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Oncol Lett. 2019 May;17(5):4647-4654. doi: 10.3892/ol.2019.10106. Epub 2019 Mar 4.

The stem cell-specific intermediate filament nestin missense variation p.A1199P is associated with pancreatic cancer.

Author information

1
Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo 173-0015, Japan.
2
Department of Genomics for Longevity and Health, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
3
Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
4
Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo 173-0015, Japan.
5
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
6
Department of Medical Informatics, Center for Information, Jichi Medical University, Tochigi 329-0498, Japan.
7
Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.

Abstract

The intermediate filament nestin is upregulated in stem/progenitor cells and cancers, and regulates cell proliferation, migration, invasion and stemness. The present study comparatively analyzed serial autopsies of Japanese patients (n=2,206; males, 1,225; females, 981; median, 80.7 years old; range, 33-104 years old) with malignant tumors of whole organs, with respect to the clinical information, and 5 single nucleotide polymorphisms of the nestin gene. p.A1199P associated with pancreatic cancer (odds ratio, 4.4; 95% confidence interval, 1.9-10.0, P=0.001) while it did not associate with malignant neoplasms in other organs. p.A1199P did not associate with precancerous lesions of the pancreas. Single nucleotide polymorphisms of nestin were not associated with sex, drinking, smoking, or body weight. In conclusion, the amino acid 1,199 of nestin is localized in the tail structure of the filament and polymerizes with other intermediate filament proteins. The present results suggest that missense variations of nestin affect pancreatic carcinogenesis in Japanese patients.

KEYWORDS:

intermediate filament; nestin; pancreatic cancer; single nucleotide polymorphism; stem cell

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