Michael Guenther, Sai Agash Surendran, Lea Margareta Steinke, Iduna Liou, Melanie Alexandra Palm, Volker Heinemann, Michael Haas, Stefan Boeck, Steffen Ormanns
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This study aimed to determine the prognostic or predictive impact of both subtyping marker panels in two large cohorts of advanced and resected pancreatic ductal adenocarcinoma (PDAC) patients.</p><p><strong>Methods: </strong>Transcriptional subtypes were determined by combining the expression of KRT81/HNF1A or assessing GATA6 expression alone by IHC in samples of two independent PDAC patient cohorts (advanced PDAC <i>n</i> = 139 and resected PDAC <i>n</i> = 411) as well as in 57 matched primary tumors and their corresponding metastases. RNAseq-based expression data of 316 resected PDAC patients was analyzed for validation.</p><p><strong>Results: </strong>Transcriptional subtypes widely overlapped in both marker panels (χ<sup>2</sup><i>p</i> < 0.001) but switched during disease progression in up to 31.6% of patients. They had a modest impact on the patients' prognosis in both cohorts, with longer overall survival (OS) for patients with KRT81-/HNF1A+ or GATA6+ tumors but better progression-free survival (PFS) and disease-free survival (DFS) in patients with KRT81+/GATA6- tumors treated with palliative or adjuvant gemcitabine-based chemotherapy. RNAseq expression data confirmed the findings.</p><p><strong>Conclusions: </strong>Transcriptional subtypes have differential responses to palliative and adjuvant gemcitabine-based chemotherapy and may change during disease progression. 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引用次数: 0
摘要
背景：基于标志基因表达的胰腺导管腺癌（PDAC）转录亚型可能具有预后意义和潜在的预测功能。两种最常用的亚型标记评估KRT81和HNF1A的联合表达或GATA6的单独表达，可以通过免疫组化（IHC）检测。本研究旨在确定两种亚型标记组在两组晚期和切除胰腺导管腺癌（PDAC）患者中的预后或预测影响。方法：在两个独立的PDAC患者队列（晚期PDAC n = 139和切除PDAC n = 411）以及57个匹配的原发肿瘤及其相应的转移瘤样本中，通过结合KRT81/HNF1A的表达或单独通过免疫组化评估GATA6的表达来确定转录亚型。分析316例PDAC切除患者基于rnaseq的表达数据进行验证。结果：转录亚型在两个标记组中广泛重叠（χ2p < 0.001），但在高达31.6%的患者中，转录亚型在疾病进展过程中发生切换。在两个队列中，它们对患者的预后都有适度的影响，KRT81-/HNF1A+或GATA6+肿瘤患者的总生存期（OS）更长，但接受姑息性或辅助性吉西他滨化疗的KRT81+/GATA6-肿瘤患者的无进展生存期（PFS）和无病生存期（DFS）更好。RNAseq表达数据证实了这一发现。结论：转录亚型对姑息性和辅助性吉西他滨化疗有不同的反应，并可能在疾病进展过程中发生变化。两种采用的亚型标记面板是相同的，可用于告知临床治疗决策。
The Prognostic, Predictive and Clinicopathological Implications of KRT81/HNF1A- and GATA6-Based Transcriptional Subtyping in Pancreatic Cancer.
Background: Transcriptional subtypes of pancreatic ductal adenocarcinoma (PDAC) based on the expression of hallmark genes may have prognostic implications and potential predictive functions. The two most employed subtyping markers assess the combined expression of KRT81 and HNF1A or of GATA6 alone, which can be detected by immunohistochemistry (IHC). This study aimed to determine the prognostic or predictive impact of both subtyping marker panels in two large cohorts of advanced and resected pancreatic ductal adenocarcinoma (PDAC) patients.
Methods: Transcriptional subtypes were determined by combining the expression of KRT81/HNF1A or assessing GATA6 expression alone by IHC in samples of two independent PDAC patient cohorts (advanced PDAC n = 139 and resected PDAC n = 411) as well as in 57 matched primary tumors and their corresponding metastases. RNAseq-based expression data of 316 resected PDAC patients was analyzed for validation.
Results: Transcriptional subtypes widely overlapped in both marker panels (χ2p < 0.001) but switched during disease progression in up to 31.6% of patients. They had a modest impact on the patients' prognosis in both cohorts, with longer overall survival (OS) for patients with KRT81-/HNF1A+ or GATA6+ tumors but better progression-free survival (PFS) and disease-free survival (DFS) in patients with KRT81+/GATA6- tumors treated with palliative or adjuvant gemcitabine-based chemotherapy. RNAseq expression data confirmed the findings.
Conclusions: Transcriptional subtypes have differential responses to palliative and adjuvant gemcitabine-based chemotherapy and may change during disease progression. Both employed subtyping marker panels are equivalent and may be used to inform clinical therapy decisions.
BiomoleculesBiochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍：
Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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