Department of Hematology, The First People's Hospital of Yongkang, Affiliated to Hangzhou Medical College, No. 599, Jinshan West Road, Yongkang, Jinhua City, Zhejiang Province, 321300, People's Republic of China.
Mol Biotechnol. 2023 Nov;65(11):1898-1912. doi: 10.1007/s12033-023-00704-3. Epub 2023 Mar 6.
The advantage of an increasing amount of bioinformatics data on leukemias intrigued us to explore the hot-spot mutation profiles and investigate the implications of those hot-spot mutations in patient survival. We retrieved somatic mutations and their distribution in protein domains through data analysis of The Cancer Genome Atlas and cBioPortal databases. After determining differentially expressed mutant genes related to leukemia, we further conducted principal component analysis and single-factor Cox regression analyses. Moreover, survival analysis was performed for the obtained candidate genes, followed by a multi-factor Cox proportional hazard model method for the impacts of the candidate genes on the survival and prognosis of patients with leukemia. At last, the signaling pathways involved in leukemia were investigated by gene set enrichment analysis. There were 223 somatic missense mutation hot-spots identified with pertinence to leukemia, which were distributed in 41 genes. Differential expression in leukemia was witnessed in 39 genes. We found a close correlation between seven genes and the prognosis of leukemia patients, among which, three genes could significantly influence the survival rate. In addition, among these three genes, CD74 and P2RY8 were highlighted due to close pertinence with survival conditions of leukemia patients. Finally, data suggested that B cell receptor, Hedgehog, and TGF-beta signaling pathways were enriched in low-hazard patients. In conclusion, these data underline the involvement of hot-spot mutations of CD74 and P2RY8 genes in survival status of leukemia patients, highlighting their as novel therapeutic targets or prognostic indicators for leukemia patients. Summary of Graphical Abstract: We identified 223 leukemia-associated somatic missense mutation hotspots concentrated in 41 different genes from 2297 leukemia patients in the TCGA database. Differential analysis of leukemic and normal samples from the TCGA and GTEx databases revealed that 39 of these 41 genes showed significant differential expression in leukemia. These 39 genes were subjected to PCA analysis, univariate Cox analysis, survival analysis, multivariate Cox regression analysis, GSEA pathway enrichment analysis, and then the association with leukemia survival prognosis and related pathways were investigated.
我们对白血病中越来越多的生物信息学数据的优势感到好奇，因此我们探索了热点突变谱，并研究了这些热点突变对患者生存的影响。我们通过对癌症基因组图谱（TCGA）和 cBioPortal 数据库的数据进行分析，检索了体细胞突变及其在蛋白质结构域中的分布。在确定与白血病相关的差异表达突变基因后，我们进一步进行了主成分分析和单因素 Cox 回归分析。此外，对获得的候选基因进行了生存分析，然后使用多因素 Cox 比例风险模型方法评估候选基因对白血病患者生存和预后的影响。最后，通过基因集富集分析研究了涉及白血病的信号通路。在与白血病相关的 223 个体细胞错义突变热点中，有 41 个基因发生突变，涉及 41 个基因。在白血病中发现 39 个基因差异表达。我们发现，在 7 个基因与白血病患者的预后密切相关，其中 3 个基因可以显著影响生存率。此外，在这 3 个基因中，CD74 和 P2RY8 基因由于与白血病患者的生存状况密切相关，因此更为突出。最后，数据表明，B 细胞受体、Hedgehog 和 TGF-β信号通路在低风险患者中得到了富集。总之，这些数据强调了 CD74 和 P2RY8 基因热点突变在白血病患者生存状态中的作用，为白血病患者的治疗靶点或预后标志物提供了新的依据。
