Identification of IL10RA by Weighted Correlation Network Analysis and in vitro Validation of Its Association With Prognosis of Metastatic Melanoma
Autor: | Si Cheng, Zhe Li, Wenhao Zhang, Zhiqiang Sun, Zhigang Fan, Judong Luo, Hui Liu |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Candidate gene Biology Metastasis survival analysis Cell and Developmental Biology 03 medical and health sciences 0302 clinical medicine IL10RA medicine prognostic biomarker lcsh:QH301-705.5 Survival analysis Original Research skin cutaneous melanoma (SKCM) WGCNA Melanoma Weighted correlation network analysis Cell Biology medicine.disease 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis Cutaneous melanoma Cancer research Biomarker (medicine) Skin cancer Developmental Biology metastatic melanoma |
Zdroj: | Frontiers in Cell and Developmental Biology, Vol 8 (2021) Frontiers in Cell and Developmental Biology |
Popis: | Skin cutaneous melanoma (SKCM) is the major cause of death for skin cancer patients, its high metastasis often leads to poor prognosis of patients with malignant melanoma. However, the molecular mechanisms underlying metastatic melanoma remain to be elucidated. In this study we aim to identify and validate prognostic biomarkers associated with metastatic melanoma. We first construct a co-expression network using large-scale public gene expression profiles from GEO, from which candidate genes are screened out using weighted gene co-expression network analysis (WGCNA). A total of eight modules are established via the average linkage hierarchical clustering, and 111 hub genes are identified from the clinically significant modules. Next, two other datasets from GEO and TCGA are used for further screening of biomarker genes related to prognosis of metastatic melanoma, and identified 11 key genes via survival analysis. We find that IL10RA has the highest correlation with clinically important modules among all identified biomarker genes. Further in vitro biochemical experiments, including CCK8 assays, wound-healing assays and transwell assays, have verified that IL10RA can significantly inhibit the proliferation, migration and invasion of melanoma cells. Furthermore, gene set enrichment analysis shows that PI3K-AKT signaling pathway is significantly enriched in metastatic melanoma with highly expressed IL10RA, indicating that IL10RA mediates in metastatic melanoma via PI3K-AKT pathway. |
Databáze: | OpenAIRE |
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