A First Step to a Biomarker of Curative Surgery in Colorectal Cancer by Liquid Biopsy of Methylated Septin 9 Gene.

M Leon Arellano,S Magallares,R Ruiz,M García-Arranz,T Valdes-Sanchez,D García-Olmo,S Olmedillas-Lopez,H Guadalajara,R Olivera

doi:10.1155/2020/9761406

M Leon Arellano, S Magallares + Show 7 more

Open Access

https://doi.org/10.1155/2020/9761406

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Abstract

Objectives To confirm that patients affected by colorectal cancer have the V2 region of Septin 9 (SEPT9) gene hypermethylated in the circulating free DNA from a peripheral blood sample before surgery and to determine if this hypermethylated DNA disappears from the patients after complete resection of the tumour. Methods Plasma from 10 patients with colorectal cancer was collected preoperative and three months after surgery. The analysis of the methylation status of the promoter region of the SEPT9 gene was performed using a 7500 Fast Real-Time PCR System. Results Hypermethylation of SEPT9 gene was detected in 8 out of 10 preoperative samples (one negative result was probed to be a Lynch syndrome) and in 4 out of 10 postoperative samples matching with the cases of recurrence or persistence of disease. This means that, in this sample, the preoperative sensitivity and specificity of the test were 88.9% and 100%, respectively, and there is 100% correlation between the positive results of the SEPT9 test and a recurrence/persistence of the disease in patients after surgical resection. Conclusions Our study shows that circulating hypermethylated SEPT9 is a specific colorectal cancer biomarker. This hypermethylated SEPT9 DNA disappears around three months after surgery and that circulating hypermethylated SEPT9 may be the first noninvasive marker for postsurgical diagnosis; this conclusion must be confirmed with a more significant number of patients.

Highlights

Colorectal cancer (CRC) is one of the most frequent tumours and almost the leading cause of deaths among cancer worldwide
The surgical approach is the best treatment for patients with CRC, but recurrence or persistence after resection is associated with a severe prognosis [1]
Patients included in the study must meet the following inclusion criteria: a confirmed diagnosis of colorectal cancer, surgical treatment of a tumour without the need for a posterior ostomy, no previous treatment of chemotherapy or radiotherapy, age between 50 and 75 years, and signed informed consent

Summary

Introduction

Colorectal cancer (CRC) is one of the most frequent tumours and almost the leading cause of deaths among cancer worldwide. Despite the development of new treatments, most patients are first-time diagnosed at the middle or late stage of CRC, leading to high mortality and a poor prognosis. The surgical approach is the best treatment for patients with CRC, but recurrence or persistence after resection is associated with a severe prognosis [1]. 25% to 40% of patients who undergo curative resection of colorectal cancer (CRC) develop tumour recurrence with eventual demise [2]. An optimal surveillance protocol for CRC includes CT scans, colonoscopies, and serum carcinoembryonic antigen (CEA) measurement, this blood marker has a reduced sensitivity or specificity. The primary objective of a surveillance protocol of CRC patients is to improve survival rates [4]

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