SEPT7 and SEPT2 could synergically promote the proliferation, migration and invasion of breast cancer cells [38]. SEPT9, the most well-known member of the Septin family, has been studied for many years, with much emphasis on methylation and cancer biomarkers [39][40][41]. SEPT9 methylation analysis has great potential and usefulness as a non-invasive marker for early colon cancer, and might be used in combination with other conventional markers to detect disease recurrence [42,43].…”

Liquid Biopsy Using Cell-Free or Circulating Tumor DNA in the Management of Hepatocellular Carcinoma

“… 37 In particular, when combined with the serum α-fetoprotein (AFP) level, the sensitivity of HCC detection can be improved from 82.7% to 91.3%. 38 In addition, CDKN2A , CDKN2B , RASSF1A , STEAP4 , TBX2 , VIM , and ZNF154 are genes reported by previous studies that their serum DNA methylation was associated with HCC development and progression. 39 , 40 , 41 Wen et al 42 found that 4 genes, RGS10 , ST8SIA6 , RUNX2 , and VIM , are hypermethylated in HCC, which could be applied in HCC detection clinically.…”