Huang Yi-Hui, Chang Wen-Hsin, Shen Chi-Ya, Su Kang-Yi, Chang Gee-Chen, Chen Jin-Shing, Lee Wen-Yao, Chen Yu-Ju, Yu Sung-Liang
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10048, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100233, Taiwan.
J Proteome Res. 2025 Aug 1;24(8):4139-4153. doi: 10.1021/acs.jproteome.5c00273. Epub 2025 Jul 21.
Given the limited proteomic insights and high incidence of lung adenocarcinoma, further investigation of uncharacterized proteins in cancer progression remains crucial. In this study, a poorly characterized protein, OCIA domain-containing 2 (OCIAD2), encoded by chromosome 4 was identified as being upregulated in lung adenocarcinoma from our previous proteogenomics data using the Taiwan Cancer Moonshot cohort. OCIAD2 was highly expressed in tumor tissues in 95.5% of lung adenocarcinoma patients in our cohort, with elevated expression correlating with worse survival. Functional studies revealed that the silencing of the OCIAD2 decreased cell migration, invasion, and colony-forming abilities. Gene Set Enrichment Analysis (GSEA) indicated the involvement of OCIAD2 in oxidative phosphorylation (OXPHOS). Subsequently, mitochondrial metabolic assay demonstrated that OCIAD2 impairs OXPHOS function, accompanied by a metabolic shift toward glycolysis. These findings suggest that OCIAD2 promotes cancer progression through metabolic reprogramming, highlighting the role of OCIAD2 as a potential biomarker and therapeutic target for lung adenocarcinoma.
鉴于蛋白质组学方面的见解有限以及肺腺癌的高发病率,进一步研究癌症进展中未被表征的蛋白质仍然至关重要。在本研究中,利用台湾癌症登月计划队列的先前蛋白质基因组学数据,我们从4号染色体编码的一种特征不明的蛋白质——含OCIAD结构域2(OCIAD2)中发现,它在肺腺癌中上调。在我们的队列中,95.5%的肺腺癌患者肿瘤组织中OCIAD2高表达,其表达升高与较差的生存率相关。功能研究表明,OCIAD2沉默会降低细胞迁移、侵袭和集落形成能力。基因集富集分析(GSEA)表明OCIAD2参与氧化磷酸化(OXPHOS)。随后,线粒体代谢分析表明OCIAD2损害OXPHOS功能,并伴随着代谢向糖酵解转变。这些发现表明,OCIAD2通过代谢重编程促进癌症进展,突出了OCIAD2作为肺腺癌潜在生物标志物和治疗靶点的作用。