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

• DOI: 10.1371/journal.pone.0218067
• Publication Date: 2019-06-14T17:37:28Z
• Authors: Yuanyuan Li; Melissa Li; Igor Shats; Juno M. Krahn; Gordon P. Flake; David M. Umbach; Xiaoling Li; Leping Li
• Keywords: Male; 0301 basic medicine; Skin Neoplasms; Science; Q; R; Neoplasm Proteins; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Melanoma, Cutaneous Malignant; Glypicans; Cell Line, Tumor; Biomarkers, Tumor; Medicine; Humans; Female; RNA, Neoplasm; Neoplasm Metastasis; Melanoma; Research Article

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.