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鉴定 CXCL13 作为一种与皮肤黑色素瘤患者肿瘤发生和预后相关的免疫相关生物标志物。

Identification of CXCL13 as an Immune-Related Biomarker Associated with Tumorigenesis and Prognosis in Cutaneous Melanoma Patients.

机构信息

Department of Orthopedics, The Affiliated Yuebei People's Hospital of Shantou University Medical College, Shaoguan, Guangdong, China (mainland).

出版信息

Med Sci Monit. 2021 Jul 11;27:e932052. doi: 10.12659/MSM.932052.

DOI:10.12659/MSM.932052
PMID:34247183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8280950/
Abstract

BACKGROUND Melanoma is one of the most lethal tumors and its treatment is still challenging. It is urgent to detect novel therapy targets in melanoma. MATERIAL AND METHODS The GEO dataset was used to obtain a list of DEGS (differentially-expressed genes). Integrative bioinformatics analyses, including HPRD database, TCGA data, and TIMER, were performed to determine the role of CXCL13 in SKCM (skin cutaneous melanoma) progression and the immune environment. Furthermore, Pearson correlation coefficient analysis was used to measure correlations between CXCL13 and its co-expressed genes. Survival analysis, GO, and KEGG enrichment analysis were performed to investigate the role of CXCL13 in SKCM. RESULTS A total of 41 DEGs were identified in 3 GEO datasets, and 4 out of 41 DEGs are hub genes. Among the 4 hub genes, CXCL13 is involved in the most KEGG terms. CXCL13 is co-expressed with well-known immune checkpoint blockade targets, and it was associated with better overall survival. In addition, CXCL13 levels in infiltrating immune cells (neutrophil and myeloid dendritic cells) affect prognosis and survival in SKCM. Functional enrichment analysis clarified that CXCL13-co-expressed top 30 genes were associated with immune signaling pathways. Network analysis identified CXCL13 as a hub gene that interacts with CXCR5 to participate in immune-related biological process. CONCLUSIONS This study found that CXCL13 is associated with SKCM tumorigenesis and prognosis and immune infiltrations. Our result suggests that CXCL13 has great potential in development of novel immunotherapy targets in melanoma.

摘要

背景

黑色素瘤是最致命的肿瘤之一,其治疗仍然具有挑战性。迫切需要在黑色素瘤中发现新的治疗靶点。

材料和方法

使用 GEO 数据集获取 DEGS(差异表达基因)列表。进行综合生物信息学分析,包括 HPRD 数据库、TCGA 数据和 TIMER,以确定 CXCL13 在 SKCM(皮肤黑色素瘤)进展和免疫环境中的作用。此外,使用 Pearson 相关系数分析来测量 CXCL13 与其共表达基因之间的相关性。进行生存分析、GO 和 KEGG 富集分析,以研究 CXCL13 在 SKCM 中的作用。

结果

在 3 个 GEO 数据集中共鉴定出 41 个 DEG,其中 41 个 DEG 中有 4 个是枢纽基因。在这 4 个枢纽基因中,CXCL13 涉及最多的 KEGG 术语。CXCL13 与著名的免疫检查点阻断靶点共表达,与更好的总生存期相关。此外,浸润免疫细胞(中性粒细胞和髓样树突状细胞)中的 CXCL13 水平影响 SKCM 的预后和生存。功能富集分析表明,CXCL13 共表达的前 30 个基因与免疫信号通路有关。网络分析确定 CXCL13 是与 CXCR5 相互作用参与免疫相关生物过程的枢纽基因。

结论

本研究发现 CXCL13 与 SKCM 的肿瘤发生和预后以及免疫浸润有关。我们的结果表明,CXCL13 在开发黑色素瘤的新型免疫治疗靶点方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/ad045183ce72/medscimonit-27-e932052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/9a5525da7550/medscimonit-27-e932052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/82449e634800/medscimonit-27-e932052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/80bb29f5fe0a/medscimonit-27-e932052-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/e0307e66688b/medscimonit-27-e932052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/ad045183ce72/medscimonit-27-e932052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/9a5525da7550/medscimonit-27-e932052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/82449e634800/medscimonit-27-e932052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/80bb29f5fe0a/medscimonit-27-e932052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/01b3732dd531/medscimonit-27-e932052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/e0307e66688b/medscimonit-27-e932052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d094/8280950/ad045183ce72/medscimonit-27-e932052-g006.jpg

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Targeted Therapy in Melanoma and Mechanisms of Resistance.
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Promising prognostic value of Transglutaminase type 2 and its correlation with tumor-infiltrating immune cells in skin cutaneous melanoma.组织转谷氨酰胺酶2在皮肤黑色素瘤中的预后价值及其与肿瘤浸润免疫细胞的相关性
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