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. 2024 Jul 30;24(1):916.
doi: 10.1186/s12885-024-12645-4.

A novel dual-target Septin9 methylation assay for improved detection of early-stage colorectal cancer and high-grade intraepithelial neoplasia

Youming Wu #  1 , Yongqing Tong #  2 , Haitao Zhang #  3 , Yun Li  3 , Xu Zhu  2 , Ming Li  2 , Lili Qiu  4 , Wenlan Liu  3 , Siqing Mei  2 , Yu Mao  5 , Yanhua Cao  5 , Caiyan Su  5 , Wentao Yu  5 , Junli Wang  6 , Taizhong Wang  6 , Zhongyuan Zhu  7 , De-Hua Yu  8   9
Affiliations

A novel dual-target Septin9 methylation assay for improved detection of early-stage colorectal cancer and high-grade intraepithelial neoplasia

Youming Wu et al. BMC Cancer. .

Abstract

Background: Colorectal cancer (CRC) ranks as the third most common malignancies in the world, and periodic examination of the patient is advantageous in reducing the mortality of CRC. The first blood-based Septin9 gene methylation assay which recognized by the US FDA for CRC examination was Epi proColon. However, this assay was not broadly applied in the current clinical guideline because of its relatively lower sensitivity in the detection of early-stage CRC.

Methods: This study aimed at developing a new multiplex Septin9 methylation assay (ColonUSK) which simultaneously evaluates two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. ColonUSK proved increased sensitivity, with a detection limit as low as 12pg of the positive DNA compared with the Septin9 assay targeting one CpG-rich subregion. 1366 subjects were prospectively recruited from four comprehensive hospitals in China in an opportunistic screening study for assessing its value in CRC detection. Blind testing was developed to evaluate ColonUSK in comparison with clinical examination using clinical gold standard such as colonoscopy.

Results: The assay demonstrates clinical sensitivity for diagnosing colorectal cancer (CRC) and advanced adenoma at rates of 77.34% and 25.26%, respectively. Furthermore, ColonUSK exhibits a high degree of specificity for non-CRC cases (95.95%) clinically. Significantly, the detection rate of cases in high-grade intraepithelial neoplasia increased to 54.29%. The value for the assay in the Kappa test was 0.76, showing a high degree of consistency between ColonUSK and clinical gold standard.

Conclusions: ColonUSK indicated moderate diagnostic value and could become a non-invasive detection way for CRC. The implementation of the ColonUSK assay has the capacity to markedly enhance CRC screening practices.

Keywords: Colorectal cancer (CRC); CpG-rich subregions; Methylation; PCR; Septin9.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Clinical characteristics of patients and controls
Fig. 2
Fig. 2
ROC curve for the opportunistic screening trial
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