Constructe a novel 5 hypoxia genes signature for cervical cancer.
Constructe a novel 5 hypoxia genes signature for cervical cancer.
复制标题
构建宫颈癌的 5 个新缺氧基因特征
DOI：
10.1186/s12935-021-02050-3
复制
发表时间：
2021-07-03
影响因子：
5.8
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Yang Y;Li Y;Qi R;Zhang L
缺氧是癌症的一个重要特征，它影响癌症的发展、转移和预后。本研究建立了一个缺氧危险因素模型，用于预测宫颈癌的预后。根据缺氧通路相关基因，我们将宫颈癌样本分为高表达组和低表达组。然后进行考克斯分析。从这些宫颈癌样品中选择对OS显示显著影响的基因进行聚类分析，以获得两种亚型。TCGA的TPM数据集分为训练集和验证集。对于训练集，基于有意义基因的考克斯分析进行lasso分析，并构建风险因素模型。所构建的模型在内部和外部数据集进行了验证。最后，采用RT-PCR、免疫组化等方法检测相关基因或蛋白的表达，并通过功能分析对标签基因的生物学功能进行评价。共获得149个符合该标准的DEG（Differential expressed genes），其中27个表达上调，122个表达下调。选择λ = 0.0571的五个基因构建模型，RiskScore = AK 4 *0.042 + HK 2 *0.021 + P4 HA 1 *0.22 + TGFBI*0.1 + VEGFA*0.077。进一步，为了验证签名的有效性，我们使用TCGA-test和GSE 44001芯片数据集进行测试，最终在这些数据集上得到了良好的风险预测效果。RT-PCR和免疫组化结果显示AK 4、HK 2、P4 HA 1、TGFBI和VEGFA在宫颈癌组织中均呈高表达。功能研究表明，AK 4、HK 2、P4 HA 1、TGFBI和VEGFA的表达可调节宫颈癌细胞的体外增殖、迁移和侵袭能力。综上所述，我们开发了一个基于宫颈癌缺氧通路的5基因标记预后分级系统，该系统独立于临床特征。并对这些特征基因进行了实验验证。因此，我们建议使用这种分类器作为一种分子诊断测试可以提供一种有效的手段来评估宫颈癌患者的预后风险，并为宫颈癌患者的治疗提供潜在的目标。在线版本包含补充材料，可通过10.1186/s12935-021-02050-3获得。
Hypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer. Based on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes. Two molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro. In summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients. The online version contains supplementary material available at 10.1186/s12935-021-02050-3.
登录
查看更多内容
影响因子：
4
作者：
Pourhanifeh MH;Darvish M;Tabatabaeian J;Fard MR;Mottaghi R;Azadchehr MJ;Jahanshahi M;Sahebkar A;Mirzaei H
通讯作者：
Mirzaei H
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
影响因子：
11.5
作者：
Brooks, Jill M.;Menezes, Albert N.;Mehanna, Hisham
通讯作者：
Mehanna, Hisham
DOI：
10.1186/s13046-019-1418-2
发表时间：
2019-10-26
影响因子：
11.3
作者：
Ou, Baochi;Sun, Hongze;Peng, Zhihai
通讯作者：
Peng, Zhihai
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--