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一项系统分析揭示,血清剥夺反应(SDPR)基因的表达改变与癌症患者的生存显著相关。

A systematic analysis reveals gene expression alteration of serum deprivation response (SDPR) gene is significantly associated with the survival of patients with cancer.

机构信息

College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.

Peking University Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, P.R. China.

出版信息

Oncol Rep. 2019 Sep;42(3):1161-1172. doi: 10.3892/or.2019.7212. Epub 2019 Jun 26.

Abstract

Serum deprivation response (SDPR) gene has been recently characterized as a gene signature marker or serving a tumor suppressor role in specific types of cancer. However, gene expression alterations of SDPR in various types of cancer and their relevance to clinical outcomes remain unclear. In the present study, SDPR expression was profiled using the Oncomine database, and SDPR downregulation was indicated in most types of cancer. In agreement with previously reported breast cancer cases, downregulation of SDPR was indicated to be significantly associated with poor survival in patients with lung cancer, glioma and sarcoma. To clarify why SDPR expression was altered in these types of cancer, both DNA methylation patterns and potential transcriptional factors of SDPR were analyzed. Altered DNA methylation levels of SDPR were found in 17/18 cancer types using MethHC. To the best of our knowledge, the present study for the first time, identified the CpG site (cg10082589) as one of the best survival methylation markers for lung adenocarcinoma, and the CpG site (cg07488576) for sarcoma using Methsurv. In addition, GATA binding protein 2 was identified as a potential transcription factor for SDPR, by integrating and analyzing both the co‑expressed genes and the potential transcription factor binding sites of SDPR. In the present study, the systematic analysis of SDPR provided insight for the underlying molecular mechanisms in cancer progression, revealing novel perspectives for the clinical prognostic evaluation of lung adenocarcinoma and sarcoma.

摘要

血清剥夺反应 (SDPR) 基因最近被描述为特定类型癌症中的基因特征标志物或肿瘤抑制因子。然而,SDPR 在各种类型癌症中的基因表达改变及其与临床结果的相关性尚不清楚。在本研究中,使用 Oncomine 数据库对 SDPR 表达进行了分析,结果表明大多数类型的癌症中 SDPR 下调。与先前报道的乳腺癌病例一致,SDPR 的下调与肺癌、神经胶质瘤和肉瘤患者的不良生存显著相关。为了阐明为什么这些类型的癌症中 SDPR 的表达发生改变,分析了 SDPR 的 DNA 甲基化模式和潜在转录因子。使用 MethHC 发现 17/18 种癌症类型中的 SDPR 存在改变的 DNA 甲基化水平。据我们所知,本研究首次确定了 cg10082589 作为肺腺癌最佳生存甲基化标志物之一,以及 cg07488576 作为肉瘤的最佳生存甲基化标志物之一。此外,通过整合和分析 SDPR 的共表达基因和潜在转录因子结合位点,确定 GATA 结合蛋白 2 是 SDPR 的潜在转录因子。在本研究中,对 SDPR 的系统分析为癌症进展的潜在分子机制提供了深入了解,为肺腺癌和肉瘤的临床预后评估提供了新的视角。

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