GPC2 Is a Potential Diagnostic, Immunological, and Prognostic Biomarker in Pan-Cancer

Abstract

BackgroundGlypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction.MethodsBy comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes.ResultsThe results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers.ConclusionThrough pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.

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“…Total transcripts per million (TPM) expression profiles were obtained from the Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression (GTEx). 53 , 54 Log-normalized Stat3 and Fndc5 expression was qualified through Gencode V19 annotation. Stat3 and Fndc5 transcript values were analyzed with Pearson’s correlation tests across multiple cell lines and organs using R version 4.0.0 (R Foundation for Statistical Computing).…”

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Development of a basement membrane gene signature and identification of the potential candidate therapeutic targets for pancreatic cancer

“…The glycosylphosphatidylinositol anchor allows GPC, which is encoded by the glypican (GPC) family of genes, to bind to the cell membrane (23). A research showed GPC2 is a potential diagnostic, immunological, and prognostic biomarker (24). The importance of GPC2 in early detection, regulatory pathways, related genes, and chemicals has also been explored by researchers, who emphasized the extent to which it is expressed differently in cancer and healthy tissues (24).…”

“…A research showed GPC2 is a potential diagnostic, immunological, and prognostic biomarker (24). The importance of GPC2 in early detection, regulatory pathways, related genes, and chemicals has also been explored by researchers, who emphasized the extent to which it is expressed differently in cancer and healthy tissues (24). Pancreatic cancer prognostic prediction using GPC2 combined with GPC3 and GPC5 has shown great efficacy (25).…”