多组学和单细胞转录组的整合揭示了线粒体外膜蛋白-2 (MTX-2)作为肺腺癌预后的生物标志物和泛素代谢的特征。

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-04-13 eCollection Date: 2025-01-01 DOI:10.7150/jca.106902
Sachin Kumar, Chung-Che Wu, Fitria Sari Wulandari, Chung-Chieh Chiao, Ching-Chung Ko, Hung-Yun Lin, Juan Lorell Ngadio, Cathleen Rebecca, Do Thi Minh Xuan, Dahlak Daniel Solomon, Michael Michael, Lidya Kristiani, Jian-Ying Chuang, Ming-Cheng Tsai, Chih-Yang Wang
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引用次数: 0

摘要

肺腺癌(LUAD)仍然是最普遍和高度侵袭性的癌症之一。线粒体外膜蛋白-2或Metaxin-2 (MTX2)是线粒体功能的关键调节因子,与细胞生物能量学和应激反应机制有关。然而,其在LUAD的进展和预后中的作用仍未被广泛探索。本研究采用多组学方法,整合公共数据库的转录组学和临床患者数据,评估MTX2在LUAD中的表达和预后相关性。利用单细胞RNA测序进一步探索MTX2在肿瘤微环境免疫浸润和相互作用中的作用。此外,我们通过一系列分子生物学和功能分析验证了这些发现。我们的研究结果表明,MTX2在LUAD组织中的表达高于正常肺组织。MTX2水平升高与LUAD患者较差的总生存期显著相关。功能分析显示MTX2调节线粒体生物能量,促进肿瘤细胞增殖。此外,MTX2的表达与免疫细胞浸润增加有关。通路分析发现MTX2调节细胞代谢和肿瘤生长通路,支持其在肿瘤进展中的作用。我们的研究确定MTX2是一种有希望的LUAD预后生物标志物和治疗靶点。MTX2的表达增加通过改变代谢途径和调节免疫反应来促进肿瘤生长,强调其作为LUAD治疗的新靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integration of multi-omics and single-cell transcriptome reveals mitochondrial outer membrane protein-2 (MTX-2) as a prognostic biomarker and characterizes ubiquinone metabolism in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains to be one of the most prevalent and highly invasive forms of cancer. Mitochondrial outer membrane protein-2 or Metaxin-2 (MTX2), a key regulator of mitochondrial function, has been linked to cellular bioenergetics and stress response mechanisms. However, its roles in the progression and prognosis of LUAD remain largely unexplored. This study, employed a multi-omics approach, integrating transcriptomic and clinical patient data from public databases, to evaluate the expression and prognostic relevance of MTX2 in LUAD. Single-cell RNA sequencing was utilized to further explore MTX2's role in immune infiltration and interactions within the tumor microenvironment. Additionally, we validated these findings through a series of molecular biology and functional assays. Our results demonstrated that MTX2 expression was higher in LUAD tissues compared to normal lung tissues. Elevated MTX2 levels were significantly associated with poorer overall survival in LUAD patients. Functional analyses revealed that MTX2 regulates mitochondrial bioenergetics and facilitates tumor cell proliferation. Additionally, MTX2 expression was associated with increased immune cell infiltration. A pathway analysis identified cell metabolic and tumor growth pathways regulated by MTX2, supporting its role in tumor progression. Our research identifies MTX2 as a promising prognostic biomarker and therapeutic target for LUAD. Increased expression of MTX2 promotes tumor growth by altering metabolic pathways and modulating the immune response, underscoring its potential as a new target for LUAD treatment.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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