Evaluating the Clinical Performance of SDC2/NDRG4 Methylation for Colorectal Cancer Detection

Abstract

Purpose: The performance and clinical accuracy of combined SDC2/NDRG4 methylation were evaluated in diagnosing colorectal cancer (CRC) and advanced adenoma. Methods: A total of 2333 participants were enrolled to assess the sensitivity and specificity of biomarkers in diagnosing CRC in a multicenter clinical trial through feces DNA methylation tests. Results: SDC2/NDRG4 methylation showed excellent performance for CRC detection in biomarker research and the real world. Its sensitivity for detecting CRC, early CRC and advanced adenoma were 92.06%, 91.45% and 62.61%, respectively. Its specificity was 94.29%, with a total coincidence rate of 88.28%. When interference samples were included, the specificity was still good (82.61%). Therefore, the SDC2/NDRG4 methylation test showed excellent performance in detecting CRC and advanced adenoma under clinical application.

Plain language summary

Colorectal cancer (CRC) is one of the most malignant tumors of the digestive system and second only to breast cancer and lung cancer in terms of global incidence. Early CRCs are challenging to determine given their atypical nature. In contrast, late CRC symptoms are affected by the type, location and range of the lesion and complications. Therefore, CRC patients are generally diagnosed late, present with a high degree of malignancy, and have poor prognosis and 5-year survival rates. The current study therefore evaluated whether SDC2 and NDRG4 methylation could be used for diagnosis CRCs at an early stage and whether it has the potential to detect asymptomatic patients with adenomas. The findings presented herein will certainly help support the early diagnosis of CRC and precancerous lesions in clinical practice.

Tweetable abstract

SDC2/NDRG4 methylation showed excellent performance for CRC detection in a real-world setting. Its sensitivity for detecting CRC, early CRC and advanced adenoma were 92.06%, 91.45% and 62.61%, respectively. Its specificity was 94.29%, with a total coincidence rate of 88.28%.

Keywords::

• advanced adenoma
• colorectal cancer
• diagnosis
• multicenter clinical study
• SDC2/NDRG4 methylation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/epi-2023-0290

Author contributions

All authors contributed to the study conception and design. Z Ke, Q He, X Zhang, B Zhu, M Hu, L Chang and ZX BU performed experiments; Q Cao, A Qin, C Xiao and L Fu collected data (patient information and stool sample preparation); Z Ke, Q He, Q Cao, J Chuan, A Qin, L Tang and T Yang analyzed the data; Y Wang and W Liu designed the experiment. Z Ke, Q He, L Tang, Y Wang and W Liu take part in writing, reviewing and revising article. Y Wang and W Liu are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Financial disclosure

This work was supported by Project of the Natural Science Foundation of Hunan Province (grant no. 2021JJ40512). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

GeneTalks Biotech Co., Ltd and department of general surgery, Xiangya Hospital Central South University were jointly presiding the project in scientific research. All participating units declare that they have no commercial interests with each other. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Ethical conduct of research

All methods were carried out in accordance with relevant guidelines and regulations. Biomarker research approval was provided by the medical ethics committee of Xiangya Hospital of Central South University (reference no: 201712844). For the clinical study, a double-blind study involving three hospitals (Xiangya Hospital, Central South University, Hunan Cancer Hospital and Sir Run Run Shaw Hospital, Zhejiang University) was designed, which enrolled over 1000 participants according to the Technical Guidelines for Clinical Trials of in Vitro Diagnostic Reagents released in 2021 by the NMPA (reference no: GCP [2021010005], 2021-259, 20210420-8). Informed consent was obtained from all individual participants included in the study.

Writing assistance

The authors received English language editing services from ENAGO by Project (grant no. 2021JJ40512) .

Data sharing statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. The authors certify that this manuscript reports original clinical trial data. Deidentified, individual data that underlie the results reported in this article (text, tables, figures and appendices), along with the study protocol and statistical analysis plan, will be available will be available indefinitely for anyone who wants access to them. After 24 months following article publication, the data will be available in ResMan (http://www.medresman.org.cn/login.aspx).

Additional information

Funding

This work was supported by Project of the Natural Science Foundation of Hunan Province (grant no. 2021JJ40512). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.