Ontario Institute for Cancer Research, Toronto, Ontario, Canada. grainne.O'
Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Clin Cancer Res. 2020 Sep 15;26(18):4901-4910. doi: 10.1158/1078-0432.CCR-19-3724. Epub 2020 Mar 10.
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.
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 with the subtypes using gene expression profiling, hybridization (ISH) was explored.
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 ( = 0.02). In patients with basal-like tumors treated with modified FOLFIRINOX ( = 22), the progression rate was 60% compared with 15% in classical PDAC ( = 0.0002). Median OS in the intention-to-treat population ( = 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; = 0.0001). expression by RNA-seq highly correlated with the classifier ( < 0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariate analysis, GATA6 expression was prognostic ( = 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.
The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression..
确定基底样和经典亚型在晚期胰腺导管腺癌（PDAC）中的作用，并探索 GATA6 表达作为替代生物标志物。
在 COMPASS 试验中，接受晚期 PDAC 化疗的患者进行肿瘤活检进行 RNA 测序（RNA-seq）。根据接受的化疗方案，根据亚型和总体反应率（ORR）和总生存期（OS）进行分层。通过基因表达谱探索与亚型的相关性，通过杂交（ISH）探索 GATA6 与亚型的相关性。
2015 年 12 月至 2019 年 5 月，195 例患者（95%）有足够的组织进行 RNA-seq；39 例（20%）为基底样，156 例（80%）为经典型。157 例患者可获得 RECIST 反应数据；29 例基底样和 128 例经典型的 ORR 分别为 10%和 33%（ = 0.02）。在接受改良 FOLFIRINOX 治疗的基底样肿瘤患者中（ = 22），进展率为 60%，而经典 PDAC 为 15%（ = 0.0002）。意向治疗人群（ = 195）的中位 OS 为经典型 9.3 个月，基底样 PDAC 为 5.9 个月（HR，0.47；95%置信区间，0.32-0.69； = 0.0001）。通过 RNA-seq 进行的 GATA6 表达高度与分类器相关（ < 0.001），ISH 预测亚型的敏感性为 89%，特异性为 83%。在多变量分析中，GATA6 表达具有预后意义（ = 0.02）。在探索性分析中，基底样肿瘤可通过角蛋白 5 识别，其缺氧程度更高，并且富含 T 细胞浸润的基因表达特征。
基底样亚型对化疗耐药，可以通过 GATA6 表达与经典 PDAC 区分开来。
