GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer
©2020 American Association for Cancer Research..
PURPOSE: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker.
EXPERIMENTAL DESIGN: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes using gene expression profiling, in situ hybridization (ISH) was explored.
RESULTS: Between December 2015 and May 2019, 195 patients (95%) had enough tissue for RNA-seq; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% versus 33%, respectively (P = 0.02). In patients with basal-like tumors treated with modified FOLFIRINOX (n = 22), the progression rate was 60% compared with 15% in classical PDAC (P = 0.0002). Median OS in the intention-to-treat population (n = 195) was 9.3 months for classical versus 5.9 months for basal-like PDAC (HR, 0.47; 95% confidence interval, 0.32-0.69; P = 0.0001). GATA6 expression by RNA-seq highly correlated with the classifier (P < 0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariate analysis, GATA6 expression was prognostic (P = 0.02). In exploratory analyses, basal-like tumors, could be identified by keratin 5, were more hypoxic and enriched for a T-cell-inflamed gene expression signature.
CONCLUSIONS: The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression.See related commentary by Collisson, p. 4715.
| Errataetall: |
CommentIn: Clin Cancer Res. 2020 Sep 15;26(18):4715-4716. - PMID 32661068 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 26(2020), 18 vom: 15. Sept., Seite 4901-4910 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
O'Kane, Grainne M [VerfasserIn] |
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| Links: |
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| Themen: |
04ZR38536J |
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| Anmerkungen: |
Date Completed 07.12.2021 Date Revised 13.06.2022 published: Print-Electronic CommentIn: Clin Cancer Res. 2020 Sep 15;26(18):4715-4716. - PMID 32661068 Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-19-3724 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM307450309 |
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| 245 | 1 | 0 | |a GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer |
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| 500 | |a CommentIn: Clin Cancer Res. 2020 Sep 15;26(18):4715-4716. - PMID 32661068 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2020 American Association for Cancer Research. | ||
| 520 | |a PURPOSE: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker | ||
| 520 | |a EXPERIMENTAL DESIGN: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes using gene expression profiling, in situ hybridization (ISH) was explored | ||
| 520 | |a RESULTS: Between December 2015 and May 2019, 195 patients (95%) had enough tissue for RNA-seq; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% versus 33%, respectively (P = 0.02). In patients with basal-like tumors treated with modified FOLFIRINOX (n = 22), the progression rate was 60% compared with 15% in classical PDAC (P = 0.0002). Median OS in the intention-to-treat population (n = 195) was 9.3 months for classical versus 5.9 months for basal-like PDAC (HR, 0.47; 95% confidence interval, 0.32-0.69; P = 0.0001). GATA6 expression by RNA-seq highly correlated with the classifier (P < 0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariate analysis, GATA6 expression was prognostic (P = 0.02). In exploratory analyses, basal-like tumors, could be identified by keratin 5, were more hypoxic and enriched for a T-cell-inflamed gene expression signature | ||
| 520 | |a CONCLUSIONS: The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression.See related commentary by Collisson, p. 4715 | ||
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