Abstract
Simple SummaryAround 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® 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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States of America [1], and the fifth leading cause in Korea [2]
Survival data was obtained from the hospital database, and information on mortality was collected via telephone calls in cases of loss to follow-up
Univariate cox regression analysis indicated that pancreatic ductal adenocarcinoma (PDAC) patients with somatic mutations in NF1 (3.35 vs. 9.63 months; HR = 6.21; p = 0.0061) showed worse prognosis (Figure 5A), and copy number variations (CNVs) deletion of SMAD4 (22.2 vs. 8.50 months; HR = 0.40; p = 0.0367) was related to longer survival (Figure 5B)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the United States of America [1], and the fifth leading cause in Korea [2]. The five year overall survival (OS) rate for PDAC is approximately 7%, which is attributed to the typically advanced stage at diagnosis, combined with the lack of effective systemic chemotherapy available [3]. Predicting the prognosis and identifying patients who could benefit from specific therapies could improve the OS of patients with pancreatic cancer. The factors responsible for the survival of patients with PDAC are poorly understood. The favorable prognostic factors of PDAC are primarily clinical factors, such as early disease stage, negative resection margins, and negative lymph nodes [4]. Current clinical prognostic factors produce limitations in predicting the prognosis of PDAC and selecting suitable patients for specific systemic chemotherapy regimens
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