Fu Lin, Fu Huaping, Qiao Jianlin, Pang Yifan, Xu Keman, Zhou Lei, Wu Qingyun, Li Zhenyu, Ke Xiaoyan, Xu Kailin, Shi Jinlong
Department of Hematology and Lymphoma Research Center, Third Hospital, Peking University, Beijing, China.
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Cancer Sci. 2017 Sep;108(9):1850-1857. doi: 10.1111/cas.13311. Epub 2017 Aug 20.
CPNE3, a member of a Ca -dependent phospholipid-binding protein family, was identified as a ligand of ERBB2 and has a more general role in carcinogenesis. Here, we identified the prognostic significance of CPNE3 expression in acute myeloid leukemia (AML) patients based on two datasets. In the first microarray dataset (n = 272), compared to low CPNE3 expression (CPNE3 ), high CPNE3 expression (CPNE3 ) was associated with adverse overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001). In the second independent group of AML patients (TCGA dataset, n = 179), CPNE3 was also associated with adverse OS and EFS (OS, P = 0.01; EFS, P = 0.036). Notably, among CPNE3 patients, those received allogenic hematopoietic cell transplantation (HCT) had longer OS and EFS than those with chemotherapy alone (allogeneic HCT, n = 40 vs chemotherapy, n = 46), but treatment modules played an insignificant role in the survival of CPNE3 patients (allogeneic HCT, n = 32 vs chemotherapy, n = 54). These results indicated that CPNE3 is an independent, adverse prognostic factor in AML and might guide treatment decisions towards allogeneic HCT. To understand its inherent mechanisms, we investigated genome-wide gene/microRNA expression signatures and cell signaling pathways associated with CPNE3 expression. In conclusion, CPNE3 is an adverse prognostic biomarker for AML. Its effect may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.
CPNE3是一种钙依赖性磷脂结合蛋白家族成员，被鉴定为ERBB2的配体，在致癌过程中具有更广泛的作用。在此，我们基于两个数据集确定了CPNE3表达在急性髓系白血病（AML）患者中的预后意义。在第一个微阵列数据集（n = 272）中，与低CPNE3表达（CPNE3低）相比，高CPNE3表达（CPNE3高）与不良总生存期（OS，P < 0.001）和无事件生存期（EFS，P < 0.001）相关。在第二组独立的AML患者（TCGA数据集，n = 179）中，CPNE3也与不良OS和EFS相关（OS，P = 0.01；EFS，P = 0.036）。值得注意的是，在CPNE3高患者中，接受异基因造血细胞移植（HCT）的患者比仅接受化疗的患者具有更长的OS和EFS（异基因HCT，n = 40 vs化疗，n = 46），但治疗模式在CPNE3低患者的生存中起的作用不显著（异基因HCT，n = 32 vs化疗，n = 54）。这些结果表明CPNE3是AML中一个独立的不良预后因素，可能指导针对异基因HCT的治疗决策。为了解其内在机制，我们研究了与CPNE3表达相关的全基因组基因/微小RNA表达特征和细胞信号通路。总之，CPNE3是AML的不良预后生物标志物。其作用可能归因于独特的全基因组基因/微小RNA表达及相关细胞信号通路。
