ArticleCancer2012
The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms.
Article in Cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.Military Medical Research · 2024Review
- The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms.Cancer science · 2022Article
- Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management-An Updated Review.Frontiers in oncology · 2020Review
- C-reactive protein (CRP) promotes malignant properties in pancreatic neuroendocrine neoplasms.Endocrine connections · 2019Article
- Role of Tumor-Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm.BMC cancer · 2018Article
- Minichromosome Maintenance Expression Defines Slow-Growing Gastroenteropancreatic Neuroendocrine Neoplasms.Translational oncology · 2016Article
- Expression pattern of neuronal intermediate filament α-internexin in anterior pituitary gland and related tumors.Pituitary · 2015Article
- Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology.Cellular and molecular gastroenterology and hepatology · 2015Review
- Stathmin in pancreatic neuroendocrine neoplasms: a marker of proliferation and PI3K signaling.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma.Epigenetics · 2014Article
- A mechanistic role for the chromatin modulator, NAP1L1, in pancreatic neuroendocrine neoplasm proliferation and metastases.Epigenetics & chromatin · 2014Article
- Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation.PloS one · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAlthough gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker.
methodsFunctional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses.
resultsIn BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P < .0001) and chromogranin A (r = 0.59; P < .0001). INA distinguished between primary tumors and metastases (P = .02), and its expression was correlated with tumor size, infiltration, and grade (P < .05).
conclusionsINA is a novel NEN biomarker, and its expression was associated with MAPK signaling and proliferation. In clinical samples, elevated INA was correlated with Ki-67 and identified malignancy. INA may provide additional biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior.
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