Back to Search
Start Over
Aberration of ARID1A Is Associated With the Tumorigenesis and Prognosis of Sporadic Nonfunctional Pancreatic Neuroendocrine Tumors.
- Source :
-
Pancreas [Pancreas] 2020 Apr; Vol. 49 (4), pp. 514-523. - Publication Year :
- 2020
-
Abstract
- Objective: The genetic aberrations that underlie chromatin remodeling in sporadic nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) remain largely unknown. Here, we investigated the dysregulation of the switch/sucrose nonfermentable (SWI/SNF) component ARID1A and its correlation with clinicopathological features and prognosis.<br />Methods: We sequenced the exomes of sporadic NF-pNETs. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to determine messenger RNA level and protein expression.<br />Results: The sporadic NF-pNETs harbored 264 somatic mutations in 228 different genes, most commonly affecting the SWI/SNF components ARID1B (57.1%) and ARID1A (42.9%). The expression of ARID1A was remarkably downregulated in NF-pNETs and corresponding liver metastases compared with that in normal pancreatic islet tissue. Reduced expression of ARID1A was associated with malignant clinicopathological features (P < 0.05). The loss of ARID1A was related to a high Ki-67 index (P < 0.05). Patients with ARID1A-negative expression had a significantly worse overall survival rate than those with ARID1A-positive expression (P < 0.05). The ARID1A status was an independent predictor of overall survival, and a nomogram integrating ARID1A with clinicopathological features was proposed.<br />Conclusions: The loss of SWI/SNF components ARID1A may be associated with malignant behaviors and an unfavorable prognosis. Aberrations of ARID1A may contribute to tumorigenesis and metastasis in sporadic NF-pNETs.
- Subjects :
- Adult
China epidemiology
Chromatin Assembly and Disassembly genetics
DNA Mutational Analysis
DNA-Binding Proteins biosynthesis
Female
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms metabolism
Liver Neoplasms secondary
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Proteins biosynthesis
Neuroendocrine Tumors mortality
Neuroendocrine Tumors secondary
Neuroendocrine Tumors surgery
Nomograms
Pancreatic Neoplasms mortality
Pancreatic Neoplasms surgery
Prognosis
RNA, Messenger biosynthesis
RNA, Messenger genetics
RNA, Neoplasm biosynthesis
RNA, Neoplasm genetics
Real-Time Polymerase Chain Reaction
Survival Rate
Tissue Array Analysis
Transcription Factors biosynthesis
Exome Sequencing
DNA-Binding Proteins genetics
Neoplasm Proteins genetics
Neuroendocrine Tumors genetics
Pancreatic Neoplasms genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4828
- Volume :
- 49
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Pancreas
- Publication Type :
- Academic Journal
- Accession number :
- 32282764
- Full Text :
- https://doi.org/10.1097/MPA.0000000000001535