对原代胰腺腺癌的内窥镜超声引导的细针吸入材料的预测基因组和转录组分析：一项前瞻性多中心研究
Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study
影响因子:10.80000
分区:医学1区 Top / 医学：研究与实验1区
发表日期:2024 Nov
作者:
Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Selves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Barbara Bournet,
摘要
我们将内窥镜超声引导的细针吸入活检应用于细胞病理学诊断和来自原发性肿瘤的样品核酸。397例患有经过证明的胰腺腺癌的患者被包括在多中心前进研究中。从内窥镜超声引导的细针抽吸活检中获得的原发性肿瘤的材料中提取DNA和mRNA，并分别使用靶向深序列和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性，在所有细胞中均在所有细胞中范围为15至20％。转移性原发性肿瘤的分子谱与其他类型的肿瘤显着不同，更频繁地具有TP53突变（P = 0.0002），较少具有RNF43突变的频率，并且具有更多基础样的mRNA成分（P = 0.001）。与总体生存率改善相关的分子标记为：接受一线基于铂的化学疗法（P = 0.025）和野生型TP53基因的患者的同源重组缺乏基因的突变，患有局部晚期肿瘤的患者接受了无线电化学疗法（P = 0.01）。在局部晚期或转移性胰腺癌的患者中，宝石的转录组谱与接受基于吉西他滨的一线治疗（P = 0.019）的患者相关。基因组和转录组分析的组合使原发性胰腺肿瘤的结合使我们的转移性肿瘤与其他肿瘤类型区分开。我们的分子策略可以帮助预测基于铂或吉西他滨的化学疗法的总体生存结果，以及无线电化学疗法。
Abstract
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).