5-Methylcytosine (m5C) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis
Haofan Yin, Zhijian Huang, Shiqiong Niu, Liang Ming, Hong-Bo Jiang, Liang Gu, Weibin Huang, Jinye Xie, Yulong He, Changhua Zhang
Abstract
Current non-invasive tumor biomarkers failed to accurately identify patients with colorectal cancer (CRC), delaying CRC diagnosis and thus leading to poor prognosis. Dysregulation of 5-Methylcytosine (m 5 C) RNA has gradually been reported in various cancers, but their role in tumor diagnosis is rarely mentioned. Our study aimed to determine the role of m 5 C methylation modification in blood immune cells for the diagnosis of CRC. Peripheral blood samples were obtained from a total of 83 healthy controls and 196 CRC patients. We observed that m 5 C RNA contents in blood immune cells of CRC patients were markedly enhanced in both training set and validation set. Moreover, levels of m 5 C increased with CRC progression and metastasis but reduced after treatment. Compared with common blood tumor biomarkers, m 5 C levels in peripheral blood immune cells had superior discrimination and reclassification performance in diagnosing CRC. Besides, bioinformatics and qRT-PCR analysis identified increased expression of m 5 C-modified regulators NSUN5 and YBX1 in CRC patients’ blood. A series of animal models and cell co-culture models further demonstrated that CRC tumor cells could increase immune cells’ m 5 C levels and m 5 C-modified regulators. Monocyte was the predominant m 5 C-modified immune cell type in CRC patients’ blood by Gene set variation analysis (GSVA). Taken together, m 5 C methylation modification in peripheral blood immune cells was a promising biomarker for non-invasive diagnosis of CRC.