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  6. Predictive Genomic And Transcriptomic Analysis On Endoscopic Ultrasound-guided Fine Needle Aspiration Materials From Primary Pancreatic Adenocarcinoma: A Prospective Multicentre Study

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

Rémy Nicolle1, Cindy Canivet2, Laurent Palazzo3

  • 1Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, Paris F-75018, France.

Ebiomedicine
|October 9, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Genomic and transcriptomic analysis of pancreatic tumors can distinguish metastatic from non-metastatic types. This molecular approach aids in predicting patient survival with specific chemotherapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics
Keywords:
Pancreatic cancerPredictive medicineRNA sequencingTargeted DNA deep sequencing

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Background:

  • Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is used for cytopathological diagnosis and nucleic acid sampling of primary tumors.
  • Pancreatic adenocarcinoma diagnosis and molecular profiling are crucial for treatment stratification.

Purpose of the Study:

  • To investigate the utility of combined genomic and transcriptomic analyses in characterizing pancreatic tumors.
  • To identify molecular markers that differentiate metastatic from non-metastatic pancreatic tumors.
  • To predict patient survival outcomes based on molecular profiles and treatment regimens.

Main Methods:

  • A multicenter prospective study included 397 patients with pancreatic adenocarcinoma.
  • DNA and mRNA were extracted from primary tumors via EUS-FNA.
  • Targeted deep sequencing and RNA sequencing (RNAseq) were employed for molecular analysis.

Main Results:

  • KRAS mutation variant allele frequency indicated tumor cellularity (15–20%).
  • Metastatic tumors showed distinct molecular profiles, with increased TP53 mutations and a basal-like mRNA component.
  • Molecular markers, including homologous recombination deficiency gene mutations and wild-type TP53, predicted improved survival in specific patient groups.
  • The GemPred transcriptomic profile correlated with better overall survival in patients receiving gemcitabine-based therapy.

Conclusions:

  • Combined genomic and transcriptomic analyses effectively distinguish metastatic pancreatic tumors.
  • This molecular strategy can aid in predicting survival outcomes for platinum-based chemotherapy, gemcitabine-based chemotherapy, and radio-chemotherapy.
Translational medicine