Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

Sweta Sharma Saha; Lucy Gentles; Rachel Howarth; Stuart Rundle; Angela Ralte; Rachel O'Donnell; Nicola Curtin; Yvette Drew

doi:10.21203/rs.3.rs-2840508/v1

Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

Sweta Sharma Saha, Lucy Gentles, Rachel Howarth, Stuart Rundle, Angela Ralte, Rachel O'Donnell, Nicola Curtin, Yvette Drew

Research output: Working paper › Preprint

Abstract

Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.

Original language	English
Publisher	Research Square
DOIs	https://doi.org/10.21203/rs.3.rs-2840508/v1
Publication status	Published - 27 Apr 2023
Externally published	Yes

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10.21203/rs.3.rs-2840508/v1

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title = "Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers",

abstract = "Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.",

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T1 - Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

AU - Saha, Sweta Sharma

AU - Gentles, Lucy

AU - Howarth, Rachel

AU - Rundle, Stuart

AU - Ralte, Angela

AU - O'Donnell, Rachel

AU - Curtin, Nicola

AU - Drew, Yvette

PY - 2023/4/27

Y1 - 2023/4/27

N2 - Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.

AB - Neoadjuvant chemotherapy (NACT) has been known to induce genomic and transcriptomic alterations within tumours. Here, using transcriptome profiling along with histological analysis of pre and post NACT, we show temporal and disease site-specific differences (omentum, ovary and other sites) in high grade serous ovarian cancer (HGSOC) and their association with progression free and overall survival. We observed a significant reduction in genome instability signature score following NACT irrespective of disease site, which correlated with homologous recombination repair (HRR) function measured by RAD51 foci formation. However, increase in immuno-oncology and inflammation signatures was only observed in the omentum and not in the ovary post-NACT. DNA damage immune response (DDIR) along with HRR function were strongly associated with CD8+ T-cell infiltration within tumours. Our study provides transcriptomic and phenotypic data highlighting the heterogeneity in HGSOCs during the course of treatment and indicating how the tumour evolves in response to NACT.

UR - https://doi.org/10.21203/rs.3.rs-2840508/v1

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DO - 10.21203/rs.3.rs-2840508/v1

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BT - Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

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ER -

Temporal and disease-site specific transcriptional and phenotypic changes in response to neoadjuvant chemotherapy in high-grade serous ovarian cancers

Abstract

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