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用于肺鳞状细胞癌预后的DNA损伤修复基因相关特征的鉴定。

Identification of a DNA damage repair gene-related signature for lung squamous cell carcinoma prognosis.

作者信息

Jia Bin, Gong Ting, Sun Bingsheng, Zhang Zhenfa, Zhong Diansheng, Wang Changli

机构信息

Department of Lung Cancer, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Thorac Cancer. 2022 Apr;13(8):1143-1152. doi: 10.1111/1759-7714.14370. Epub 2022 Mar 15.

Abstract

BACKGROUND

DNA damage repair (DDR) plays a role in the tumorigenesis and progression of lung squamous cell carcinoma (LUSC), but the predictive value of DDR in LUSC has not been fully elucidated.

METHODS

The LUSC datasets were retrieved from the Cancer Genome Atlas databases. Univariate Cox regression and least absolute shrinkage and selection operator regression were integrated to identify critical genes and construct a DDR gene signature. We performed Kaplan-Meier (KM) curve to compare the overall survival (OS) between the two groups based on DDR signature and used the CIBERSORT tool to compare the immune cell composition. Further gene set enrichment analysis (GSEA) was performed on the differential expressed genes.

RESULT

We established the DDR-related gene signature on LUSC. KM curve showed the low-risk group had a better prognosis than the high-risk group in the training set (p = 0.022673) and the complete set (p = 0.003201). The area under receiver operating characteristic curve for OS was 0.98, 0.96, and 0.97 in the training dataset, testing dataset, and the complete dataset, respectively. The composition of immune cells was different between the high- and low-risk group. The GSEA result suggests that genes of the patients in low-risk group were mainly enriched in the DNA adducts; drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450.

CONCLUSION

This study identified DDR-associated potential biomarkers related to overall survival of LUSC and establishes the DDR-associated gene signature.

摘要

背景

DNA损伤修复(DDR)在肺鳞状细胞癌(LUSC)的肿瘤发生和进展中起作用,但DDR在LUSC中的预测价值尚未完全阐明。

方法

从癌症基因组图谱数据库中检索LUSC数据集。整合单变量Cox回归和最小绝对收缩和选择算子回归以鉴定关键基因并构建DDR基因特征。我们进行了Kaplan-Meier(KM)曲线以比较基于DDR特征的两组之间的总生存期(OS),并使用CIBERSORT工具比较免疫细胞组成。对差异表达基因进行进一步的基因集富集分析(GSEA)。

结果

我们在LUSC上建立了DDR相关基因特征。KM曲线显示,在训练集(p = 0.022673)和完整集中,低风险组的预后优于高风险组(p = 0.003201)。训练数据集、测试数据集和完整数据集中OS的受试者工作特征曲线下面积分别为0.98、0.96和0.97。高风险组和低风险组之间的免疫细胞组成不同。GSEA结果表明,低风险组患者的基因主要富集于DNA加合物;药物代谢 - 细胞色素P450,细胞色素P450对外源生物的代谢。

结论

本研究鉴定了与LUSC总生存期相关的DDR相关潜在生物标志物,并建立了DDR相关基因特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f49/9013644/03cab72c677f/TCA-13-1143-g005.jpg

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