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Breast Cancer Research and Treatment

Erschienen in:

24.07.2019 | Epidemiology

Risk stratification of triple-negative breast cancer with core gene signatures associated with chemoresponse and prognosis

verfasst von: Eun-Kyu Kim, Ae Kyung Park, Eunyoung Ko, Woong-Yang Park, Kyung-Min Lee, Dong-Young Noh, Wonshik Han

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

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Abstract

Purpose

Neoadjuvant chemotherapy studies have consistently reported a strong correlation between pathologic response and long-term outcome in triple-negative breast cancer (TNBC). We aimed to define minimal gene signatures for predicting chemoresponse by a three-step approach and to further develop a risk-stratification method of TNBC.

Methods

The first step involved the detection of genes associated with resistance to docetaxel in eight TNBC cell lines, leading to identification of thousands of candidate genes. Through subsequent second and third step analyses with gene set enrichment analysis and survival analysis using public expression profiles, the candidate gene list was reduced to prognostic core gene signatures comprising ten or four genes.

Results

The prognostic core gene signatures include three up-regulated (CEBPD, MMP20, and WLS) and seven down-regulated genes (ASF1A, ASPSCR1, CHAF1B, DNMT1, GINS2, GOLGA2P5, and SKA1). We further develop a simple risk-stratification method based on expression profiles of the core genes. Relative expression values of the up-regulated and down-regulated core genes were averaged into two scores, Up and Down scores, respectively; then samples were stratified by a diagonal line in a xy plot of the Up and Down scores. Based on this method, the patients were successfully divided into subgroups with distinct chemoresponse and prognosis. The prognostic power of the method was validated in three independent public datasets containing 230, 141, and 117 TNBC patients with chemotherapy. In multivariable Cox regression analysis, the core gene signatures were significantly associated with prognosis independent of tumor stage and age at diagnosis. In meta-analysis, we found that five core genes (CEBPD, WLS, CHAF1B, GINS2, and SKA1) play opposing roles, either tumor promoter or suppressor, in TNBC and non-TNBC tumors respectively, depending on estrogen receptor status.

Conclusions

The results may provide a promising prognostic tool for predicting chemotherapy responders among TNBC patients prior to initiation of chemotherapeutic treatment.

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Titel: Risk stratification of triple-negative breast cancer with core gene signatures associated with chemoresponse and prognosis
verfasst von: Eun-Kyu Kim
Ae Kyung Park
Eunyoung Ko
Woong-Yang Park
Kyung-Min Lee
Dong-Young Noh
Wonshik Han
Publikationsdatum: 24.07.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05366-x

Springer Medizin

Risk stratification of triple-negative breast cancer with core gene signatures associated with chemoresponse and prognosis

Abstract

Purpose

Methods

Results

Conclusions

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Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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