Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits
BackgroundPatients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.963411/full |
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| author | Yinjie Zhu Liancheng Fan Hanjing Zhu Yiming Gong Chenfei Chi Yanqing Wang Jiahua Pan Baijun Dong Wei Xue |
| author_facet | Yinjie Zhu Liancheng Fan Hanjing Zhu Yiming Gong Chenfei Chi Yanqing Wang Jiahua Pan Baijun Dong Wei Xue |
| author_sort | Yinjie Zhu |
| collection | DOAJ |
| description | BackgroundPatients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy.MethodsThe whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to identify predictive biomarkers for guiding treatment selection.ResultsComparing the transcriptome profiling of pre- and post-treatment LAPCa specimens, NHT and NCHT shared 1917 up- and 670 down-regulated DEGs at least 2-fold. Pathway enrichment analysis showed up-regulated pathways in response to NHT and NCHT were both enriched in cytokine receptor interaction pathways, and down-regulated pathways in response to NCHT were enriched in cell cycle pathways. By comprehensive transcriptome profiling of 64 baseline specimens, ten predictive markers were identified. We integrated them into the signature to evaluate the relative benefits of neoadjuvant therapy, which categorizes patients into two subgroups with relative bPFS benefits from either NHCT or NHT. In the high-score (≥ -95.798) group (n = 37), NCHT treatment led to significantly longer bPFS (P< 0.0001), with a clear and early separation of the Kaplan–Meier curves. In the low-score (< -95.798) group (n = 27), NHT also led to significantly longer bPFS (P=0.0025).ConclusionsIn this study, we proposed the first predictive transcriptomic signature might potentially guide the effective selection of neoadjuvant therapy in LAPCa and might provide precise guidance toward future personalized adjuvant therapy.Trial registrationThe study was approved by the Ethics Committee of Renji Hospital affiliated to Shanghai Jiao Tong University (Ky2019-087). |
| first_indexed | 2024-03-13T10:55:26Z |
| format | Article |
| id | doaj.art-8ffb4092d4e84c2d967975ae958b48a2 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T10:55:26Z |
| publishDate | 2023-05-01 |
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| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-8ffb4092d4e84c2d967975ae958b48a22023-05-17T04:53:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.963411963411Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefitsYinjie ZhuLiancheng FanHanjing ZhuYiming GongChenfei ChiYanqing WangJiahua PanBaijun DongWei XueBackgroundPatients with locally advanced prostate cancer (LAPCa) received docetaxel-based neoadjuvant chemo-hormonal therapy (NCHT) had better clinical outcomes after surgery compared to neoadjuvant hormonal therapy (NHT) groups, but not all patients experienced favorable clinical outcomes with NCHT, raising the necessity for potential biomarker assessment. The transcriptomic profiling offers a unique opportunity to interrogate the accurate response to NCHT and NHT treatment and to identify the predictive biomarkers for neoadjuvant therapy.MethodsThe whole transcriptomic profiling was performed on baseline biopsies and surgical tissue specimens from 64 patients with LAPCa at Renji Hospital between 2014 and 2018. Biochemical progression-free survival (bPFS)-based gene-by-treatment interaction effects were used to identify predictive biomarkers for guiding treatment selection.ResultsComparing the transcriptome profiling of pre- and post-treatment LAPCa specimens, NHT and NCHT shared 1917 up- and 670 down-regulated DEGs at least 2-fold. Pathway enrichment analysis showed up-regulated pathways in response to NHT and NCHT were both enriched in cytokine receptor interaction pathways, and down-regulated pathways in response to NCHT were enriched in cell cycle pathways. By comprehensive transcriptome profiling of 64 baseline specimens, ten predictive markers were identified. We integrated them into the signature to evaluate the relative benefits of neoadjuvant therapy, which categorizes patients into two subgroups with relative bPFS benefits from either NHCT or NHT. In the high-score (≥ -95.798) group (n = 37), NCHT treatment led to significantly longer bPFS (P< 0.0001), with a clear and early separation of the Kaplan–Meier curves. In the low-score (< -95.798) group (n = 27), NHT also led to significantly longer bPFS (P=0.0025).ConclusionsIn this study, we proposed the first predictive transcriptomic signature might potentially guide the effective selection of neoadjuvant therapy in LAPCa and might provide precise guidance toward future personalized adjuvant therapy.Trial registrationThe study was approved by the Ethics Committee of Renji Hospital affiliated to Shanghai Jiao Tong University (Ky2019-087).https://www.frontiersin.org/articles/10.3389/fonc.2023.963411/fullpredictive signaturelocally advanced prostate cancertranscriptomic profilingneoadjuvant chemo-hormonal therapyneoadjuvant hormonal therapy |
| spellingShingle | Yinjie Zhu Liancheng Fan Hanjing Zhu Yiming Gong Chenfei Chi Yanqing Wang Jiahua Pan Baijun Dong Wei Xue Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits Frontiers in Oncology predictive signature locally advanced prostate cancer transcriptomic profiling neoadjuvant chemo-hormonal therapy neoadjuvant hormonal therapy |
| title | Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits |
| title_full | Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits |
| title_fullStr | Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits |
| title_full_unstemmed | Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits |
| title_short | Transcriptomic signature defines two subtypes of locally advanced PCa with distinct neoadjuvant therapy benefits |
| title_sort | transcriptomic signature defines two subtypes of locally advanced pca with distinct neoadjuvant therapy benefits |
| topic | predictive signature locally advanced prostate cancer transcriptomic profiling neoadjuvant chemo-hormonal therapy neoadjuvant hormonal therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.963411/full |
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