SCTR hypermethylation is a diagnostic biomarker in colorectal cancer

Abstract

Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of the secretin receptor (SCTR) gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA) CRC methylation data (N = 440), and verified in a large‐scale test set (N = 938) from the Gene Expression Omnibus (GEO). Targeted bisulfite sequencing analysis was developed and applied to detect the methylation status of SCTR in our independent validation set (N = 374). Our findings revealed that the SCTR gene was frequently hypermethylated at its CpG islands in CRC. In the TCGA discovery set, the diagnostic score was constructed using 4 CpG sites (cg01013590, cg20505223, cg07176264, and cg26009192) and achieved high diagnostic performance (area under the ROC curve [AUC] = 0.964). In the GEO test set, the diagnostic score had robust diagnostic ability to distinguish CRC (AUC = 0.948) and its precursor lesions (AUC = 0.954) from normal samples. Moreover, hypermethylation of the SCTR gene was also found in cell‐free DNA samples collected from CRC patients, but not in those from healthy controls. In the validation set, consistent results were observed using the targeted bisulfite sequencing array. Our study highlights that hypermethylation at CpG islands of the SCTR gene is a potential diagnostic biomarker in CRCs and its precursor lesions.

Secretin Receptor as a Target in Gastrointestinal Cancer: Expression Analysis and Ligand Development

“…This contrasts with the literature on GPCR overexpression in other tumors, such as neuroendocrine neoplasms, where overexpression of somatostatin receptors and the receptor for gastric inhibitory polypeptide may be variable or reduced in G3 tumors in contrast to G1 and G2 tumors [73,74]. In colorectal carcinoma (CRC), a massive methylation of the SCTR gene with lower methylation levels in precancerous lesions (polyp, adenoma) and highest levels in carcinoma has recently been reported [75]. Consequently, and in contrast to the findings in this study for PDAC and esophageal cancer, SCTR expression in CRC may be strongly reduced rather than upregulated.…”

Dynamic liquid biopsy components as predictive and prognostic biomarkers in colorectal cancer

“…On the other hand, several markers such as MutL homolog 1(MLH1) promoter methylation markers [ 136 ] and Septin 9 (SEPT 9) [ 137 ] have also been identified as suitable markers with high sensitivities (78% and 87%) and specificities (100% to 90.6%) to differentiate CRC patients from heathy controls. In addition to this, two separate studies have documented that Secretin Receptor (SCTR) hypermethylation and Transmembrane Protein 240 (TMEM240) promoter hypermethylation is detected only in cfDNA samples of CRC patients but not in healthy controls [ 138 ]. For e.g.…”

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

“…Hence, an increased survival rate can be reached by early diagnosis and prompt action. Recent studies focused on potential biomarkers that can be used in medical practice for the early detection of CRC, which may include the above-mentioned genes or others such as UNC5D, KCNA1 [ 106 ], FMN2 [ 107 ], JAM3 [ 108 ], GSDME [ 109 ], CRF [ 110 ], SMAD3 [ 111 ], SCTR [ 112 ], CNRIP1 [ 113 ], NEUROG1 [ 114 ], and p16 [ 115 ].…”