Dataset Information

Identification and Validation of STAT6 as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia.

ABSTRACT: Background: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.

SUBMITTER: Liu W

PROVIDER: S-EPMC7648156 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification and Validation of <i>STAT6</i> as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia.

Liu Wei W Zhu Feiyue F Yan Jiazhuo J Liu Yi Y Chen Cong C Zhang Kaixuan K Zhao Xielan X Chen Jingyuan J

OncoTargets and therapy 20201102

<h4>Background</h4>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.<h4>Methods< ...[more]

PMID: 33173308

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Project description:Although the implication of BCL3 has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic of BCL3 expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detect BCL3 expression level. BCL3 mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls (P = 0.0015). BCL3 was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes (P = 0.014). ROC analysis demonstrated that BCL3 could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of low BCL3 expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 (P = 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 (P = 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed that BCL3low patients had a remarkably higher frequency of t (8;21) abnormality (P = 0.0047) and lower frequency of normal karyotype (P = 0.0059) than BCL3high patients. BCL3high patients showed a significantly higher frequency of FLT3-ITD mutation (P = 0.028) and lower frequency of C-Kit mutation (P = 0.0232) than BCL3low patients. Although there were no significant differences in complete remission and overall survival between BCL3low and BCL3high groups, patients with high BCL3 expression markedly shorter overall survival (OS, P = 0.049), relapse-free survival (RFS, P = 0.027) and disease-free survival (DFS, P = 0.042) in M2 AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate (P = 0.0317) after the second induction treatment than patients with BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.

Dataset Information

Identification and Validation of STAT6 as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia.

Publications

Identification and Validation of <i>STAT6</i> as a Prognostic and Predictive Biomarker in Acute Myeloid Leukemia.

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