Diagnostic Value of Plasma Septin9 Methylation Combined with Multi-indicator Detection in the Progression of Primary Liver Cancer

Objectives To evaluate the diagnostic value of plasma methylated Septin9 (mSEPT9) combined with tumor markers and immunohistochemical (IHC) markers in the identification of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was conducted on a cohort of patients who had undergone mSEPT9 gene testing. Statistical analyses were performed using SPSS26.0 statistical software. The mSEPT9 and IHC indexes were analyzed using ggplot2 in the R package. Results The positivity rate of mSEPT9 in the HCC group (60.47%) was significantly higher than that in ICC groups [ICC (48.33%) vs the benign liver lesion group (2.04%) vs the HC group (1.30%)]. Moreover, mSEPT9 positivity rates in stages I, II, and III of the HCC group were 40.57%, 66.41% and 81.25%, respectively ( P  < 0.05). The results of IHC suggested that co-expression of Hep, Arg, and Ki67 was significantly higher in the mSEPT9-positive HCC subgroup compared to the mSEPT9-negative subgroup (12.5% vs. 3.4%, P  < 0.001). Likewise, in the ICC group, co-expression of GPC-3, Hep, Arg, and Ki67 was significantly higher in the mSEPT9-positive subgroup compared to the mSEPT9-negative subgroup (8.4% vs. 1.6%, P  < 0.001). Conclusion mSEPT9 demonstrated higher sensitivity in HCC patients, followed by AFP. In ICC patients, CA19-9 exhibited superior diagnostic value than mSEPT9. Additionally, the positivity rate of mSEPT9 was associated with HCC severity but not with ICC staging. MSEPT9 expression was also associated with IHC indicators, suggesting that epigenetic modifications may influence the expression of various proteins. Taking together, these findings provide a new direction for more accurate diagnosis and personalized treatment strategies for HCC, although further in-depth studies are warranted.