Dataset Information

The Expression, Regulation, and Biomarker Potential of Glypican-1 in Cancer.

ABSTRACT: Glypican-1 (GPC-1) and other glypicans are a family of heparan sulfate proteoglycans. These proteins are highly expressed on the cell membrane and in the extracellular matrix, functioning mainly as modulators of growth factor signaling. Some of them are abnormally expressed in cancer, possibly involved in tumorigenesis, and detectable in blood as potential clinical biomarkers. GPC-1 is another glypican member that has been found to be associated with some cancers, and has increasingly interested the cancer field. Here we provide a brief review about GPC-1 in its expression, signaling and potential as a cancer biomarker.

SUBMITTER: Wang S

PROVIDER: S-EPMC6640540 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

The Expression, Regulation, and Biomarker Potential of Glypican-1 in Cancer.

Wang Sen S Qiu Yudong Y Bai Bing B

Frontiers in oncology 20190712

Glypican-1 (GPC-1) and other glypicans are a family of heparan sulfate proteoglycans. These proteins are highly expressed on the cell membrane and in the extracellular matrix, functioning mainly as modulators of growth factor signaling. Some of them are abnormally expressed in cancer, possibly involved in tumorigenesis, and detectable in blood as potential clinical biomarkers. GPC-1 is another glypican member that has been found to be associated with some cancers, and has increasingly interested ...[more]

PMID: 31355137

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Project description:PD-1/PD-L1 immune checkpoint inhibitors show potential for cervical cancer treatment. However, low response rates suggest that patient selection based on PD-L1 protein expression is not optimal. Here, we evaluated different PD-L1 detection methods and studied transcriptional regulation of PD-L1/PD-L2 expression by The Cancer Genome Atlas (TCGA) mRNAseq analysis. First, we determined the copy number of the PD-L1/PD-L2 locus by fluorescence in situ hybridization (FISH), PD-L1 mRNA expression by RNA in situ hybridization (RNAish), and PD-L1/PD-L2 protein expression by immunohistochemistry (IHC) on tissue microarrays containing a cohort of 60 patients. Additionally, distribution of PD-L1/PD-L2 was visualized based on flow cytometry analysis of single-cell suspensions (n = 10). PD-L1/PD-L2 locus amplification was rare (2%). PD-L1 mRNA expression in tumor cells was detected in 56% of cases, while 41% expressed PD-L1 protein. Discordant scores for PD-L1 protein expression on tumor cells between cores from one patient were observed in 27% of cases. Interestingly, with RNAish, PD-L1 heterogeneity was observed in only 11% of the cases. PD-L2 protein expression was found in 53%. PD-L1 mRNA and protein expression on tumor cells were strongly correlated (p < 0.001). PD-L1 and PD-L2 protein expression showed no correlation on tumor cells (p = 0.837), but a strong correlation on cells in stromal fields (p < 0.001). Co-expression of PD-L1 and PD-L2 on macrophage-like populations was also observed with flow cytometry analysis. Both PD-L1 and PD-L2 TCGA transcript levels strongly correlated in the TCGA data, and both PD-L1 and PD-L2 strongly correlated with interferon gamma (IFNG) expression/transcript levels (p < 0.0001). Importantly, patients with high PD-L1/PD-L2/IFNG transcript levels had a survival advantage over patients with high PD-L1/PD-L2 and low IFNG expression. Based on these findings, we conclude that PD-L1/PD-L2 expression in cervical cancer is mainly associated with interferon induction and not gene amplification, which makes FISH unsuitable as biomarker. The heterogeneous PD-L1 and PD-L2 expression patterns suggest IHC unreliable for patient selection. RNAish, in conjunction with interferon signaling evaluation, seems a promising technique for immune checkpoint detection. These results warrant further investigation into their prognostic and predictive potential.

Dataset Information

The Expression, Regulation, and Biomarker Potential of Glypican-1 in Cancer.

Publications

The Expression, Regulation, and Biomarker Potential of Glypican-1 in Cancer.

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