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基于铜死亡相关基因构建预后模型并探讨DLAT和DLST在非小细胞肺癌转移中的价值

Construction of a prognostic model based on cuproptosis-related genes and exploration of the value of DLAT and DLST in the metastasis for non-small cell lung cancer.

作者信息

Ma Huiying, Ge Yizhi, Li Yuhong, Wang Tingting, Chen Wei

机构信息

Department of Radiation Oncology, The First People's Hospital of Jiande, Hangzhou, China.

Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China.

出版信息

Medicine (Baltimore). 2024 Dec 6;103(49):e40727. doi: 10.1097/MD.0000000000040727.

Abstract

BACKGROUND

To reveal the clinical value of cuproptosis-related genes on prognosis and metastasis in non-small cell lung cancer.

METHODS

Gene expression profiles and clinical information of non-small cell lung cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The data were grouped into training set, internal testing set, and external testing set. A risk prognostic model was constructed by Lasso-Cox regression analysis. Hub genes were identified and evaluated using immunohistochemistry and the transwell migration assay in 50 clinical patients.

RESULTS

A total of 17/19 cuproptosis-related genes were differentially expressed in tumors, 8 were significantly associated with prognosis, and 4 were markedly associated with metastasis. A risk model based on 2 cuproptosis-related genes was constructed and validated for predicting overall survival. The risk score was proven to be an independent risk factor for the prognosis of non-small cell lung cancer. Dihydrolipoamide S-acetyltransferase and dihydrolipoamide S-succinyltransferase, key genes in cuproptosis, were proven to be associated with non-small cell lung cancer prognosis and metastasis. Immunohistochemistry showed that their expression significantly predicted metastasis but failed to predict prognosis in non-small cell lung cancer patients. The transwell migration assay further increased the cellular reliability of our findings.

CONCLUSION

The cuproptosis-related genes prognostic model effectively predicted the prognosis of non-small cell lung cancer. Dihydrolipoamide S-acetyltransferase and dihydrolipoamide S-succinyltransferase may serve as predictive markers for metastasis in non-small cell lung cancer.

摘要

背景

揭示铜死亡相关基因在非小细胞肺癌预后和转移中的临床价值。

方法

从癌症基因组图谱(The Cancer Genome Atlas)和基因表达综合数据库(Gene Expression Omnibus)下载非小细胞肺癌的基因表达谱和临床信息。将数据分为训练集、内部测试集和外部测试集。通过套索-考克斯回归分析构建风险预后模型。使用免疫组织化学和transwell迁移试验对50例临床患者的枢纽基因进行鉴定和评估。

结果

19个铜死亡相关基因中有17个在肿瘤中差异表达,8个与预后显著相关,4个与转移显著相关。构建并验证了基于2个铜死亡相关基因的风险模型以预测总生存期。风险评分被证明是非小细胞肺癌预后的独立危险因素。铜死亡中的关键基因二氢硫辛酰胺S-乙酰转移酶和二氢硫辛酰胺S-琥珀酰转移酶被证明与非小细胞肺癌的预后和转移相关。免疫组织化学显示它们的表达可显著预测非小细胞肺癌患者的转移,但不能预测预后。transwell迁移试验进一步提高了我们研究结果的细胞可靠性。

结论

铜死亡相关基因预后模型有效预测了非小细胞肺癌的预后。二氢硫辛酰胺S-乙酰转移酶和二氢硫辛酰胺S-琥珀酰转移酶可能作为非小细胞肺癌转移的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b0e/11631004/3a588dba8b6f/medi-103-e40727-g001.jpg

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