International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, 11031, Taiwan.
Funct Integr Genomics. 2022 Oct;22(5):1057-1072. doi: 10.1007/s10142-022-00883-3. Epub 2022 Jul 19.
As lung cancer remains the leading cause of cancer deaths globally, characterizing the tumor molecular profiles is crucial to tailoring treatments for individuals at advanced stages. Cancer cells exhibit strong dependence on iron for their proliferation, and several iron-regulatory proteins have been proposed as either oncogenes or tumor suppressive genes. This study aims to evaluate the prospective therapeutic and prognostic values of the sideroflexin (SFXN) gene family, whose functions involve mitochondrial iron metabolism, in lung adenocarcinoma (LUAD). Differential expression analysis using TIMER and UALCAN tools was first employed to compare SFXNs expression levels between normal and LUAD tissues. Next, SFXNs' prognostic values, biological significance, and potential as immunotherapy candidates were examined from GEPIA, cBioPortal, MetaCore, Cytoscape, and TIMER databases. It was found that all members of SFXN family, except SFXN3, were differentially expressed in LUAD compared to normal samples and within different stages of LUAD. Survival analysis then revealed SFXN1 to be related to worse overall survival outcome in patients with LUAD. Furthermore, several correlations between expression of SFXN1 and immune infiltration cells were discovered. To conclude, our study provides evidence of SFXN family gene's relevance to the prognosis and immunotherapeutic targets of LUAD.
由于肺癌仍然是全球癌症死亡的主要原因,因此对肿瘤分子谱进行特征描述对于为晚期患者量身定制治疗方案至关重要。癌细胞的增殖对铁有很强的依赖性,已经提出了几种铁调节蛋白作为癌基因或肿瘤抑制基因。本研究旨在评估铁载体蛋白(SFXN)基因家族在肺腺癌(LUAD)中的潜在治疗和预后价值,其功能涉及线粒体铁代谢。首先使用 TIMER 和 UALCAN 工具进行差异表达分析,比较 SFXNs 在正常和 LUAD 组织中的表达水平。接下来,从 GEPIA、cBioPortal、MetaCore、Cytoscape 和 TIMER 数据库中检查 SFXNs 的预后价值、生物学意义和作为免疫治疗候选物的潜力。结果发现,SFXN 家族的所有成员(SFXN3 除外)在 LUAD 与正常样本之间以及在 LUAD 的不同阶段均有差异表达。生存分析表明 SFXN1 与 LUAD 患者的总生存结局较差相关。此外,还发现了 SFXN1 表达与免疫浸润细胞之间的几种相关性。总之,本研究为 SFXN 家族基因与 LUAD 的预后和免疫治疗靶点相关提供了证据。