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通过多组学和基于网络的方法研究预后性线粒体自噬相关基因在非小细胞癌发病机制中的作用。

Investigating the role of prognostic mitophagy-related genes in non-small cell cancer pathogenesis via multiomics and network-based approach.

作者信息

Singh Prithvi, Tabassum Gulnaz, Masood Mohammad, Anwar Saleha, Syed Mansoor Ali, Dev Kapil, Hassan Md Imtaiyaz, Haque Mohammad Mahfuzul, Dohare Ravins, Singh Indrakant Kumar

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025 India.

Department of Biotechnology, Faculty of Life Sciences, Jamia Millia Islamia, New Delhi, 110025 India.

出版信息

3 Biotech. 2024 Nov;14(11):273. doi: 10.1007/s13205-024-04127-y. Epub 2024 Oct 21.

DOI:10.1007/s13205-024-04127-y
PMID:39444988
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11493942/
Abstract

UNLABELLED

As one of the most prevalent malignancies, lung cancer displays considerable biological variability in both molecular and clinical characteristics. Lung cancer is broadly categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) with the latter being most prevalent. The primary histological subtypes of NSCLC are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present work, we primarily extracted mRNA count data from a publicly accessible database followed by differentially expressed genes (DEGs) and differentially expressed mitophagy-related genes (DEMRGs) identification in case of both LUAD and LUSC cohorts. Next, we identified important DEMRGs via clustering approach followed by enrichment, survival, and mutational analyses. Lastly, the finalized prognostic biomarker was validated using wet-lab experimentations. Primarily, we obtained 986 and 1714 DEGs across LUAD and LUSC cohorts. Only 7 DEMRGs from both cohorts had significant membership values as indicated by the clustering analysis. Most significant pathway, Gene Ontology (GO)-biological process (BP), GO-molecular function (MF), GO-cellular compartment (CC) terms were macroautophagy, GTP metabolic process, magnesium ion binding, mitochondrial outer membrane. Among all, only reported significant overall survival (OS) and 14% amplification across LUAD patients. Lastly, we validated via immunohistochemistry (IHC) and semi-quantitative polymerase chain reaction (PCR). In conclusion, our findings advocate for the exploration of and their genetic alterations in precision oncology therapeutic approaches for LUAD, emphasizing the potential for target-driven therapy and early diagnostics

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s13205-024-04127-y.

摘要

未标注

作为最常见的恶性肿瘤之一,肺癌在分子和临床特征方面表现出相当大的生物学变异性。肺癌大致分为小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC),后者最为常见。NSCLC的主要组织学亚型是肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)。在本研究中,我们首先从一个可公开访问的数据库中提取mRNA计数数据,然后在LUAD和LUSC队列中进行差异表达基因(DEG)和差异表达的线粒体自噬相关基因(DEMRG)鉴定。接下来,我们通过聚类方法鉴定重要的DEMRG,随后进行富集、生存和突变分析。最后,使用湿实验室实验验证最终确定的预后生物标志物。首先,我们在LUAD和LUSC队列中分别获得了986个和1714个DEG。聚类分析表明,两个队列中只有7个DEMRG具有显著的成员值。最显著的通路、基因本体(GO)-生物学过程(BP)、GO-分子功能(MF)、GO-细胞区室(CC)术语是巨自噬、GTP代谢过程、镁离子结合、线粒体外膜。其中,只有 报告了LUAD患者的显著总生存期(OS)和14%的扩增率。最后,我们通过免疫组织化学(IHC)和半定量聚合酶链反应(PCR)对 进行了验证。总之,我们的研究结果主张在LUAD的精准肿瘤治疗方法中探索 及其基因改变,强调了靶向驱动治疗和早期诊断的潜力

补充信息

在线版本包含可在10.1007/s13205-024-04127-y获取的补充材料。

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