Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 8:13:857308.
doi: 10.3389/fimmu.2022.857308. eCollection 2022.

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

Guoming Chen  1 , Dongqiang Luo  2 , Nan Zhong  2 , Danyun Li  2 , Jiyuan Zheng  2 , Hui Liao  2 , Zhuoyao Li  2 , Xiaoxiao Lin  2 , Qiqi Chen  2 , Cheng Zhang  1 , Yuanjun Lu  1 , Yau-Tuen Chan  1 , Qing Ren  1 , Ning Wang  1 , Yibin Feng  1
Affiliations

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

Guoming Chen et al. Front Immunol. .

Abstract

Background: Glypican 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.

Methods: By 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.

Results: The 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.

Conclusion: Through 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.

Keywords: GPC2; diagnosis; immunization; pan-cancer; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Differential expression of GPC2. (A) Expression of GPC2 in normal tissues. (B) Expression of GPC2 in cancer cell lines. (C) Expression of GPC2 in 33 types of cancer. (D) Comparison of GPC2 expression between tumor and paired normal samples. (E) Comparison of GPC2 expression between tumor and normal samples. *p < 0.05, **p < 0.01, ***p < 0.001. ns, not statistically significant.
Figure 2
Figure 2
The protein expression of GPC2 in immunohistochemical images of normal (left) and tumor (right) groups.
Figure 3
Figure 3
Association between GPC2 expression and tumor stage. *p < 0.05, **p < 0.01, ***p < 0.001. ns, not statistically significant.
Figure 4
Figure 4
AUC of ROC curves verified the diagnosis performance of GPC2 in the TCGA cohort.
Figure 5
Figure 5
Association between GPC2 expression and overall survival (OS). (A) Forest plot of OS associations in 33 types of tumor. (B–S) Kaplan–Meier analysis of the association between GPC2 expression and OS.
Figure 6
Figure 6
Association between GPC2 expression levels and disease-specific survival (DSS). (A) Forest plot of association of GPC2 expression and DSS in 33 types of tumor. (B–O) Kaplan–Meier analysis of the association between GPC2 expression and DSS.
Figure 7
Figure 7
Association between GPC2 expression levels and progression-free interval (PFI). (A) Forest plot of PFI association with GPC2 expression in 33 tumor types. (B–S) Kaplan–Meier analysis of the association between GPC2 expression and PFI.
Figure 8
Figure 8
Relationship between GPC2 expression and immune cell infiltration in different cancers. *p < 0.05, **p < 0.01.
Figure 9
Figure 9
Co-expression of GPC2 and immune-related genes. *p < 0.05, **p < 0.01.
Figure 10
Figure 10
The promoter methylation level of GPC2 in cancers.
Figure 11
Figure 11
Mutation of GPC2. (A) Alteration frequency of GPC2. (B) OncoPrint visual summary of alterations in a query of GPC2 from cBioPortal.
Figure 12
Figure 12
ceRNA networks of GPC2 (red circle represents the hub gene, yellow vs. represent the miRNAs, green hexagons represent the lncRNAs, and purple hexagons represent the circRNAs).
Figure 13
Figure 13
The gene–gene interaction network of GPC2 from GeneMANIA.
See this image and copyright information in PMC

References

    1. Iskandar AC, Rochmawati E, Wiechula R. Patient′s Experiences of Suffering Across the Cancer Trajectory: A Qualitative Systematic Review Protocol. J Adv Nurs (2021) 77(2):1037–42. doi: 10.1111/jan.14628 - DOI - PubMed
    1. Singh AK, McGuirk JP. CAR T Cells: Continuation in a Revolution of Immunotherapy. Lancet Oncol (2020) 21(3):e168–78. doi: 10.1016/S1470-2045(19)30823-X - DOI - PubMed
    1. Kennedy LB, Salama AKS. A Review of Cancer Immunotherapy Toxicity. CA Cancer J Clin (2020) 70(2):86–104. doi: 10.3322/caac.21596 - DOI - PubMed
    1. Yiping Y. Cancer Immunotherapy: Harnessing the Immune System to Battle Cancer. J Clin Invest (2015) 125(9):3335–7. doi: 10.1172/JCI83871 - DOI - PMC - PubMed
    1. Srivastava S, Hanash S. Pan-Cancer Early Detection: Hype or Hope? Cancer Cell (2020) 38(1):23–4. doi: 10.1016/j.ccell.2020.05.021 - DOI - PubMed

Publication types