我们应用超声内镜引导下的细针抽吸活检来进行细胞病理学诊断，并从原发性肿瘤中取样核酸，无论疾病阶段如何。在一项多中心前瞻性研究中纳入并随访了 397 名已确诊的胰腺腺癌患者。在内镜超声引导下细针抽吸活检获得的原发肿瘤材料中提取DNA和mRNA，分别使用靶向深度测序和RNAseq进行分析。KRAS突变的变异等位基因频率用于评估肿瘤细胞结构，范围从15到15。无论肿瘤处于什么阶段，所有细胞中的 20% 都是如此。转移性原发性肿瘤的分子谱与其他类型的肿瘤显着不同，TP53 突变的频率较高（p = 0.0002），RNF43 突变的频率较低，并且具有更多的基底样 mRNA 成分（p = 0.001）。与总生存期改善相关的分子标志物是：接受一线铂类化疗的患者中同源重组缺陷基因的突变（p = 0.025）和接受放化疗的局部晚期肿瘤患者中的野生型 TP53 基因突变（p = 0.01）。 GemPred 转录组谱与接受基于吉西他滨的一线治疗的局部晚期或转移性胰腺癌患者的总体生存率显着提高相关 (p = 0.019)。原发性胰腺肿瘤的基因组和转录组分析相结合使我们能够区分转移性肿瘤和其他肿瘤类型。我们的分子策略可能有助于预测基于铂类或吉西他滨的化疗以及放化疗的总体生存结果。国家杜癌症研究所 (BCB INCa_7294)、图卢兹 CHU、Inserm 和 Ligue Nationale Contre le Cancer (CIT 计划)。版权所有 © 2024。由 Elsevier B.V. 出版

We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage.397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively.The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019).The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy.Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).Copyright © 2024. Published by Elsevier B.V.