Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-10-08 DOI:10.1016/j.ebiom.2024.105373

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

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Abstract

Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage.

Methods: 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.

Findings: 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).

Interpretation: 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.

Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

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内镜超声引导下原发性胰腺腺癌细针穿刺材料的基因组和转录组预测分析：一项前瞻性多中心研究。

背景：我们应用内镜超声引导下细针穿刺活检术对原发性肿瘤进行细胞病理学诊断和核酸采样，而不受疾病分期的限制。方法：在一项多中心前瞻性研究中，纳入并随访了397例经证实的胰腺腺癌患者。从内镜超声引导下细针穿刺活检获得的原发肿瘤材料中提取DNA和mRNA，并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可用于评估肿瘤的细胞性，无论肿瘤分期如何，所有细胞的KRAS突变等位基因频率在15%至20%之间。转移性原发性肿瘤的分子特征与其他类型的肿瘤有明显不同，更常见的是TP53突变（p = 0.0002），较少的是RNF43突变，并具有更多的基底样mRNA成分（p = 0.001）。与总生存率提高相关的分子标记是：接受一线铂类化疗的患者同源重组缺陷基因突变（p = 0.025），以及接受放射化疗的局部晚期肿瘤患者野生型 TP53 基因（p = 0.01）。在接受吉西他滨一线治疗的局部晚期或转移性胰腺癌患者中，GemPred转录组特征与总生存率显著提高相关（p = 0.019）：原发性胰腺肿瘤的基因组和转录组分析相结合，使我们能够将转移性肿瘤与其他类型的肿瘤区分开来。我们的分子策略可能有助于预测以铂或吉西他滨为基础的化疗以及放射化疗的总体生存结果：国家癌症研究所（BCB INCa_7294）、图卢兹中央医院、Inserm和国家抗癌联盟（CIT计划）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.