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.
Authors
- Jian‐Ying Chuang (ORCID: https://orcid.org/0000-0001-5124-0643)
- Do Thi Minh Xuan
- Ching‐Chung Ko (ORCID: https://orcid.org/0000-0002-8950-7128)
- Chih‐Yang Wang (ORCID: https://orcid.org/0000-0002-4137-5074)
- Lidya Kristiani (ORCID: https://orcid.org/0000-0001-6611-1297)
- Chung-Chieh Chiao
- Damtew Solomon (ORCID: https://orcid.org/0000-0003-4831-4992)
- Hung‐Yun Lin (ORCID: https://orcid.org/0000-0003-2824-6419)
- Chung-Che Wu
- Michael Michael (ORCID: https://orcid.org/0000-0001-5954-7105)
- Sachin Kumar
- Carter Rebecca
- Fitria Sari Wulandari
- Ming-Cheng Tsai
- Juan Lorell Ngadio
Institutions
- Fu Jen Catholic University (TW)
- National Sun Yat-sen University (TW)
- Kaohsiung Medical University (TW)
- Atma Jaya Catholic University of Indonesia (ID)
- Taipei Medical University Hospital (TW)
- Albany College of Pharmacy and Health Sciences (US)
- Van Lang University (VN)
- Shoolini University (IN)
- Chi Mei Medical Center (TW)
- Indonesia International Institute for Life Sciences (ID)
- Wan Fang Hospital (TW)
- Taipei Medical University-Shuang Ho Hospital (TW)
- Memorial Hospital (US)
- Taipei Medical University (TW)
- Chia Nan University of Pharmacy and Science (TW)
Publication Details
- Journal
- Journal of Cancer
- Published
- 2025-04-13
- DOI
- https://doi.org/10.7150/jca.106902
- Citations
- 5
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- Academia Sinica
- Ministry of Education, India
- Taipei Medical University
- National Science and Technology Council
- Taipei Medical University Hospital