A novel mitochondria-related algorithm for predicting the survival outcomes and drug sensitivity of patients with lung adenocarcinoma

IF 3.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Frontiers in Molecular Biosciences Pub Date : 2024-08-08 DOI:10.3389/fmolb.2024.1397281
Xianqiao Wu, Hang Chen, Zhen Ge, Binyu Luo, Hanbo Pan, Yiming Shen, Zuorun Xie, Chengwei Zhou
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Abstract

Mitochondria have always been considered too be closely related to the occurrence and development of malignant tumors. However, the bioinformatic analysis of mitochondria in lung adenocarcinoma (LUAD) has not been reported yet.In the present study, we constructed a novel and reliable algorithm, comprising a consensus cluster analysis and risk assessment model, to predict the survival outcomes and tumor immunity for patients with terminal LUAD.Patients with LUAD were classified into three clusters, and patients in cluster 1 exhibited the best survival outcomes. The patients in cluster 3 had the highest expression of PDL1 (encoding programmed cell death 1 ligand 11) and HAVCR2 (encoding Hepatitis A virus cellular receptor 2), and the highest tumor mutation burden (TMB). In the risk assessment model, patients in the low-risk group tended to have a significantly better survival outcome. Furthermore, the risk score combined with stage could act as a reliable independent prognostic indicator for patients with LUAD. The prognostic signature is a novel and effective biomarker to select anti-tumor drugs. Low-risk patients tended to have a higher expression of CTLA4 (encoding cytotoxic T-lymphocyte associated protein 4) and HAVCR2. Moreover, patients in the high-risk group were more sensitive to Cisplatin, Docetaxel, Erlotinib, Gemcitabine, and Paclitaxel, while low-risk patients would probably benefit more from Gefitinib.We constructed a novel and reliable algorithm comprising a consensus cluster analysis and risk assessment model to predict survival outcomes, which functions as a reliable guideline for anti-tumor drug treatment for patients with terminal LUAD.
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预测肺腺癌患者生存结果和药物敏感性的线粒体相关新算法
线粒体一直被认为与恶性肿瘤的发生和发展密切相关。在本研究中,我们构建了一种新颖可靠的算法,包括共识聚类分析和风险评估模型,用于预测晚期肺腺癌患者的生存结果和肿瘤免疫力。第3组患者的PDL1(编码程序性细胞死亡1配体11)和HAVCR2(编码甲型肝炎病毒细胞受体2)表达量最高,肿瘤突变负荷(TMB)也最高。在风险评估模型中,低风险组患者的生存率明显更高。此外,风险评分与分期相结合可作为LUAD患者可靠的独立预后指标。预后特征是选择抗肿瘤药物的一种新颖而有效的生物标志物。低危患者的CTLA4(编码细胞毒性T淋巴细胞相关蛋白4)和HAVCR2表达量较高。此外,高风险组患者对顺铂、多西他赛、厄洛替尼、吉西他滨和紫杉醇更敏感,而低风险组患者可能从吉非替尼中获益更多。
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来源期刊
Frontiers in Molecular Biosciences
Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
7.20
自引率
4.00%
发文量
1361
审稿时长
14 weeks
期刊介绍: Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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