Clinica chimica acta; international journal of clinical chemistry · 2026
Methylated Septin9 as an auxiliary biomarker for the diagnostic, recurrence monitoring and prognosis of colorectal cancer.
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Wang Jiaxin, Li Ying, Liu Xuan, Gao Qian, Yi Lang
Аннотация
OBJECTIVE: The liquid biopsy biomarker "methylated Septin9 (mSEPT9)" has emerged as a prominent tool in colorectal cancer (CRC) screening. This study aims to explore the clinical significance of mSEPT9 in the diagnosis, evaluation of surgical efficacy, monitoring of recurrence, and prognostic assessment of colorectal cancer, while also comparing its performance with that of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).
MATERIAL AND METHODS: We conducted a retrospective cohort study using clinical data from Xiangya Hospital of Central South University (March 2017-November 2024). Three independent patient groups were identified: (1) Diagnosis group: 461 treatment-naïve patients with newly diagnosed colorectal cancer (CRC); (2) Post-treatment group: 72 patients with CRC who underwent curative-intent resection and had paired plasma mSEPT9 measurements preoperatively and at postoperative day 7; (3) Recurrence-monitoring group: 138 patients with AJCC stage I-III CRC who underwent curative resection, for whom recurrence-free survival (RFS) was the primary endpoint and for whom preoperative and postoperative month 1 (POM1) plasma mSEPT9 levels were available-associations between mSEPT9 and RFS were evaluated using Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression.
RESULTS: Plasma mSEPT9 detected CRC with 67.9% sensitivity (313/461) and 94.0% specificity in distinguishing patients from healthy controls (NED), yielding an AUC of 0.809, which was higher than that of CEA (0.692) and CA19-9 (0.584).The combination of mSEPT9, CEA, and CA19-9 achieved an AUC of 0.849 (P < 0.001 vs. mSEPT9 alone). Sensitivity increased with tumor stage: 22.2% (stage I), 65.2% (II), 66.2% (III), and 81.5% (IV). In the 72-patient post-treatment group, mSEPT9 positivity decreased from 61.1% preoperatively to 38.9% at 7 days postoperatively (P < 0.001). Among the 138 patients in the recurrence-monitoring group, 49 (35.5%) developed recurrence. Independent predictors of shorter RFS were POM1 mSEPT9 positivity (HR = 6.25, 95% CI: 3.29-11.88; P < 0.001), advanced N stage (HR = 3.43, 95% CI: 1.66-7.08; P = 0.001), perineural invasion (HR = 2.04, 95% CI: 1.08-3.85; P = 0.028), and preoperative CEA > 5 ng/mL (HR = 2.21, 95% CI: 1.06-4.61; P = 0.035). Patients positive for both POM1 mSEPT9 and preoperative CEA > 5 ng/mL had the shortest RFS (P < 0.001).For recurrence prediction, POM1 mSEPT9 achieved an AUC of 0.721 (sensitivity 51.0%, specificity 93.3%), POM1 CEA yielded an AUC of 0.616 (sensitivity 26.5%, specificity 96.6%), and their combination resulted in an AUC of 0.725.
CONCLUSION: The mSEPT9 can be used as a sensitive and efficient indicator for CRC diagnosis and surgical efficacy evaluation, outperforming both CEA and CA19-9. A combined panel of mSEPT9, CEA, and CA19-9 was shown to achieve superior diagnostic performance compared to mSEPT9 alone. More significantly, our findings highlight the significant value of mSEPT9 in monitoring postoperative recurrence and metastasis in CRC patients. Specifically, mSEPT9 detection at one month after surgery could be an independent predictor, capable of predicting the recurrence or metastasis of CRC.
MATERIAL AND METHODS: We conducted a retrospective cohort study using clinical data from Xiangya Hospital of Central South University (March 2017-November 2024). Three independent patient groups were identified: (1) Diagnosis group: 461 treatment-naïve patients with newly diagnosed colorectal cancer (CRC); (2) Post-treatment group: 72 patients with CRC who underwent curative-intent resection and had paired plasma mSEPT9 measurements preoperatively and at postoperative day 7; (3) Recurrence-monitoring group: 138 patients with AJCC stage I-III CRC who underwent curative resection, for whom recurrence-free survival (RFS) was the primary endpoint and for whom preoperative and postoperative month 1 (POM1) plasma mSEPT9 levels were available-associations between mSEPT9 and RFS were evaluated using Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression.
RESULTS: Plasma mSEPT9 detected CRC with 67.9% sensitivity (313/461) and 94.0% specificity in distinguishing patients from healthy controls (NED), yielding an AUC of 0.809, which was higher than that of CEA (0.692) and CA19-9 (0.584).The combination of mSEPT9, CEA, and CA19-9 achieved an AUC of 0.849 (P < 0.001 vs. mSEPT9 alone). Sensitivity increased with tumor stage: 22.2% (stage I), 65.2% (II), 66.2% (III), and 81.5% (IV). In the 72-patient post-treatment group, mSEPT9 positivity decreased from 61.1% preoperatively to 38.9% at 7 days postoperatively (P < 0.001). Among the 138 patients in the recurrence-monitoring group, 49 (35.5%) developed recurrence. Independent predictors of shorter RFS were POM1 mSEPT9 positivity (HR = 6.25, 95% CI: 3.29-11.88; P < 0.001), advanced N stage (HR = 3.43, 95% CI: 1.66-7.08; P = 0.001), perineural invasion (HR = 2.04, 95% CI: 1.08-3.85; P = 0.028), and preoperative CEA > 5 ng/mL (HR = 2.21, 95% CI: 1.06-4.61; P = 0.035). Patients positive for both POM1 mSEPT9 and preoperative CEA > 5 ng/mL had the shortest RFS (P < 0.001).For recurrence prediction, POM1 mSEPT9 achieved an AUC of 0.721 (sensitivity 51.0%, specificity 93.3%), POM1 CEA yielded an AUC of 0.616 (sensitivity 26.5%, specificity 96.6%), and their combination resulted in an AUC of 0.725.
CONCLUSION: The mSEPT9 can be used as a sensitive and efficient indicator for CRC diagnosis and surgical efficacy evaluation, outperforming both CEA and CA19-9. A combined panel of mSEPT9, CEA, and CA19-9 was shown to achieve superior diagnostic performance compared to mSEPT9 alone. More significantly, our findings highlight the significant value of mSEPT9 in monitoring postoperative recurrence and metastasis in CRC patients. Specifically, mSEPT9 detection at one month after surgery could be an independent predictor, capable of predicting the recurrence or metastasis of CRC.