The Application Value of Syndecan-2 Gene Methylation for Colorectal Cancer Diagnosis: A Clinical Study and Meta-Analyses

Abstract

ObjectiveSyndecan-2 (SDC2) methylation has been previously reported as a sensitive biomarker for the early detection of colorectal cancer (CRC). Droplet digital PCR (ddPCR) is the latest development of PCR technology. It can accurately detect and quantify the target sequence of nucleic acid. ddPCR is widely used in research and clinical diagnosis. In the present study, we aimed to develop a ddPCR method to detect SDC2 gene methylation and evaluate the diagnostic value of SDC2 gene methylation.MethodsFirst, a ddPCR method was developed to measure SDC2 methylation in stool samples collected from 51 cases of normal, 23 cases of adenoma, and 86 cases of CRC. Subsequently, a meta-analysis of existing studies was conducted to judge the diagnostic value of SDC2 gene methylation in CRC. PUBMED, EMBASE, Web of Science, and Scopus databases were searched for relative studies. Meta-analysis was performed using Meta Disc 1.4 and STATA 15.0 software.ResultsThe ddPCR showed that the linearity, sensitivity, and specificity for the detection of SDC2 gene methylation could be down to 0.1% methylation level and 5 ng of methylated DNA input. In 109 cases of CRC, 107 cases could be detected, and the sensitivity was 98.17%. The median value of the percentage of methylated reference (PMR) in colorectal adenoma and CRC patients was significantly higher compared with the normal individuals (p < 0.001). In addition, we found that the PMR value was associated with the clinical staging of CRC. The difference of PMR in stage II and stage IIIA was statistically significant (p < 0.05). Moreover, the meta-analysis showed that 11 out of 87 studies were identified to report the feasibility of SDC2 gene methylation as a method to diagnose early CRC. The pooled sensitivity and specificity of SDC2 gene methylation test for CRC were 0.80 [95% CI (0.68–0.88)] and 0.93 [95% CI (0.91–0.94)], respectively. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 52.46 [95% CI (30.43–90.45)] and 0.94 [95% CI (0.92, 0.96)], respectively.ConclusionsThe ddPCR method was more sensitive and convenient to detect SDC2 gene methylation, and the pooled analysis showed that methylated SDC2 was a valuable biomarker for the non-invasive detection of CRC.

A Detailed meta Analysis on Diagnostic Value of SDC2 Methylation in Patients with Colorectal Carcinoma

“…In this study, we systematically searched published articles about the diagnostic value of SDC2 methylation in CRC patients and meta analysis was conducted to nd out the pooled DOR. Several meta analyses have been published on this topic (Yue et al 2022;). Compared to previous meta analyses, we searched articles in eight databases.…”

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

“…Furthermore, the United States Preventive Services Task Force initially recommended stool DNA testing as a screening approach for CRC in 2016[ 22 ]. In particular, syndecan-2 methylation (mSDC2) testing has emerged as a tool for early detection of CRC in stool and serum samples[ 23 , 24 ]. The SDC2 gene is a transmembrane heparan sulfate proteoglycan that is a member of the SDC proteoglycan family.…”

Combining methylated SDC2 test in stool DNA, fecal immunochemical test, and tumor markers improves early detection of colorectal neoplasms

“…The fecal immunochemical test (FIT) is non-invasive, simple, highly sensitive and is now widely used in the clinic. In recent years, fecal DNA testing has developed rapidly, and fecal DNA methylation testing has undergone numerous prospective clinical trials in China, confirming its suitability for CRC screening ( 11 – 13 ).Some studies have shown that the specificity of fecal SDC2 methylation (SDC2) was very high, or even > 90%, and had good diagnostic agreement with colonoscopy results, indicating that SDC2 is a suitable marker for CRC screening ( 11 , 14 – 16 ); however, the clinical application of SDC2 remains somewhat controversial ( 17 , 18 ). There have been few studies analyzing the relationships between clinicopathological features and SDC2 results.…”