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
{"title":"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。","authors":"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","doi":"10.7150/jca.106902","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2401-2420"},"PeriodicalIF":3.3000,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036103/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.7150/jca.106902\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":15183,\"journal\":{\"name\":\"Journal of Cancer\",\"volume\":\"16 7\",\"pages\":\"2401-2420\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036103/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/jca.106902\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/jca.106902","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.