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Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their tran...

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Autores principales: Zhang, Kaiyang, Erkan, Erdogan Pekcan, Jamalzadeh, Sanaz, Dai, Jun, Andersson, Noora, Kaipio, Katja, Lamminen, Tarja, Mansuri, Naziha, Huhtinen, Kaisa, Carpén, Olli, Hietanen, Sakari, Oikkonen, Jaana, Hynninen, Johanna, Virtanen, Anni, Häkkinen, Antti, Hautaniemi, Sampsa, Vähärautio, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865800/
https://www.ncbi.nlm.nih.gov/pubmed/35196078
http://dx.doi.org/10.1126/sciadv.abm1831
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author Zhang, Kaiyang
Erkan, Erdogan Pekcan
Jamalzadeh, Sanaz
Dai, Jun
Andersson, Noora
Kaipio, Katja
Lamminen, Tarja
Mansuri, Naziha
Huhtinen, Kaisa
Carpén, Olli
Hietanen, Sakari
Oikkonen, Jaana
Hynninen, Johanna
Virtanen, Anni
Häkkinen, Antti
Hautaniemi, Sampsa
Vähärautio, Anna
author_facet Zhang, Kaiyang
Erkan, Erdogan Pekcan
Jamalzadeh, Sanaz
Dai, Jun
Andersson, Noora
Kaipio, Katja
Lamminen, Tarja
Mansuri, Naziha
Huhtinen, Kaisa
Carpén, Olli
Hietanen, Sakari
Oikkonen, Jaana
Hynninen, Johanna
Virtanen, Anni
Häkkinen, Antti
Hautaniemi, Sampsa
Vähärautio, Anna
author_sort Zhang, Kaiyang
collection PubMed
description Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer–associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance.
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spelling pubmed-88658002022-03-10 Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer Zhang, Kaiyang Erkan, Erdogan Pekcan Jamalzadeh, Sanaz Dai, Jun Andersson, Noora Kaipio, Katja Lamminen, Tarja Mansuri, Naziha Huhtinen, Kaisa Carpén, Olli Hietanen, Sakari Oikkonen, Jaana Hynninen, Johanna Virtanen, Anni Häkkinen, Antti Hautaniemi, Sampsa Vähärautio, Anna Sci Adv Biomedicine and Life Sciences Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer–associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance. American Association for the Advancement of Science 2022-02-23 /pmc/articles/PMC8865800/ /pubmed/35196078 http://dx.doi.org/10.1126/sciadv.abm1831 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Zhang, Kaiyang
Erkan, Erdogan Pekcan
Jamalzadeh, Sanaz
Dai, Jun
Andersson, Noora
Kaipio, Katja
Lamminen, Tarja
Mansuri, Naziha
Huhtinen, Kaisa
Carpén, Olli
Hietanen, Sakari
Oikkonen, Jaana
Hynninen, Johanna
Virtanen, Anni
Häkkinen, Antti
Hautaniemi, Sampsa
Vähärautio, Anna
Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title_full Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title_fullStr Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title_full_unstemmed Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title_short Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
title_sort longitudinal single-cell rna-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865800/
https://www.ncbi.nlm.nih.gov/pubmed/35196078
http://dx.doi.org/10.1126/sciadv.abm1831
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