Glypican 6 is a putative biomarker for metastatic progression of cutaneous melanoma

• Published in: PloS one Vol. 14; no. 6; p. e0218067
• Main Authors: Li, Yuanyuan, Li, Melissa, Shats, Igor, Krahn, Juno M, Flake, Gordon P, Umbach, David M, Li, Xiaoling, Li, Leping
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.06.2019; Public Library of Science (PLoS)
• Subjects: Biochemistry; Biological markers; Biology; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Bone growth; Bone morphogenetic proteins; Breast cancer; Cancer; Cancer genetics; Cancer metastasis; Care and treatment; Cell adhesion; Cell Line, Tumor; Cell migration; Comparative analysis; Environmental health; Female; Fibroblast growth factors; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genomes; Genomics; Glypicans - biosynthesis; Glypicans - genetics; Growth factors; Health sciences; Heparan sulfate; Heparan sulfate proteoglycans; Humans; Laboratories; Li, Melissa; Liver cancer; Lymphatic system; Male; Medical research; Medicine and Health Sciences; Melanocytes; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Melanoma, Cutaneous Malignant; Metastases; Metastasis; MicroRNAs - biosynthesis; MicroRNAs - genetics; Neoplasm Metastasis; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Ovarian cancer; Prognosis; Proteins; Research and Analysis Methods; Ribonucleic acid; RNA; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Signal transduction; Skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumor cell lines; Tumor suppressor genes; Tumors; Up-Regulation; Vemurafenib; Wnt protein; North Carolina; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0218067

Due to the poor prognosis of advanced metastatic melanoma, it is crucial to find early biomarkers that help identify which melanomas will metastasize. By comparing the gene expression data from primary and cutaneous melanoma samples from The Cancer Genome Atlas (TCGA), we identified GPC6 among a set of genes whose expression levels can distinguish between primary melanoma and regional cutaneous/subcutaneous metastases. Glypicans are thought to play a role in tumor growth by regulating the signaling pathways of Wnt, Hedgehogs, fibroblast growth factors (FGFs), and bone morphogenetic proteins (BMPs). We showed that GPC6 expression was up-regulated in a melanoma cell line compared to normal melanocytes and in metastatic melanoma compared to primary melanoma. Furthermore, GPC6 expression was positively correlated with genes largely involved in cell adhesion and migration in both melanoma samples and in RNA-seq samples from other TCGA tumors. Our results suggest that GPC6 may play a role in tumor metastatic progression. In TCGA melanoma samples, we also showed that GPC6 expression was negatively correlated with miR-509-3p, which has previously been shown to function as a tumor suppressor in various cancer cell lines. We overexpressed miR-509-3p in A375 melanoma cells and showed that GPC6 expression was significantly suppressed. This result suggested that GPC6 was a putative target of miR-509-3p in melanoma. Together, our findings identified GPC6 as an early biomarker for melanoma metastatic progression, one that can be regulated by miR-509-3p.