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Tumor copy number instability is a significant predictor for late recurrence after radical surgery of pancreatic ductal adenocarcinoma
- Source :
- Cancer Medicine, Cancer Medicine, Vol 9, Iss 20, Pp 7626-7636 (2020)
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- Objective Our study examined the association between molecular features and clinical results of pancreatic ductal adenocarcinoma (PDAC) patients, aiming to explore the genomic determinants of the recurrence and prognosis of PDAC after surgical removal. Methods This retrospective study analyzed 181 PDAC patients who received pancreatectomy and adjuvant chemotherapy, with 67 patients in the training set. An internal validation set of 48 patients and an external validation set of 66 patients were used to validate the result. Comprehensive genomic profiling was performed on formalin‐fixed paraffin‐embedded (FFPE) tumor specimens to determine genomic features using the designed cancer‐related gene panel based on next‐generation sequencing (NGS). Results Significant differences were identified between the late recurrence (LR) group and early recurrence (ER) group in tumor copy number instability (CNI) levels. Next, the utility of low CNI (the middle and lowest tertile) with regard to predicting LR was confirmed in the training, internal, and external validation sets. Further univariate and multivariate analyses revealed that CNI was an independent predictive and prognostic biomarker, and had higher predictive accuracy for LR than CA19‐9 level, pathological stage, tumor size, and age. In addition, CNI combined with lymph node (LN) metastasis status could provide a more accurate model for predicting LR of PDAC. Conclusion We discovered and validated the association between CNI and clinical outcome in 181 patients with resectable PDAC, demonstrating the utility of lower tumor CNI levels as biomarkers of postoperative LR and favorable prognosis. Moreover, the combination of CNI and LN metastasis status elevated the predictive accuracy and illuminated strategies for patient stratification.<br />We discovered and validated the association between copy number instability (CNI) and clinical outcome in 181 patients with resectable pancreatic ductal adenocarcinoma (PDAC), demonstrating the utility of lower tumor CNI levels as biomarkers of postoperative late recurrence and favorable prognosis. Moreover, the combination of CNI and lymph node metastasis status elevated the predictive accuracy and illuminated strategies for patient stratification.
- Subjects :
- 0301 basic medicine
Oncology
Male
Cancer Research
medicine.medical_treatment
Biopsy
Metastasis
0302 clinical medicine
late recurrence
Stage (cooking)
Lymph node
Original Research
Predictive marker
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Immunohistochemistry
Tumor Burden
medicine.anatomical_structure
030220 oncology & carcinogenesis
Pancreatectomy
Female
copy number instability
predictive marker
Carcinoma, Pancreatic Ductal
Adult
medicine.medical_specialty
DNA Copy Number Variations
pancreatic ductal adenocarcinoma
lcsh:RC254-282
03 medical and health sciences
Internal medicine
medicine
Biomarkers, Tumor
Humans
Radiology, Nuclear Medicine and imaging
Radical surgery
Pathological
Aged
Neoplasm Staging
business.industry
Clinical Cancer Research
Retrospective cohort study
medicine.disease
Survival Analysis
030104 developmental biology
ROC Curve
Mutation
Neoplasm Grading
Neoplasm Recurrence, Local
business
Subjects
Details
- Language :
- English
- ISSN :
- 20457634
- Volume :
- 9
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Cancer Medicine
- Accession number :
- edsair.doi.dedup.....8b919ee06e3f0d0cb637157373a23f1b