Colorectal cancer is a frequent malignant tumor with the third-highest incidence rate and the fourth-highest mortality rate globally [1], [2]. With the development of pathophysiological researche, various treatment methods for colorectal cancer, including surgical resection, radiotherapy, extensive surgery, targeted therapy, immunotherapy, and individualized therapy, have shown considerable feasibility and value [3]. Because pharmacogenomics is not widely used in colorectal cancer detection, and the incidence of acquired drug resistance is increasing, the overall survival rate of patients remains poor [3], [4], [5]. Therefore, it is still important to investigate novel biomarkers and targets to improve the diagnostic rate and prognosis of colorectal cancer.

Glypicans are a class of glycosylphosphatidylinositol (GPI)-anchored, cell surface glycoproteins that involve in multiple biological processes, including controlling cell growth, death and differentiation [6]. Glypican 2 (GPC2), a member of the glypican gene family, is expressed in multiple kinds of cancer. For example, the high expression of GPC2 in neuroblastoma cases promoted Wnt/β-catenin signaling and enhanced the N-Myc expression to drive neuroblastoma tumorigenesis [7]. Another group has confirmed the oncogene-like function of GPC2 in neuroblastoma. Meanwhile, they reported lay firm groundwork for the development of GPC2 directed immune-based therapies, including not only anti-GPC2 ADCs but also CAR T cells directed towards GPC2 [8]. A recent study has investigated that GPC2 was highly expressed in glioblastoma and associated with the regulation of the oxidative phosphorylation process, which was benefit for the prognosis and therapy of glioblastoma [9]. Similarly, by the analysis of the data from The Cancer Genome Atlas (TCGA) database, Tao et al. found that high expression of GPC2 was highly related to the poor prognosis of patients with pancreatic ductal adenocarcinoma by multiple pathways, such as DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA) [10]. However, its expression pattern, functional role and mechanism in colorectal cancer remain unclear.

In this study, we analyzed the expression and clinical data from TCGA and found that GPC2 was overexpressed in colon cancer patients. Functionally, we identified that the downregulation of GPC2 suppressed tumor cell proliferation both in vitro and in vivo. Moreover, downregulation of GPC2 inhibited the expression of CEP164 expression, which might further induce G2/M-phase arrest. This is the first time that we demonstrated GPC2 served as a diagnostic and prognostic biomarker for colorectal cancer.