OncoTargets and Therapy (Nov 2020)
Identification and Validation of STAT6 as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia
Abstract
Wei Liu,1,2 Feiyue Zhu,3 Jiazhuo Yan,4 Yi Liu,1 Cong Chen,1 Kaixuan Zhang,1 Xielan Zhao,1 Jingyuan Chen5 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 2Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA; 3Department of Hematology, Loudi Central Hospital, Loudi, Hunan 417000, People’s Republic of China; 4Department of Gynaecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, People’s Republic of China; 5Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, Hunan 410011, People’s Republic of ChinaCorrespondence: Jingyuan ChenResearch Institute of Blood Lipid and Atherosclerosis, Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan 410011, People’s Republic of ChinaEmail [email protected]: Acute myeloid leukemia (AML) is one of the most common hematological diseases in adults. The overall survival rate remains unsatisfactory. It is urgent to identify potential prognostic biomarkers and develop new molecular therapeutic strategies for AML. Signal transducer and activator of transcription (STAT) is a family of genes that encode intracellular transcription factors. STATs are associated with leukemogenesis, cellular transformation, and cell cycle in AML.Methods: We used sequencing data and clinical data from The Cancer Genome Atlas (TCGA) and ONCOMINE to identify expression difference, gene variability and correlation as well as prognostic effects of STAT genes in AML patients. Then, we verified the expression difference of STAT6 between healthy control and AML patients and its prognostic impact in Gene Expression Omnibus (GEO) database and our own recruited cohort.Results: The mRNA level of STAT6 was increased in AML patients among TCGA, GEO and ONCOMINE public datasets and was found to be an independent risk factor of overall survival in all AML patients and patients who only received chemotherapy by multivariate analysis. In our study, STAT6 mRNA level was markedly up-regulated in AML patients (n=105) compared to healthy donor (n=39) (P=0.0435) as a validated cohort. Patients that only received chemotherapy in high STAT6 group showed significantly lower overall survival (OS) (P=0.0055).Conclusion: STAT6 expression was increased in AML patients. STAT6 was found to be an adverse prognosis factor in AML patients, especially those who only received chemotherapy treatments.Keywords: acute myeloid leukemia, STAT, prognosis, TCGA, GEO