The Application Of Septin 9 Methylation In The Diagnosis, Therapeutic Evaluation And Recurrence Monitoring Of Colorectal Cancer

Objective:This study was to evaluate the clinical value of plasma methylated SEPT9 gene(mSEPT9)in diagnosis,therapeutic evaluation and monitoring recurrences of colorectal cancer(CRC).The level of methylation of septin 9 and the expression of SEPT9 protein in tissues of CRC and adenoma was also investigated.Methods:A total of 482 plasma subjects were enrolled in this study,including 98 samples with CRC,101 samples with adenoma,30 samples with inflammation and 253 subjects with no evidence of diseases.The number of 86 tissue subjects were coleected,including 56 samples with CRC,30 samples with adenoma.mSEPT9 was detected using real-time qPCR and bisulfite conversion.In total,60 tissue cases of the tumor samples were analysed by immunohistochemical staining for SEPT9,including 30 samples with positive mSEPT9 and 30 samples with negtive mSEPT9.Concentration of serum CEA was measured using the electrochemilu-minescence immunoassay.The patients were followed up for 2 years and reviewed every three months in the first year and every six months thereafter.Examinations included colonoscopy,CT or MRI of chest and abdomen,serum CEA and mSEPT9..Results:Our results confirmed the favorable diagnostic value of plasma mSEPT9 for CRC,with a sensitivity of 61.2%(95 %confidence interval(CI):51.3 %-70.3%)and specificity of 93.7%(95%CI:91.1%-95.6%).The positive rate of mSEPT9 in peripheral blood of colorectal cancer patients(61.2%)was significantly higher than that of patients with adenoma(7.9%),inflammatory patients(6.7%),and healthy controls(1.6%).The difference was statistically significant(P<0.001).While,there was also a very good diagnostic value in the organization,with a sensitivity of 76.8 %(95% confidence interval(CI):64.2%-85.9 %)and specificity of 86.67%(95%CI:70.3%-94.7%).The positive rate of tissue mSEPT9 in colorectal carcinoma(76.8%)was significantly higher than that of adenoma(13.3%),and the difference was statistically significant(P<0.001).The positive rate of plasma mSEPT9 in CRC was correlated with tumor size,histological grade,and general histological type(P<0.05).The positive rate of mSEPT9 in tissue was only related to histological grade,and the difference was statistically significant(P=0.037).The conversions between preoperative and postoperative plasma mSEPT9 reflected the therapeutic efficacy of curatively intended surgery for CRC patients.The persistent positivity of plasma mSEPT9 after surgery(within 7-14 days)was highly associated with impending recurrences or metastases.Conclusions:Our results verified the reliability of plasma mSEPT9 as a biomarker for noninvasive diagnosis of CRC.More significantly,we revealed its valuable role in appraising CRC therapeutic efficacy and monitoring CRC recurrences or metastases.Further studies with larger sample sizes are needed to verify and elucidate the clinical utility of the promising findings.