Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France.
Service de Gastroentérologie et Pancréatologie, Centre Hospitalier Universitaire de Toulouse-Rangueil (CHU), Toulouse, France.
EBioMedicine. 2024 Nov;109:105373. doi: 10.1016/j.ebiom.2024.105373. Epub 2024 Oct 8.
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).
我们应用内镜超声引导下细针抽吸活检术，对原发肿瘤进行细胞病理学诊断，并采集核酸，无论疾病阶段如何。
397 例经证实的胰腺腺癌患者纳入多中心前瞻性研究，并进行随访。从内镜超声引导下细针抽吸活检获得的原发肿瘤标本中提取 DNA 和 mRNA，分别采用靶向深度测序和 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的含量，所有细胞的范围为 15%至 20%，无论肿瘤阶段如何。转移性原发肿瘤的分子谱与其他类型的肿瘤明显不同，更频繁地出现 TP53 突变（p=0.0002），较少出现 RNF43 突变，并且具有更多的基底样 mRNA 成分（p=0.001）。与总体生存改善相关的分子标志物为：接受一线铂类化疗的同源重组缺陷基因突变患者（p=0.025）和接受放射化疗的局部进展期肿瘤患者中野生型 TP53 基因（p=0.01）。GemPred 转录组谱与接受吉西他滨为基础的一线治疗的局部晚期或转移性胰腺癌症患者的总体生存显著相关（p=0.019）。
原发胰腺肿瘤的基因组和转录组分析的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射化疗的总体生存结果。
法国国家癌症研究所（BCB INCa_7294）、图卢兹大学医疗中心、法国国家健康与医学研究院和法国抗癌联盟（CIT 计划）。
