近年来，结直肠癌（CRC）的发病率有所上升。准确肿瘤标记物的识别已成为CRC研究的焦点。癌症往往出现早期和频繁的DNA甲基化。因此，识别准确的甲基化生物标记物将会提高CRC治疗的有效性。神经球蛋白（NGB）涉及神经和肿瘤性疾病。但是，目前没有关于NGB在CRC中表观遗传调控参与的报告。在大多数CRC组织和细胞系中，NGB被下调或沉默。在肿瘤组织中检测到NGB的高甲基化，但在正常组织中不存在或甲基化频率很低。NGB的过表达引起了G2/M期阻滞和细胞凋亡，在体外抑制了增殖、迁移、侵袭，并在体内抑制了CRC肿瘤生长和血管生成。基于同量同位素标记的相对和绝对定量（Itraq）蛋白质组学鉴定了大约40％与细胞-细胞黏附、侵袭和肿瘤血管形成有关的蛋白质，并证明GPR35对NGB调节的CRC肿瘤血管生成抑制至关重要。NGB是一种表观遗传沉默因子，在CRC中通过GPR35抑制转移。它有望成长为潜在的癌症风险评估因子和CRC早期诊断和预后评估的有价值的生物标志物。 ©2023.作者

The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC.NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell-cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC.NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.© 2023. The Author(s).