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High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy

Cancer Gene Therapy volume 26, pages 119–127 (2019)Cite this article

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Abstract

The SMAD family (SMAD1-9) was critically important for regulating cellular process through transforming growth factor-β signaling pathway, and contributed to carcinogenesis; however, their prognostic roles in acute myeloid leukemia (AML) remained unclear. This study collected 84 de novo AML patients treated with chemotherapy and 71 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Kaplan–Meier survival estimate indicated that among SMAD1-9, high SMAD3 and SMAD7 expression were both associated with poor event-free survival (EFS) and overall survival (OS; all P < 0.05) in AML patients undergoing chemotherapy; and high SMAD6 expression was associated with shorter EFS and OS (all P < 0.01) in patients underwent allo-HSCT. Multivariate analysis showed that only high SMAD7 expression had adverse effect on EFS and OS (P = 0.021, 0.026) independently. Furthermore, High SMAD3 and SMAD7 expressers had significantly shorter EFS and OS than low expressers (P = 0.006, 0.001). In AML patients who went through allo-HSCT, there were no significant differences for EFS and OS between patients with high and low-expression SMAD3 or SMAD7. Our study suggested that high expression of SMAD3 and SMAD7 predicted adverse prognosis in AML patients undergoing chemotherapy and SMAD7 was a better prognostic marker than SMAD3. Their prognosis impact may be overcome by allo-HSCT.

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Acknowledgements

We are grateful to the Cancer Genome Atlas (TCGA) database for their sharing of data.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81500118, 61501519), the China Postdoctoral Science Foundation funded project (Project No.2016M600443), PLAGH project of Medical Big Data (Project No.2016MBD-025), and Beijing Natural Science Foundation (7164310).

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Authors and Affiliations

  1. Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China

    Jilei Zhang, Xinpei Zhang, Gaoqi Zhang, Xinrui Yang, Siyuan Yang, Jing Wang, Kai Hu, Xiaoyan Ke & Lin Fu

  2. Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 7453100, China

    Lingxiu Zhang

  3. Peking University People’s Hospital, Beijing, 100044, China

    Haoran Cui

  4. Department of Stomatology, Peking University, Third Hospital, Beijing, 100191, China

    Zhihui Zhang

  5. Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, 100853, China

    Jinlong Shi

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  1. Jilei Zhang
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Zhang, J., Zhang, L., Cui, H. et al. High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy. Cancer Gene Ther 26, 119–127 (2019). https://doi.org/10.1038/s41417-018-0044-z

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