Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer.

IF 3.5 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Cong Fu, Lin Sun, Xiaoyue Zhou, Tong Zhou, Yanzhi Bi
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Abstract

Mitochondrial-related nuclear genes (MNGs) have shown great importance in cancer diagnosis and prognosis, but their role in gastric cancer (GC) remains unclear. GC-related transcriptome data from the gene expression omnibus and cancer genome atlas databases were analyzed to identify differentially expressed MNGs. A prognostic risk model was constructed through univariate Cox and least absolute shrinkage and selection operator regression, validated by Kaplan-Meier (K-M) survival curve and receiver operating characteristic curve. This was followed by immune infiltration analysis, independent prognostic analysis, functional enrichment analysis, drug sensitivity analysis, drug prediction, molecular docking and construction of regulatory networks. Three prognostic genes (ATP8A2, COX15 and TARS2) were identified. The expression of TARS2 and COX15 was positively correlated with CNV, while ATP8A2 was unaffected. The risk model and nomogram, integrating risk score and clinicopathological factors, exhibited excellent predictive performance. A significant correlation was observed between prognostic genes and differential immune cells, such as T cells, B cells, and NK cells. BMS-754807, Gefitinib, JQ1, Lapatinib, and Sapitinib exhibited significant differences in sensitivity between the high-risk group and the low-risk group. The results of molecular docking showed TP8A2 has stable binding ability with cytosine, COX15 with indomethacin, and TARS2 with bisacodyl. RT-qPCR revealed downregulation of ATP8A2 and upregulation of COX15 and TARS2 in GC samples. MNGs, including ATP8A2, COX15, and TARS2, demonstrated significant associations with immune infiltration, CNV, and prognostic outcomes of GC.

胃癌线粒体核基因相关预后基因的鉴定与验证。
线粒体相关核基因(MNGs)在癌症诊断和预后中具有重要意义,但其在胃癌(GC)中的作用尚不清楚。分析来自基因表达综合数据库和癌症基因组图谱数据库的gc相关转录组数据,以鉴定差异表达的MNGs。通过单变量Cox、最小绝对收缩和选择算子回归构建预后风险模型,并通过Kaplan-Meier (K-M)生存曲线和受试者工作特征曲线进行验证。随后进行免疫浸润分析、独立预后分析、功能富集分析、药物敏感性分析、药物预测、分子对接和调控网络构建。鉴定出3个预后基因(ATP8A2、COX15和TARS2)。TARS2和COX15的表达与CNV呈正相关,而ATP8A2不受影响。综合风险评分和临床病理因素的风险模型和nomogram具有较好的预测效果。预后基因与差异免疫细胞(如T细胞、B细胞和NK细胞)之间存在显著相关性。BMS-754807、吉非替尼、JQ1、拉帕替尼、沙匹替尼在高危组和低危组之间的敏感性有显著差异。分子对接结果显示,TP8A2与胞嘧啶、COX15与吲哚美辛、TARS2与比沙代碱具有稳定的结合能力。RT-qPCR结果显示GC样品中ATP8A2下调,COX15和TARS2上调。包括ATP8A2、COX15和TARS2在内的mgs与免疫浸润、CNV和胃癌预后有显著相关性。
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
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