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采用整合式多平台分析方法研究实体瘤中的 基因突变。

Genetic Alterations of in Solid Tumors Using Integrative Multi-Platform Analysis.

机构信息

Laboratory of Molecular Pathology of Cancer, Faculty of Healthy Sciences, University of Brasília, Federal District, Brasília 70910-900, Brazil.

出版信息

Int J Mol Sci. 2024 May 31;25(11):6097. doi: 10.3390/ijms25116097.

DOI:10.3390/ijms25116097
PMID:38892284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11172816/
Abstract

SMYD4 is a member of the SMYD family that has lysine methyltransferase function. Little is known about the roles of in cancer. The aim of this study is to investigate genetic alterations in the gene across the most prevalent solid tumors and determine its potential as a biomarker. We performed an integrative multi-platform analysis of the most common mutations, copy number alterations (CNAs), and mRNA expression levels of the family genes using cohorts available at the Cancer Genome Atlas (TCGA), cBioPortal, and the Catalogue of Somatic Mutations in Cancer (COSMIC). genes displayed a lower frequency of mutations across the studied tumors, with none of the mutations detected demonstrating sufficient discriminatory power to serve as a biomarker. In terms of CNAs, consistently exhibited heterozygous loss and downregulation across all tumors evaluated. Moreover, showed low expression in tumor samples compared to normal samples, except for stomach adenocarcinoma. demonstrated a frequent negative correlation with other members of the family and a positive correlation between CNAs and mRNA expression. Additionally, patients with low expression in STAD and LUAD tumors exhibited significantly poorer overall survival. demonstrated its role as a tumor suppressor in the majority of tumors evaluated. The consistent downregulation of , coupled with its association with cancer progression, underscores its potential usefulness as a biomarker.

摘要

SMYD4 是具有赖氨酸甲基转移酶功能的 SMYD 家族的成员。目前对于在癌症中的作用知之甚少。本研究旨在研究在最常见的实体瘤中基因的遗传改变,并确定其作为生物标志物的潜力。我们使用癌症基因组图谱 (TCGA)、cBioPortal 和癌症体细胞突变目录 (COSMIC) 中可用的队列,对家族基因的最常见突变、拷贝数改变 (CNAs) 和 mRNA 表达水平进行了综合多平台分析。基因在研究的肿瘤中显示出较低的突变频率,没有检测到的任何突变显示出足够的区分能力作为生物标志物。就 CNAs 而言,在所有评估的肿瘤中均一致表现出杂合性丢失和下调。此外,与正常样本相比,肿瘤样本中的表达水平较低,除了胃腺癌。与家族的其他成员表现出频繁的负相关,与 mRNA 表达呈正相关。此外,在 STAD 和 LUAD 肿瘤中低表达的患者的总生存期明显较差。在大多数评估的肿瘤中表现出其作为肿瘤抑制因子的作用。的持续下调,加上其与癌症进展的关联,强调了其作为生物标志物的潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/65096743e3c2/ijms-25-06097-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/7f286e9fb5f5/ijms-25-06097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/4e5fc6725deb/ijms-25-06097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/f98f72b9b821/ijms-25-06097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/dabc7d98a775/ijms-25-06097-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/1c2eebaf0c75/ijms-25-06097-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/65096743e3c2/ijms-25-06097-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/7f286e9fb5f5/ijms-25-06097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/4e5fc6725deb/ijms-25-06097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/f98f72b9b821/ijms-25-06097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/dabc7d98a775/ijms-25-06097-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/1c2eebaf0c75/ijms-25-06097-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3b/11172816/65096743e3c2/ijms-25-06097-g006.jpg

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Exp Mol Med. 2023 Dec;55(12):2475-2497. doi: 10.1038/s12276-023-01117-7. Epub 2023 Dec 1.
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The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer.
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