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  • A Novel Signature Predicts Recurrence Risk and Therapeutic Response in Breast Cancer Patients

    Author(s)
    Tran, Quynh Hoa
    Than, Van Thai
    Luu, Phuc Loi
    Clarke, Declan
    Lam, Hanh Ngoc
    Nguyen, Thanh-Giang Tan
    Nguyen, Dinh Truong
    Duy, Phan Q
    Phung, Dung
    Nguyen, Minh Nam
    Griffith University Author(s)
    Phung, Dung T.
    Year published
    2021
    Metadata
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    Abstract
    Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles in 27 datasets on 7244 patients from 11 countries. We found that ASMT expression was significantly reduced in breast cancer tumors relative to healthy tissue. Among breast cancer patients, those with higher levels of ASMT expression had better relapse-free survival outcomes and longer metastasis-free ...
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    Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anti-cancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, we analyzed gene expression profiles in 27 datasets on 7244 patients from 11 countries. We found that ASMT expression was significantly reduced in breast cancer tumors relative to healthy tissue. Among breast cancer patients, those with higher levels of ASMT expression had better relapse-free survival outcomes and longer metastasis-free survival times. Following treatment with tamoxifen, patients with greater ASMT expression experienced longer periods before relapse or distance recurrence. Motivated by these results, we devised an ASMT gene signature that can correctly identify low-risk cases with a sensitivity and specificity of 0.997 and 0.916, respectively. This signature was robustly validated using 23 independent breast cancer mRNA array datasets from different platforms (consisting of 5800 patients) and an RNAseq dataset from TCGA (comprising 1096 patients). Intriguingly, patients who are classified as high-risk by the signature benefit from adjuvant chemotherapy, and those with grade II tumors who are classified as low-risk exhibit improved overall survival and distance relapse-free outcomes following endocrine therapy. Together, our findings more clearly elucidate the roles of ASMT, provide strategies for improving the efficacy of tamoxifen treatment, and help to identify those patients who may maximally benefit from adjuvant or endocrine therapies.
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    Journal Title
    International Journal of Cancer
    DOI
    https://doi.org/10.1002/ijc.33512
    Note
    This publication has been entered as an advanced online version in Griffith Research Online.
    Subject
    Oncology and Carcinogenesis
    ASMT
    breast cancer
    endocrine therapy
    gene signature
    recurrence risk prediction
    Publication URI
    http://hdl.handle.net/10072/402468
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    • Journal articles

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