The value of circulating methylated septin 9 in the diagnosis and prognostic assessment of gastric cancer.

Gastric cancer (GC) is a lethal malignancy usually diagnosed at advanced stages due to limited detection methods. Invasive examinations, such as electronic gastroscopy and pathological biopsy, have limitations for large-scale screening, while existing blood biomarkers (CEA, CA19-9, CA72-4) suffer from variable sensitivity and specificity. Methylated septin 9 (mSEPT9), a promising epigenetic biomarker in other cancers, remains understudied in GC. This retrospective study included 185 GC patients admitted to Shandong Cancer Hospital and Institute from January 2020 to December 2024. Clinical data were collected, and the levels of mSEPT9, conventional biomarkers (CEA, CA199, CA724), serum gastric function indicators (pepsinogen I [PG I], pepsinogen II [PG II], gastrin-17 [G-17]), and other indicators [cystatin S (CST4), and fecal occult blood (FOB)] were measured. Statistical analysis was performed using GraphPad Prism 9.0 and SPSS 23.0. Conventional biomarkers (CEA, CA19-9, CA72-4) correlated significantly with TNM staging and metastasis. The positive mSEPT9 associated with higher CA19-9 and CA72-4 levels, and enriched in advanced GC stage. Critically, serial assessments revealed that mSEPT9 sero-conversion events were temporally coupled with fluctuations in conventional biomarkers, suggesting a potential role in monitoring treatment response and predicting prognosis. In contrast, gastric function parameters, serum CST4 and FOB showed no significant correlation with TNM staging and were not useful for adjunctive GC diagnosis. mSEPT9 shows potential in GC diagnosis and prognosis prediction, and its combination with conventional biomarkers may improve the accuracy of GC diagnosis and prognosis assessment.