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NOVA1 inhibition by miR-146b-5p in the remnant tissue microenvironment defines occult residual disease after gastric cancer removal

Authors
 Sun Och Yoon  ;  Eun Kyung Kim  ;  Mira Lee  ;  Woon Yong Jung  ;  Hyunjoo Lee  ;  Youngran Kang  ;  You-Jin Jang  ;  Soon Won Hong  ;  Seung Ho Choi  ;  Woo Ick Yang 
Citation
 Oncotarget, Vol.7(3) : 2475-2495, 2016 
Journal Title
 Oncotarget 
Issue Date
2016
Abstract
Occult residual disease in remnant tissues could be the cause of tumor relapse. To identify signal molecules and target cells that may be indicative of occult residual disease within a remnant microenvironment, proximal resection margin tissues of gastric cancers were used, as these correspond to the nearest remnant tissues after gastrectomy. Increased miR-146b-5p in the remnant microenvironment was determined to be a strong risk factor for tumor relapse and poor survival rate. NOVA1, a target gene of miR-146b-5p, was decreased in remnant tissues of patients with a poor prognosis. NOVA1 was enriched in stromal spindle cells such as fibroblasts within normal tissues. In non-neoplastic inflammation, such as gastritis, NOVA1 was highly enriched in T lymphocytes and stromal spindle cells, while expression of this protein was frequently decreased in those types of cells within gastric cancer tissues. Particularly, decreased NOVA1 in T cells within the gastric cancer tissues was correlated with decreased FOXP3-positive regulatory T cells and was associated with poor patient prognosis. In vitro analysis showed that the NOVA1 gene was inhibited by miR-146b-5p. In immune cells as well as stromal spindle cells, decreased NOVA1, possibly inhibited by miR-146b-5p, is a candidate biomarker predicting poor prognosis of gastric cancer patients and is also a biomarker of occult residual disease in remnant tissues after gastric cancer removal.
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DOI
10.18632/oncotarget.6542
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
김은경(Kim, Eun Kyung)
양우익(Yang, Woo Ick) ORCID logo https://orcid.org/0000-0002-6084-5019
윤선옥(Yoon, Sun Och) ORCID logo https://orcid.org/0000-0002-5115-1402
최승호(Choi, Seung Ho)
홍순원(Hong, Soon Won) ORCID logo https://orcid.org/0000-0002-0324-2414
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/155770
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