Xiong Luyang, Feng Yuchen, Hu Wei, Tan Jiahong, Li Shusheng, Wang Hongjie
Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2021 Jul 5;12:683173. doi: 10.3389/fgene.2021.683173. eCollection 2021.
Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer worldwide, and appropriate cancer biomarkers facilitate early diagnosis, treatment, and prognosis prediction in cancer management. However, an accurate biomarker for ccRCC is lacking. This study identified 356 differentially expressed genes in ccRCC tissues compared with normal kidney tissues by integrative analysis of eight ccRCC datasets. Enrichment analysis of the differentially expressed genes unveiled improved adaptation to hypoxia and metabolic reprogramming of the tumor cells. Aldehyde oxidase 1 () gene was identified as a biomarker for ccRCC among all the differentially expressed genes. ccRCC tissues expressed significantly lower than normal kidney tissues, which was further validated by immunohistochemistry at the protein level and The Cancer Genome Atlas (TCGA) data mining at the mRNA level. Higher expression predicted better overall survival in ccRCC patients. Furthermore, DNA copy number deletion and hypermethylation were negatively correlated with expression, which might be the potential mechanism for its dysregulation in ccRCC. Finally, we illustrated that the effect of as a tumor suppressor gene is not restricted to ccRCC but universally exists in many other cancer types. Hence, may act as a potential prognostic biomarker and therapeutic target for ccRCC.
透明细胞肾细胞癌（ccRCC）是全球最常见的肾癌，合适的癌症生物标志物有助于癌症管理中的早期诊断、治疗和预后预测。然而，目前缺乏一种针对ccRCC的准确生物标志物。本研究通过对八个ccRCC数据集的综合分析，确定了与正常肾组织相比，ccRCC组织中356个差异表达基因。对这些差异表达基因的富集分析揭示了肿瘤细胞对缺氧的适应性增强和代谢重编程。在所有差异表达基因中，醛氧化酶1（）基因被确定为ccRCC的生物标志物。ccRCC组织中该基因的表达明显低于正常肾组织，这在蛋白质水平通过免疫组织化学以及在mRNA水平通过癌症基因组图谱（TCGA）数据挖掘得到了进一步验证。较高的该基因表达预示着ccRCC患者更好的总生存期。此外，该基因的DNA拷贝数缺失和高甲基化与基因表达呈负相关，这可能是其在ccRCC中失调的潜在机制。最后，我们证明了该基因作为肿瘤抑制基因的作用不仅限于ccRCC，还普遍存在于许多其他癌症类型中。因此，该基因可能作为ccRCC的潜在预后生物标志物和治疗靶点。
