DOI: 10.1200/go-26-45000 ISSN: 2687-8941

Preliminary Evaluation of SDC2 as a Minimally Invasive Cell-Free DNA—based Epigenetic Biomarker for Early Detection of Colorectal Cancer Among a Sri Lankan Cohort

Thinuri Indrapala, Jayamal Ariyaratne, Gayani Galhena
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PURPOSE

Current colorectal cancer (CRC) screening methods, including colonoscopy and faecal occult blood tests (FOBT) suffer from low patient compliance. Since early detection is the most effective strategy for improving CRC prognosis, non-invasive screening tools with high sensitivity and specificity are an urgent requirement. Methylated SDC2 has demonstrated promise as a CRC biomarker in populations outside South Asia; however, its validation within South Asian populations remains unexplored. Given the population-specific nature of DNA methylation patterns, this study aimed to evaluate SDC2 methylation as a non-invasive, blood-based biomarker for CRC detection in the Sri Lankan population, representing, to our knowledge, the first study of its kind in this setting.

METHODS

A nested quantitative methylation-specific PCR (qMSP) assay was performed on plasma cell-free DNA from 28 treatment-naive CRC cases and 28 age and sex matched cancer-free controls recruited from Apeksha Hospital, Sri Lanka. The percent methylated reference (PMR) relative to the internal control gene ACTB was calculated for each sample. Diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis.

RESULTS

Patients with a confirmed diagnosis of CRC (Stage I-II: 70%, Stage III-IV: 30%, median age 62.7 years, 17% male) were recruited. A statistically significant difference in PMR values was observed between CRC cases and cancer-free controls (Mann-Whitney U test, P = .003). ROC curve analysis revealed a sensitivity of 100% and specificity of 39.3% at a cut-off PMR of 0.002 (AUC = 0.732). The high sensitivity indicates strong potential for screening applications, despite the limited specificity that may result in false positives requiring follow-up testing. The performance, however, is comparable to previously reported values for SEPT9 methylation (AUC ≈ 0.71), while higher discriminatory performance has been reported for multi-marker panels (AUC > 0.9). SDC2 methylation detected in plasma can serve as a viable non-invasive epigenetic biomarker for CRC screening for the Sri Lankan population.

CONCLUSION

Further studies in larger cohorts and employment of a multi-marker panel are warranted to optimise specificity and support translation into the clinical arena.

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