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用于预测卵巢癌总生存期的铁死亡相关基因模型

Ferroptosis-Related Gene Model to Predict Overall Survival of Ovarian Carcinoma.

作者信息

Yang Liuqing, Tian Saisai, Chen Yun, Miao Chenyun, Zhao Ying, Wang Ruye, Zhang Qin

机构信息

Guangxing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310007, China.

Department of Phytochemistry, School of Pharmacy, The Second Military Medical University, Shanghai 200433, China.

出版信息

J Oncol. 2021 Jan 13;2021:6687391. doi: 10.1155/2021/6687391. eCollection 2021.

Abstract

BACKGROUND

Ovarian cancer (OC) is the eighth most common cause of cancer death and the second cause of gynecologic cancer death in women around the world. Ferroptosis, an iron-dependent regulated cell death, plays a vital role in the development of many cancers. Applying expression of ferroptosis-related gene to forecast the cancer progression is helpful for cancer treatment. However, the relationship between ferroptosis-related genes and OC patient prognosis is still vastly unknown, making it still a challenge for developing ferroptosis therapy for OC.

METHODS

The Cancer Genome Atlas (TCGA) data of OC were obtained and the datasets were randomly divided into training and test datasets. A novel ferroptosis-related gene signature associated with overall survival (OS) was constructed according to the training cohort. The test dataset and ICGC dataset were used to validate this signature.

RESULTS

We constructed a model containing nine ferroptosis-related genes, namely, , , , , , , , , and , and predicted the OS of OC in TCGA. At a suitable cutoff, patients were divided into low risk and high risk groups. The OS curves of the two groups of patients had significant differences, and the time-dependent receiver operating characteristics (ROCs) were as high as 0.664, respectively. Then, the test dataset and the ICGC dataset were used to evaluate our model, and the ROCs of test dataset were 0.667 and 0.777, respectively. In addition, functional analysis and correlation analysis showed that immune-related pathways were significantly enriched. Meanwhile, we also integrated with other clinical factors and we found the synthesized clinical factors and ferroptosis-related gene signature improved prognostic accuracy relative to the ferroptosis-related gene signature alone.

CONCLUSION

The ferroptosis-related gene signature could predict the OS of OC patients and improve therapeutic decision-making.

摘要

背景

卵巢癌(OC)是全球女性癌症死亡的第八大常见原因,也是妇科癌症死亡的第二大原因。铁死亡是一种铁依赖性调节性细胞死亡,在许多癌症的发展中起着至关重要的作用。应用铁死亡相关基因的表达来预测癌症进展有助于癌症治疗。然而,铁死亡相关基因与OC患者预后之间的关系仍然知之甚少,这使得开发针对OC的铁死亡疗法仍然是一个挑战。

方法

获取OC的癌症基因组图谱(TCGA)数据,并将数据集随机分为训练集和测试集。根据训练队列构建了一个与总生存期(OS)相关的新型铁死亡相关基因特征。使用测试数据集和ICGC数据集来验证该特征。

结果

我们构建了一个包含九个铁死亡相关基因的模型,即 、 、 、 、 、 、 、 、 ,并预测了TCGA中OC的OS。在合适的临界值下,将患者分为低风险和高风险组。两组患者的OS曲线有显著差异,时间依赖性受试者工作特征(ROC)分别高达0.664。然后,使用测试数据集和ICGC数据集评估我们的模型,测试数据集的ROC分别为0.667和0.777。此外,功能分析和相关性分析表明免疫相关途径显著富集。同时,我们还将其与其他临床因素相结合,发现合成的临床因素和铁死亡相关基因特征相对于单独的铁死亡相关基因特征提高了预后准确性。

结论

铁死亡相关基因特征可以预测OC患者的OS并改善治疗决策。

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