RT Journal Article SR Electronic T1 A Novel Melatonergic Signature Predicts Reccurence Risk and Therapeutic Response in Breast Cancer Patients JF bioRxiv FD Cold Spring Harbor Laboratory SP 472753 DO 10.1101/472753 A1 Hoa Quynh Tran A1 Phuc Loi Luu A1 Van Thai Than A1 Declan Clarke A1 Hanh Ngoc Lam A1 Dinh Truong Nguyen A1 Kim Van Thi Le A1 Trung Viet Nguyen A1 Minh Thong Le A1 Xuan The Hoang A1 Phan Q. Duy A1 Huyen Tran A1 Minh Nam Nguyen YR 2018 UL http://biorxiv.org/content/early/2018/11/17/472753.abstract AB ASMT is a key determinant of the levels of released melatonin. Though 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 from thousands of patients and found that ASMT expression was significantly lower in breast cancer tumors relative to healthy tissue. Among cancer patients, those with greater expression had better relapse-free survival outcomes and longer metastasis-free survival times, and they also experienced longer periods before relapse or distance recurrence following tamoxifen treatment. Administration of melatonin, in combination with tamoxifen, further promoted cancer cell death by promoting apoptosis. Motivated by these results, we devised an ASMT gene signature that identifies low-risk cases with great accuracy. This signature was validated using both mRNA array and RNAseq datasets. Intriguingly, patients who are classified as high-risk 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. 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.