Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer

Sun, Jie; Xu, Jinling; Sun, Chao; Zheng, Minying; Li, Yuwei; Zhu, Siwei

doi:10.3389/fmolb.2021.568818

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…In our study, 94 CRC patients in stage II and III were analyzed by combining mSEPT9. 38.3% of patients underwent local recurrence or distant metastasis at the 2-year follow-up, consistent with the previous report [ 23 ]. Our results confirmed that mSEPT9 was an independent prognosis marker for CRC patients in stage II and III.…”

Section: Discussionsupporting

confidence: 90%

“…Based on mSEPT9, stage II and III patients could be further classified to provide a basis for individualized adjuvant therapy. Previous studies only simply found that the status of mSEPT9 before surgery was associated with survival of CRC patients [ 22 , 23 ], lacked in-depth understanding of its specific role. We stratified stage II and III patients in detail using mSEPT9 and clearly demonstrated the role of mSEPT9 in survival outcomes for the first time.…”

Section: Discussionmentioning

confidence: 99%

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Methylated septin 9 gene is an important prognostic marker in stage II and stage III colorectal cancer for evaluating local recurrence or distant metastasis after surgery

Huang

Wei

et al. 2022

BMC Gastroenterol

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Background Abnormal hypermethylation of the septin 9 gene was an inchoate incident in some cancers. Though latest several researches had paid attention to its value in prognosis, the consequences were not distinctly, especially in colorectal cancer (CRC) with stage II and stage III. Purpose The aim of this research was to pick up the prognostic value of the methylated septin 9 gene (mSEPT9) in CRC patients, particularly in TNM stage II—III. Methods Blood samples before surgery were obtained from 144 CRC patients, of which there were 94 with stage II and stage III. mSEPT9 was considered positive when the cycle number of the peak reaction (Ct) was lower than the threshold value (41.0) for two times during three times PCR test. mSEPT9 and other relative factors of prognosis were estimated by survival analysis. The level of septin 9 in tissues was tested by immunohistochemical (IHC). Results Stage II and stage III patients with mSEPT9 positive (mSEPT9+) had a lower disease-free survival (DFS) rate than those with mSEPT9 negative (mSEPT9-) (2-year DFS rates, 52.1% vs 73.9%, P = 0.014). In multivariate regression analysis, mSEPT9 was also an independent predictor of prognosis (HR = 2.741, P = 0.009). The risk of local recurrence or distant metastasis in CRC patients after surgery was mSEPT9+ with stage III, mSEPT9- with stage III/mSEPT9+ with stage II, and mSEPT9- with stage II (P = 0.001), from highest to lowest. In addition, mSEPT9 was strongly associated with TNM staging, tumor immersion depth, distant metastasis, differentiation degree, vascular invasion and microsatellite. When we explored the associations between septin 9 protein level revealed by IHC and other elements, recurrence/progression (R = − 0.523, P = 0.001), mSEPT9 status (R = − 0.451, P = 0.004) and T stage (R = − 0.375, P = 0.017) showed significant correlations. Conclusions Positive mSEPT9 is a poor prognostic marker for CRC patients in stage II and III. It is also a powerful complement to TNM staging in predicting postoperative DFS of CRC patients of stage II and III.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Methylated septin 9 gene is an important prognostic marker in stage II and stage III colorectal cancer for evaluating local recurrence or distant metastasis after surgery

Huang

Wei

et al. 2022

BMC Gastroenterol

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“…These studies have generally reported a 2‐ to 3‐fold increase in risk of recurrence. There are other studies reporting on the prognostic value of methylation‐based detection of ctDNA but their estimates arose from testing before commencing treatment 46,47 …”

Section: Discussionmentioning

confidence: 99%

“…There are other studies reporting on the prognostic value of methylation-based detection of ctDNA but their estimates arose from testing before commencing treatment. 46,47 At this point in time, there is no gold-standard for diagnosing the presence of minimal residual disease (MRD) and we are dependent on subsequent clinical course to identify those cases where disease has not been eradicated. There is a considerable amount of literature reporting the utility of somatic mutation-and/or epigenetic-based detection of ctDNA after surgical resection to identify those patients might benefit the most from adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Detection of methylated BCAT1 and IKZF1 after curative‐intent treatment as a prognostic indicator for colorectal cancer recurrence

et al. 2022

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Background:The risk of recurrence after completion of curative-intent treatment of colorectal cancer (CRC) is hard to predict. Post-treatment assaying for circulating tumor DNA (ctDNA) is an encouraging approach for stratifying patients for therapy, but the prognostic value of this approach is less explored. This study aimed to determine if detection of methylated BCAT1 and IKZF1 following completion of initial treatment identified patients with a poorer recurrence-free survival (RFS).Methods: 142 CRC stage I-III cases with at least 2 years of follow up (unless recurrence was evident sooner) and a methylated BCAT1/IKZF1 test result between 2 weeks and 12 months after completion of initial treatment were eligible for study inclusion. The association between BCAT1/IKZF1 and RFS was assessed by the log-rank (Mantel-Cox) method. Cox proportional hazard regression analysis was used for multivariable survival analysis.Results: Thirty-three (23.2%) had recurrence at a median 1.6y (interquartile range: 0.8-2.4). Methylated BCAT1/IKZF1 was detected in 19 of the 142 patients (13.4%) and was associated with a significant risk of recurrence (hazard ratio [HR] 5.7, 95%CI: 1.9-17.3, p = 0.002). Three-year RFS for patients with or without detectable methylated BCAT1/IKZF1 was 56.5% and 83.3%, respectively.Multivariable analysis showed that detection of methylated BCAT1/IKZF1 (HR = 2.6, p = 0.049) and site of the primary tumor (HR = 4.2, p = 0.002) were the only significant prognostic indicators of poor RFS.Conclusions: BCAT1/IKZF1 methylation testing after curative-intent treatment is an independent prognostic indicator for RFS and identifies a subgroup at high risk. Personalized surveillance is warranted for patients with these ctDNA biomarkers detectable after curative-intent treatment.

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“…Recently, studies have shown that mSEPT9 represents a promising biomarker for CRC detection. Studies have shown that the rate of SEPT9 methylation in peripheral blood of patients with CRC is related to clinicopathological features; for example, SEPT9 methylation is positively correlated with the malignancy of CRC [11][12][13]. After radical resection of colorectal cancer, the level of mSEPT9 in peripheral blood decreases; however, the level increases after recurrence, suggesting that mSEPT9 in peripheral blood can be used for evaluating the pathological stages of CRC and may represent a molecular biological indicator for evaluating prognosis, recurrence, and metastasis [14,15].…”

Section: Introductionmentioning

confidence: 99%

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer

Zhu

Song

et al. 2022

Disease Markers

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Purpose. The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods. Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results. mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion. Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.

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Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer

Cited by 11 publications

References 34 publications

Methylated septin 9 gene is an important prognostic marker in stage II and stage III colorectal cancer for evaluating local recurrence or distant metastasis after surgery

Methylated septin 9 gene is an important prognostic marker in stage II and stage III colorectal cancer for evaluating local recurrence or distant metastasis after surgery

Detection of methylated BCAT1 and IKZF1 after curative‐intent treatment as a prognostic indicator for colorectal cancer recurrence

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer

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