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ISG20 可作为一种潜在的生物标志物，并驱动肾透明细胞癌的肿瘤进展。

ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma.

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Aging (Albany NY). 2020 Jan 30;12(2):1808-1827. doi: 10.18632/aging.102714.

DOI:10.18632/aging.102714
PMID:32003757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7053611/
Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies and lacks reliable biomarkers for diagnosis and prognosis, which results in high incidence and mortality rates of ccRCC. In this study, ISG20, HJURP, and FOXM1 were identified as hub genes via weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Samples validation showed that only ISG20 was up-regulated in ccRCC. Therefore, ISG20 was selected for further study. High ISG20 expression was associated with poor overall survival and disease-free survival. Furthermore, the expression of ISG20 could effectively differentiate ccRCC from normal tissues and was positively correlated to clinical stages. Functional experiments proved that knockdown of ISG20 expression could obviously inhibit cell growth, migration, and invasion in ccRCC cells. To find the potential mechanisms of ISG20, gene set enrichment analysis (GSEA) was performed and revealed that high expression of ISG20 was significantly involved in metastasis and cell cycle pathways. In addition, we found that ISG20 could regulate the expression of MMP9 and CCND1. In conclusion, these findings suggested that ISG20 promoted cell proliferation and metastasis via regulating MMP9/CCND1 expression and might serve as a potential biomarker and therapeutic target in ccRCC.

摘要

透明细胞肾细胞癌（ccRCC）是最常见的恶性肿瘤之一，缺乏可靠的诊断和预后生物标志物，导致 ccRCC 的发病率和死亡率居高不下。本研究通过加权基因共表达网络分析（WGCNA）和 Cox 回归分析鉴定出 ISG20、HJURP 和 FOXM1 是 hub 基因。样本验证表明，ccRCC 中仅 ISG20 上调。因此，选择 ISG20 进行进一步研究。高 ISG20 表达与总生存期和无病生存期不良相关。此外，ISG20 的表达可有效区分 ccRCC 与正常组织，且与临床分期呈正相关。功能实验证明，敲低 ISG20 表达可明显抑制 ccRCC 细胞的生长、迁移和侵袭。为了寻找 ISG20 的潜在机制，进行了基因集富集分析（GSEA），结果表明，ISG20 高表达显著参与转移和细胞周期途径。此外，我们发现 ISG20 可以调节 MMP9 和 CCND1 的表达。总之，这些发现表明，ISG20 通过调节 MMP9/CCND1 表达促进细胞增殖和转移，可能成为 ccRCC 潜在的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/6e62e8b8b31d/aging-12-102714-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/d21a74f656ea/aging-12-102714-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/92d965dd4070/aging-12-102714-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/7c06f2a680b2/aging-12-102714-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/78cb51c3abdd/aging-12-102714-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/00981b85b0c3/aging-12-102714-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/526f43b46620/aging-12-102714-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/c94d5c8d415a/aging-12-102714-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/f184e5ea7aec/aging-12-102714-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/6e62e8b8b31d/aging-12-102714-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/d21a74f656ea/aging-12-102714-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/92d965dd4070/aging-12-102714-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/7c06f2a680b2/aging-12-102714-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/78cb51c3abdd/aging-12-102714-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/00981b85b0c3/aging-12-102714-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/526f43b46620/aging-12-102714-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/c94d5c8d415a/aging-12-102714-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/f184e5ea7aec/aging-12-102714-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d4/7053611/6e62e8b8b31d/aging-12-102714-g009.jpg

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