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鉴定和验证与糖酵解相关的六个基因标志物,以预测宫颈癌患者的预后。

Identification and validation of a six-gene signature associated with glycolysis to predict the prognosis of patients with cervical cancer.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang, 325000, P.R. China.

Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266071, China.

出版信息

BMC Cancer. 2020 Nov 23;20(1):1133. doi: 10.1186/s12885-020-07598-3.

Abstract

BACKGROUND

Cervical cancer (CC) is one of the most common gynaecological cancers. The gene signature is believed to be reliable for predicting cancer patient survival. However, there is no relevant study on the relationship between the glycolysis-related gene (GRG) signature and overall survival (OS) of patients with CC.

METHODS

We extracted the mRNA expression profiles of 306 tumour and 13 normal tissues from the University of California Santa Cruz (UCSC) Database. Then, we screened out differentially expressed glycolysis-related genes (DEGRGs) among these mRNAs. All patients were randomly divided into training cohort and validation cohort according to the ratio of 7: 3. Next, univariate and multivariate Cox regression analyses were carried out to select the GRG with predictive ability for the prognosis of the training cohort. Additionally, risk score model was constructed and validated it in the validation cohort.

RESULTS

Six mRNAs were obtained that were associated with patient survival. The filtered mRNAs were classified into the protective type (GOT1) and the risk type (HSPA5, ANGPTL4, PFKM, IER3 and PFKFB4). Additionally, by constructing the prognostic risk score model, we found that the OS of the high-risk group was notably poorer, which showed good predictive ability both in training cohort and validation cohort. And the six-gene signature is a prognostic indicator independent of clinicopathological features. Through the verification of PCR, the results showed that compared with the normal cervial tissuses, the expression level of six mRNAs were significantly higher in the CC tissue, which was consistent with our findings.

CONCLUSIONS

We constructed a glycolysis-related six-gene signature to predict the prognosis of patients with CC using bioinformatics methods. We provide a thorough comprehension of the effect of glycolysis in patients with CC and provide new targets and ideas for individualized treatment.

摘要

背景

宫颈癌(CC)是最常见的妇科癌症之一。基因特征被认为是预测癌症患者生存的可靠指标。然而,目前尚无关于糖酵解相关基因(GRG)特征与 CC 患者总生存期(OS)之间关系的相关研究。

方法

我们从加利福尼亚大学圣克鲁兹分校(UCSC)数据库中提取了 306 个肿瘤和 13 个正常组织的 mRNA 表达谱。然后,我们筛选出这些 mRNA 中差异表达的糖酵解相关基因(DEGRGs)。所有患者根据 7:3 的比例随机分为训练队列和验证队列。接下来,对训练队列进行单因素和多因素 Cox 回归分析,以选择对预后有预测能力的 GRG。此外,在验证队列中构建并验证风险评分模型。

结果

获得了 6 个与患者生存相关的 mRNA。筛选出的 mRNA 分为保护型(GOT1)和风险型(HSPA5、ANGPTL4、PFKM、IER3 和 PFKFB4)。此外,通过构建预后风险评分模型,我们发现高危组的 OS 明显较差,在训练队列和验证队列中均具有良好的预测能力。并且该 6 基因特征是独立于临床病理特征的预后指标。通过 PCR 验证,结果表明与正常宫颈组织相比,CC 组织中 6 个 mRNA 的表达水平显著升高,与我们的研究结果一致。

结论

我们使用生物信息学方法构建了一个糖酵解相关的 6 基因特征,用于预测 CC 患者的预后。我们深入了解了糖酵解在 CC 患者中的作用,并为个体化治疗提供了新的靶点和思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a338/7686733/4ec95191dabf/12885_2020_7598_Fig1_HTML.jpg

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