Promoter methylation of matrix metallopeptidase 9 in peripheral blood mononuclear cells: A novel biomarker in a promising source for noninvasive colorectal cancer diagnosis
Alireza Shaygannejad1, Behnoush Sohrabi2, Shima Rahimi Rad3, Farzaneh Yousefisadr4, Hossein Darvish5, Mohsen Soosanabadi6
1 Department of Internal Medicine, Division of Gastrointestinal, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
2 Department of Biology, Faculty of Sciences, Arak University, Arak; Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
3 Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
5 Neuroscience Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
6 Department of Medical Genetics, Semnan University of Medical Sciences, Semnan, Iran
Department of Medical Genetics, Semnan University of Medical Sciences, Semnan
Source of Support: None, Conflict of Interest: None
Objectives: Colorectal cancer (CRC) has been described as a “silent disease,” which can be readily treated in most patients when discovered in its early stages. Considering the limitations of the current conventional tests for the diagnosis of CRC, researchers strive to find noninvasive and more valid biomarkers for the early detection of CRC. It has been shown that tumor-specific methylation patterns can also be identified in peripheral blood mononuclear cells (PBMCs) and are reliable sources of methylation analysis for CRC screening.
Materials and Methods: We carried out a quantitative methylation analysis on matrix metallopeptidase 9 (MMP9) promoter using methylation quantification endonuclease-resistant DNA (MethyQESD) method. A total of 70 patients with CRC and 70 normal controls were enrolled in this study for methylation analysis in the PBMCs.
Results: Our findings discovered a considerable hypermethylation of MMP9 promoter in CRC patients compared with healthy controls (mean: 47.30% and 20.31%, respectively; P > 0.001). The sensitivity and specificity of the MMP9 gene for the diagnosis of CRC were 88% and 78%, respectively. In addition, on the basis of area under the curve values, the diagnostic power of the MMP9 gene was 0.976 (P < 0.001). Moreover, our analysis established that MMP9 methylation was significantly different between the different stages of CRC (P: 0.034).
Conclusions: Our results showed that MMP9 promoter methylation in PBMCs can be used as an outstanding biomarker for CRC diagnosis. Besides, we confirmed that PBMCs are reliable sources of methylation analysis for CRC screening and MethyQESD is an accurate and fast method for quantitative methylation analyses.