Cargando…

Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer

Estrogen receptor-positive (ER+) breast cancer (BC) is a common subtype of BC with a relatively good prognosis. However, recurrence and death from ER+ BC occur because of tumor heterogeneity. This study aimed to explore tumor heterogeneity using next-generation sequencing (NGS) and tumor-organoid mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yuhong, Gan, Yixiang, AiErken, NiJiati, Chen, Wei, Zhang, Shiwei, Ouyang, Jie, Zeng, Leli, Tang, Di
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9423951/
https://www.ncbi.nlm.nih.gov/pubmed/36046364
http://dx.doi.org/10.1155/2022/9390912
_version_ 1784778130113691648
author Liu, Yuhong
Gan, Yixiang
AiErken, NiJiati
Chen, Wei
Zhang, Shiwei
Ouyang, Jie
Zeng, Leli
Tang, Di
author_facet Liu, Yuhong
Gan, Yixiang
AiErken, NiJiati
Chen, Wei
Zhang, Shiwei
Ouyang, Jie
Zeng, Leli
Tang, Di
author_sort Liu, Yuhong
collection PubMed
description Estrogen receptor-positive (ER+) breast cancer (BC) is a common subtype of BC with a relatively good prognosis. However, recurrence and death from ER+ BC occur because of tumor heterogeneity. This study aimed to explore tumor heterogeneity using next-generation sequencing (NGS) and tumor-organoid models to promote BC precise therapy. We collected needle biopsy, surgical excision, and cerebrospinal fluid (CSF) samples to establish tumor organoids. We found that the histological characteristics of organoids were consistent with original lesions and recapitulated their heterogenicity. In addition, the NGS results showed that PIK3CA and TP53 genes had detrimental mutations. BAP1, RET, AXIN2, and PPP2R2A genes had mutations with unknown function. The score for homologous recombination deficiency (HRD) of genome was 56, indicating that the tumor was likely sensitive to PARPi. The mutant-allele tumor heterogeneity (MATH) value of the tumor genome was 68.03, indicating high tumor heterogeneity. At last, we performed a drug screening on organoids. The toxicity of different drugs toward BC organoids originated from needle biopsy and surgical excision was tested, respectively. The IC(50) values in the needle biopsy groups were paclitaxel 2.83 μM, carboplatin 61.47 μM, neratinib 0.8 μM, lapatinib >100 μM; in the surgical excision groups: trastuzumab >100 μM, docetaxel 0.036 μM, tamoxifen 20.54 μM, olaparib 5.478 μM, BYL719 < 0.1 μM. The toxicity data showed that the BC organoids could show dynamic characteristics of tumor progression and reflect the heterogeneity of BC. Our study demonstrates that the combined use of tumor organoids and NGS is a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributes to the development of personalized therapy.
format Online
Article
Text
id pubmed-9423951
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-94239512022-08-30 Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer Liu, Yuhong Gan, Yixiang AiErken, NiJiati Chen, Wei Zhang, Shiwei Ouyang, Jie Zeng, Leli Tang, Di J Oncol Research Article Estrogen receptor-positive (ER+) breast cancer (BC) is a common subtype of BC with a relatively good prognosis. However, recurrence and death from ER+ BC occur because of tumor heterogeneity. This study aimed to explore tumor heterogeneity using next-generation sequencing (NGS) and tumor-organoid models to promote BC precise therapy. We collected needle biopsy, surgical excision, and cerebrospinal fluid (CSF) samples to establish tumor organoids. We found that the histological characteristics of organoids were consistent with original lesions and recapitulated their heterogenicity. In addition, the NGS results showed that PIK3CA and TP53 genes had detrimental mutations. BAP1, RET, AXIN2, and PPP2R2A genes had mutations with unknown function. The score for homologous recombination deficiency (HRD) of genome was 56, indicating that the tumor was likely sensitive to PARPi. The mutant-allele tumor heterogeneity (MATH) value of the tumor genome was 68.03, indicating high tumor heterogeneity. At last, we performed a drug screening on organoids. The toxicity of different drugs toward BC organoids originated from needle biopsy and surgical excision was tested, respectively. The IC(50) values in the needle biopsy groups were paclitaxel 2.83 μM, carboplatin 61.47 μM, neratinib 0.8 μM, lapatinib >100 μM; in the surgical excision groups: trastuzumab >100 μM, docetaxel 0.036 μM, tamoxifen 20.54 μM, olaparib 5.478 μM, BYL719 < 0.1 μM. The toxicity data showed that the BC organoids could show dynamic characteristics of tumor progression and reflect the heterogeneity of BC. Our study demonstrates that the combined use of tumor organoids and NGS is a potential way to test tumor heterogeneity and predict drug response in ER + BC, which contributes to the development of personalized therapy. Hindawi 2022-08-22 /pmc/articles/PMC9423951/ /pubmed/36046364 http://dx.doi.org/10.1155/2022/9390912 Text en Copyright © 2022 Yuhong Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Yuhong
Gan, Yixiang
AiErken, NiJiati
Chen, Wei
Zhang, Shiwei
Ouyang, Jie
Zeng, Leli
Tang, Di
Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title_full Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title_fullStr Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title_full_unstemmed Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title_short Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer
title_sort combining organoid models with next-generation sequencing to reveal tumor heterogeneity and predict therapeutic response in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9423951/
https://www.ncbi.nlm.nih.gov/pubmed/36046364
http://dx.doi.org/10.1155/2022/9390912
work_keys_str_mv AT liuyuhong combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT ganyixiang combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT aierkennijiati combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT chenwei combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT zhangshiwei combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT ouyangjie combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT zengleli combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer
AT tangdi combiningorganoidmodelswithnextgenerationsequencingtorevealtumorheterogeneityandpredicttherapeuticresponseinbreastcancer