研究动态
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通过生物信息学分析和细胞实验研究 GPR143 作为皮肤黑色素瘤进展的有前途的新型标记物。

Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.

发表日期:2023 Nov 09
作者: Ruimin Bai, Pan Yin, Zixuan Xing, Shaobo Wu, Wen Zhang, Xinyu Ma, Xinyi Gan, Yuxia Liang, Qijuan Zang, Hao Lei, Yi Wei, Chaonan Zhang, Bingling Dai, Yan Zheng
来源: GENES & DEVELOPMENT

摘要:

皮肤黑色素瘤(SKCM)是一种侵袭性且危及生命的皮肤癌。 G蛋白偶联受体143(GPR143)属于G蛋白偶联受体超家族。我们使用TCGA、GTEx、CCLE和Human Protein Atlas数据库检测GPR143的mRNA和蛋白表达。此外,我们还进行了生存分析,并使用受试者工作特征(ROC)曲线评估了诊断效果。通过CIBERSORT、R编程、TIMER、基因表达谱交互分析、Sangerbox和Kaplan-Meier绘图仪数据库分析,我们探讨了GPR143、免疫浸润和免疫浸润细胞的基因标记表达之间的关系。此外,我们使用 R 编程和数据库(包括 STRING、GeneMANIA 和 GSEA)研究了可能与 GPR143 相互作用的蛋白质及其功能。同时,使用cBioPortal、UALCNA和MethSurv数据库检查SKCM中GPR143的基因组改变和甲基化。 Connectivity Map 数据库用于发现针对 SKCM 的潜在有效治疗分子。最后,我们进行了细胞实验来研究GPR143在SKCM中的潜在作用。我们证明与正常组织相比,GPR143在SKCM中的表达水平显着高。 GPR143 高表达和 GPR143 低甲基化状态与较差的预后相关。 ROC分析显示GPR143的诊断效能为0.900。此外,GPR143 表达与 SKCM 中的免疫浸润显着相关。我们鉴定了20个邻近基因,它们富集的途径是色素沉着的合成代谢过程、免疫调节等。基因组改变分析揭示了 SKCM 中与 GPR143 表达相关的显着不同的拷贝数变异,浅缺失可能导致 GPR143 高表达。确定了十种针对 SKCM 的潜在治疗药物。 GPR143 敲低可抑制黑色素瘤细胞增殖、迁移和集落形成,同时促进细胞凋亡。我们的研究结果表明,GPR143 可作为一种新型诊断和预后生物标志物,并与 SKCM 的进展相关。© 2023。作者,拥有独家许可施普林格科学商业媒体有限责任公司(施普林格自然的一部分)。
Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors.We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM.We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis.Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.