Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2019; 25(17): 2099-2109
Published online May 7, 2019. doi: 10.3748/wjg.v25.i17.2099
Clinical value of preoperative methylated septin 9 in Chinese colorectal cancer patients
Xue Yang, Zhi-Jie Xu, Xi Chen, Shuang-Shuang Zeng, Long Qian, Jie Wei, Mei Peng, Xiang Wang, Wan-Li Liu, Hong-Ying Ma, Zhi-Cheng Gong, Yuan-Liang Yan
Xue Yang, Xi Chen, Shuang-Shuang Zeng, Long Qian, Jie Wei, Mei Peng, Xiang Wang, Wan-Li Liu, Hong-Ying Ma, Zhi-Cheng Gong, Yuan-Liang Yan, Department of Pharmacy, Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Zhi-Jie Xu, Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Yang X and Xu ZJ designed the research scheme and contributed equally to this article; Yan YL and Gong ZC contributed equally to correspondence about this manuscript; Chen X, Zeng SS, Qian L, and Wei J collected data from the samples; Peng M, Wang X, Liu WL, Xu ZJ, and Ma HY analyzed the data.
Supported by the National Natural Science Foundation of China, No. 81803035, No. 81703036, and No. 81572946; the China Postdoctoral Science Foundation, No. 2017M610510; and the Youth Fund of Xiangya Hospital, No. 2017Q17.
Institutional review board statement: This study was reviewed and approved by the Ethical Committee of Xiangya Hospital of Central South University (Approval No. 2018111100).
Informed consent statement: According to the “Human Biomedical Research Ethical Review Procedures” approved by the National Health and Family Planning Committee of China (No. 11, Section 39), informed consent was waived because of the retrospective nature of the study. After the following circumstances have been reviewed and approved by the ethics committee, the informed consent form can be waived if: Research is conducted using human body materials or data that can identify information, and the subjects can’t be found, and the research project does not involve personal privacy and commercial interests.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi-Cheng Gong, PhD, Professor, Department of Pharmacy, Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, Hunan Province, China. gongzhicheng@csu.edu.cn
Telephone: +86-731-84327306
Received: February 14, 2019
Peer-review started: February 15, 2019
First decision: March 5, 2019
Revised: March 25, 2019
Accepted: April 10, 2019
Article in press: April 10, 2019
Published online: May 7, 2019
Abstract
BACKGROUND

The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown.

AIM

To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients.

METHODS

A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal, was performed in China. Patients’ characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control (UICC) stages, distant metastasis (M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas (TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier univariate analysis.

RESULTS

In Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages (I–IV), primary tumor categories (T1–T4), regional node categories (N0–N2), and distant metastasis categories (M0–M1). The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.

CONCLUSION

MSEPT9 analysis may add valuable information to current tumor staging. Serum mSEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.

Keywords: Methylated septin 9, Methylated, Colorectal cancer, Diagnosis, Prognosis

Core tip: This study retrospectively explored the value of serum septin 9 methylation (mSEPT9) in the diagnosis and prognosis of colorectal cancer in a Chinese population. Preoperative mSEPT9 levels in 354 enrolled patients were retrospectively analyzed. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 colorectal cancer cases from The Cancer Genome Atlas database were evaluated using bioinformatics analyses. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies.