4.6 Article

Accurate Prognosis Prediction of Pancreatic Ductal Adenocarcinoma Using Integrated Clinico-Genomic Data of Endoscopic Ultrasound-Guided Fine Needle Biopsy

Journal

CANCERS
Volume 13, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13112791

Keywords

targeted deep sequencing; pancreatic ductal adenocarcinoma; prognosis prediction; endoscopic ultrasound-guided fine needle core biopsy; clinico-genomic model

Categories

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1D1A1B03027859]
  2. National Research Foundation of Korea (NRF) - Korea government (MSIT) [2019R1C1C1008646]
  3. Dong-A ST
  4. Korean Gastroenterology Fund for Future Development
  5. National Research Foundation of Korea [2019R1C1C1008646] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study aimed to evaluate the feasibility of targeted sequencing using minimal specimens obtained from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Clinical prognostic factors and genetic alterations were identified and used to establish a clinico-genomic model for predicting patient outcomes in PDAC. Targeted deep sequencing on minimal specimens of PDAC was performed, and a clinico-genomic model for prognosis prediction was developed based on 20 single nucleotide variants and three copy number variations.
Simple Summary Around 10-20% of patients with pancreatic adenocarcinoma (PDAC) have a curative surgery, but most of them perform endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for the pathologic confirmation. The aim of our retrospective study was to evaluate the feasibility of targeted sequencing using EUS-FNB minimal specimens for the prognosis prediction of PDACs. We found some clinical factors and genetic alterations significantly related to the metastasis and overall survival, and established a clinico-genomic model by using both clinical parameters and genetic alterations to predict the prognosis of patients with PDACs. The aim of this study was to investigate the clinical utility of minimal specimens acquired from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and perform targeted deep sequencing as a prognosis prediction tool for pancreatic ductal adenocarcinoma (PDAC). A total of 116 specimens with pathologically confirmed PDAC via EUS-FNB were tested using CancerSCAN(R) panel for a customized targeted deep sequencing. Clinical prognostic factors significantly associated with survival in PDACs were as follows: stage, tumor mass size, tumor location, metastasis, chemotherapy, and initial CA19-9 level. A total of 114 patients (98.3%) had at least a single genetic alteration, and no mutations were detected in two patients, although they were qualified for the targeted deep sequencing. The frequencies of major gene mutations responsible for PDACs were KRAS 90%, CDKN2A 31%, TP53 77%, and SMAD4 29%. A somatic point mutation of NF1, copy number alteration of SMAD4, and loss-of-function of CDKN2A were significantly associated genetic factors for overall survival. Moreover, BRCA2 point mutation was related to liver metastasis. Finally, a clinico-genomic model was developed to estimate the prognosis of patients with PDAC based on clinical parameters and genetic alterations affecting survival in patients; 20 single nucleotide variants and three copy number variations were selected. Targeted deep sequencing on minimal specimens of PDACs was performed, and it was applied to establish a clinico-genomic model for prognosis prediction.

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