Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, Republic of Korea.
Interdisplinary Program of Genomic Science, Pusan National University, Yangsan, Republic of Korea.
Hematol Oncol. 2020 Aug;38(3):381-389. doi: 10.1002/hon.2728. Epub 2020 Mar 18.
Accurate prediction of malignancies is important in choosing therapeutic strategies. Although there are many genetic and cytogenetic prognostic factors for acute myeloid leukemia (AML), prognosis is difficult to predict because of the heterogeneity of AML. Prognostic factors, including messenger RNA (mRNA) expression, have been determined for other malignancies, but not for AML. A total of 402 patients from The Cancer Genome Atlas, GSE12417 (GPL96, 97), and GSE12417 (GPL570) were included in this study. In Kaplan-Meier curve analyses, high expression of family with sequence similarity 213 member A (FAM213A), which activates antioxidant proteins, was associated with worse prognosis of AML. Similar to the results of the survival curve, C-indices and area under the curve values were high. Current prognostic factors of AML, unlike those of other cancers, do not take mRNA expression into consideration. Thus, the development of mRNA-based prognostic factors would be beneficial for accurate prediction of the survival of AML patients. Additionally, in vivo validation using zebrafish revealed that fam213a is important for myelopoiesis at the developmental stage and is a negative regulator of the p53 tumor suppressor gene. The findings implicate fam213a as a novel prognostic factor for AML patients.
准确预测恶性肿瘤对于选择治疗策略非常重要。虽然急性髓细胞白血病 (AML) 有许多遗传和细胞遗传学预后因素，但由于 AML 的异质性，预后难以预测。已经确定了其他恶性肿瘤的预后因素，包括信使 RNA (mRNA) 表达，但 AML 则没有。本研究共纳入来自癌症基因组图谱、GSE12417（GPL96、97）和 GSE12417（GPL570）的 402 名患者。在 Kaplan-Meier 曲线分析中，激活抗氧化蛋白的家族与序列相似性 213 成员 A (FAM213A) 的高表达与 AML 的预后较差相关。与生存曲线的结果相似，C 指数和曲线下面积值较高。与其他癌症不同，AML 的当前预后因素不考虑 mRNA 表达。因此，开发基于 mRNA 的预后因素将有助于准确预测 AML 患者的生存情况。此外，使用斑马鱼进行的体内验证表明，fam213a 在发育阶段对髓系生成很重要，并且是 p53 肿瘤抑制基因的负调节剂。这些发现表明 fam213a 是 AML 患者的一个新的预后因素。
