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鉴定一种与肿瘤微环境相关的基因特征以改善宫颈癌预后预测

Identification of a tumor microenvironment-related gene signature to improve the prediction of cervical cancer prognosis.

作者信息

Chen Qian, Qiu Bingqing, Zeng Xiaoyun, Hu Lang, Huang Dongping, Chen Kaihua, Qiu Xiaoqiang

机构信息

Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, China.

Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.

出版信息

Cancer Cell Int. 2021 Mar 25;21(1):182. doi: 10.1186/s12935-021-01867-2.

Abstract

BACKGROUND

Previous studies have found that the microenvironment of cervical cancer (CESC) affects the progression and treatment of this disease. Thus, we constructed a multigene model to assess the survival of patients with cervical cancer.

METHODS

We scored 307 CESC samples from The Cancer Genome Atlas (TCGA) and divided them into high and low matrix and immune scores using the ESTIMATE algorithm for differential gene analysis. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The multigene signature prognostic model was constructed by Cox analyses. Multivariate Cox analysis was applied to evaluate the significance of the multigene signature for cervical cancer prognosis. Prognosis was assessed by Kaplan-Meier curves comparing the different groups, and the accuracy of the prognostic model was analyzed by receiver operating characteristic-area under the curve (ROC-AUC) analysis and calibration curve. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between the multigene signature and immune cell infiltration.

RESULTS

We obtained 420 differentially expressed genes in the tumor microenvironment from 307 patients with cervical cancer. A three-gene signature (SLAMF1, CD27, SELL) model related to the tumor microenvironment was constructed to assess patient survival. Kaplan-Meier analysis showed that patients with high risk scores had a poor prognosis. The ROC-AUC value indicated that the model was an accurate predictor of cervical cancer prognosis. Multivariate cox analysis showed the three-gene signature to be an independent risk factor for the prognosis of cervical cancer. A nomogram combining the three-gene signature and clinical features was constructed, and calibration plots showed that the nomogram resulted in an accurate prognosis for patients. The three-gene signature was associated with T stage, M stage and degree of immune infiltration in patients with cervical cancer.

CONCLUSIONS

This research suggests that the developed three-gene signature may be applied as a biomarker to predict the prognosis of and personalized therapy for CESC.

摘要

背景

既往研究发现,宫颈癌(CESC)的微环境会影响该疾病的进展和治疗。因此,我们构建了一个多基因模型来评估宫颈癌患者的生存情况。

方法

我们对来自癌症基因组图谱(TCGA)的307份CESC样本进行评分,并使用ESTIMATE算法进行差异基因分析,将其分为高、低基质和免疫评分组。宫颈癌患者被随机分为训练组、测试组和联合组。通过Cox分析构建多基因特征预后模型。应用多变量Cox分析评估多基因特征对宫颈癌预后的意义。通过比较不同组的Kaplan-Meier曲线评估预后,并通过受试者工作特征曲线下面积(ROC-AUC)分析和校准曲线分析预后模型的准确性。使用肿瘤免疫估计资源(TIMER)数据库分析多基因特征与免疫细胞浸润之间的关系。

结果

我们从307例宫颈癌患者的肿瘤微环境中获得了420个差异表达基因。构建了一个与肿瘤微环境相关的三基因特征(SLAMF1、CD27、SELL)模型来评估患者生存情况。Kaplan-Meier分析表明,高风险评分的患者预后较差。ROC-AUC值表明该模型是宫颈癌预后的准确预测指标。多变量cox分析表明三基因特征是宫颈癌预后的独立危险因素。构建了一个结合三基因特征和临床特征的列线图,校准图显示该列线图能准确预测患者的预后。三基因特征与宫颈癌患者的T分期、M分期和免疫浸润程度相关。

结论

本研究表明,所开发的三基因特征可作为一种生物标志物,用于预测CESC的预后和个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75bb/7992856/59df34105af7/12935_2021_1867_Fig1_HTML.jpg

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