Yan Rui, Tan Heng-Wee, Cai Na-Li, Yu Le, Gao Yan, Xu Yan-Ming, Lau Andy T Y
The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, China.
Proteomes. 2025 Jun 3;13(2):22. doi: 10.3390/proteomes13020022.
Previously, we found that an uncharacterized protein CXorf38 is significantly downregulated in human ZIP8-knockout (KO) cells. Given that ZIP8 regulates essential micronutrients linked to diseases including cancer, this study aims to characterize CXorf38 and evaluate its role in lung adenocarcinoma. iTRAQ-based proteomics was previously used to identify the abundance of proteins in ZIP8-KO cells. Cell proliferation and colony formation assays were used to examine the function of CXorf38 by overexpressing the gene in lung adenocarcinoma cell lines. Kaplan-Meier survival analysis was used to assess the prognostic value of , while TCGA clinical database analysis was used to evaluate its expression in lung cancer tissues, particularly in smokers. Bioinformatics analyses (GO, KEGG, PPI, and ICI) were performed on -coexpressed genes derived from patients with lung cancer. CXorf38 overexpression suppressed lung cancer cell proliferation and colony formation, suggesting a tumor-suppressive role. Higher expression correlated with improved survival in patients with lung adenocarcinoma, but not in lung squamous cell carcinoma. Clinical data showed downregulation with lung cancer tissues of smokers, indicating a potential role in smoking-induced cancer progression and treatment. Functional analysis using bioinformatics linked CXorf38 to immune response regulation, suggesting involvement in the tumor immune microenvironment. Our study reveals for the first time that CXorf38 is a potential tumor suppressor, prognostic biomarker, and/or tumor immune regulator in lung adenocarcinoma-further research is warranted to explore its role in tumor immunity and its therapeutic potential.
此前，我们发现一种未被表征的蛋白质CXorf38在人ZIP8基因敲除（KO）细胞中显著下调。鉴于ZIP8调节与包括癌症在内的疾病相关的必需微量营养素，本研究旨在表征CXorf38并评估其在肺腺癌中的作用。基于iTRAQ的蛋白质组学先前被用于鉴定ZIP8-KO细胞中蛋白质的丰度。通过在肺腺癌细胞系中过表达该基因，利用细胞增殖和集落形成试验来检测CXorf38的功能。采用Kaplan-Meier生存分析评估其预后价值，并利用TCGA临床数据库分析评估其在肺癌组织中的表达，特别是在吸烟者中的表达。对来自肺癌患者的共表达基因进行生物信息学分析（GO、KEGG、PPI和ICI）。CXorf38过表达抑制肺癌细胞增殖和集落形成，提示其具有肿瘤抑制作用。较高的CXorf38表达与肺腺癌患者生存期改善相关，但与肺鳞癌患者无关。临床数据显示，吸烟者肺癌组织中CXorf38表达下调，表明其在吸烟诱导的癌症进展和治疗中可能发挥作用。利用生物信息学进行的功能分析将CXorf38与免疫反应调节联系起来，提示其参与肿瘤免疫微环境。我们的研究首次揭示，CXorf38在肺腺癌中是一种潜在的肿瘤抑制因子、预后生物标志物和/或肿瘤免疫调节因子，有必要进一步研究以探索其在肿瘤免疫中的作用及其治疗潜力。
