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A novel signature predicts recurrence risk and therapeutic response in breast cancer patients

Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anticancer activity and prevents endocrine resistance in breast cancer, the role of ASMT in breast cancer progression remains unclear. In this retrospective study, w...

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Main Author: Tran, Quynh Hoa
Other Authors: Than, Van Thai
Format: Article
Language:English
Published: International Journal of Cancer 2021
Online Access:https://onlinelibrary.wiley.com/doi/10.1002/ijc.33512
https://dlib.phenikaa-uni.edu.vn/handle/PNK/1845
https://doi.org/10.1002/ijc.33512
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spelling oai:localhost:PNK-18452022-08-17T05:54:45Z A novel signature predicts recurrence risk and therapeutic response in breast cancer patients 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 Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anticancer 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 data sets 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 data sets from different platforms (consisting of 5800 patients) and an RNAseq data set 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. 2021-06-17T08:52:50Z 2021-06-17T08:52:50Z 2021 Article Working Paper https://onlinelibrary.wiley.com/doi/10.1002/ijc.33512 https://dlib.phenikaa-uni.edu.vn/handle/PNK/1845 https://doi.org/10.1002/ijc.33512 en International Journal of Cancer
institution Digital Phenikaa
collection Digital Phenikaa
language English
description Acetylserotonin O-methyltransferase (ASMT) is a key enzyme in the synthesis of melatonin. Although melatonin has been shown to exhibit anticancer 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 data sets 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 data sets from different platforms (consisting of 5800 patients) and an RNAseq data set 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.
author2 Than, Van Thai
author_facet Than, Van Thai
Tran, Quynh Hoa
format Article
author Tran, Quynh Hoa
spellingShingle Tran, Quynh Hoa
A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
author_sort Tran, Quynh Hoa
title A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
title_short A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
title_full A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
title_fullStr A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
title_full_unstemmed A novel signature predicts recurrence risk and therapeutic response in breast cancer patients
title_sort novel signature predicts recurrence risk and therapeutic response in breast cancer patients
publisher International Journal of Cancer
publishDate 2021
url https://onlinelibrary.wiley.com/doi/10.1002/ijc.33512
https://dlib.phenikaa-uni.edu.vn/handle/PNK/1845
https://doi.org/10.1002/ijc.33512
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score 8.887836

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