Identification of IL10RA by Weighted Correlation Network Analysis and in vitro Validation of Its Association With Prognosis of Metastatic Melanoma.
Identification of IL10RA by Weighted Correlation Network Analysis and in vitro Validation of Its Association With Prognosis of Metastatic Melanoma.
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通过加权相关网络分析鉴定 IL10RA 并体外验证其与转移性黑色素瘤预后的关系
DOI：
10.3389/fcell.2020.630790
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发表时间：
2020
影响因子：
5.5
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Cheng S;Li Z;Zhang W;Sun Z;Fan Z;Luo J;Liu H
皮肤黑色素瘤（SKCM）是皮肤癌患者的主要死亡原因，其高转移常导致恶性黑色素瘤患者预后不良。然而，转移性黑色素瘤的分子机制仍有待阐明。在这项研究中，我们的目的是确定和验证与转移性黑色素瘤相关的预后生物标志物。我们首先利用GEO的大规模公共基因表达谱构建了共表达网络，并使用加权基因共表达网络分析（WGCNA）从中筛选出候选基因。通过平均连锁层次聚类共建立了8个模块，并从具有临床意义的模块中鉴定出111个枢纽基因。接下来，使用来自GEO和TCGA的另外两个数据集进一步筛选与转移性黑色素瘤预后相关的生物标志物基因，并通过生存分析确定了11个关键基因。我们发现，IL10RA与所有鉴定的生物标志物基因中的临床重要模块具有最高的相关性。进一步的体外生物化学实验，包括CCK 8测定、伤口愈合测定和transwell测定，已经证实IL 10RA可以显著抑制黑素瘤细胞的增殖、迁移和侵袭。此外，基因集富集分析显示PI3K-AKT信号通路在具有高表达IL 10RA的转移性黑素瘤中显著富集，表明IL 10RA通过PI3K-AKT通路介导转移性黑素瘤。
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.
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P-Rex1 是有效的成黑细胞迁移和黑色素瘤转移所必需的。
影响因子：
16.6
作者：
通讯作者：
--
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
4.4
作者：
Li, Qingsheng;Anderson, Charles D.;Egilmez, Nejat K.
通讯作者：
Egilmez, Nejat K.
影响因子：
4.6
作者：
Klatt W;Wallner S;Brochhausen C;Stolwijk JA;Schreml S
通讯作者：
Schreml S
影响因子：
45.3
作者：
Balch, Charles M.;Gershenwald, Jeffrey E.;Sondak, Vernon K.
通讯作者：
Sondak, Vernon K.