title: NOVA1 inhibition by miR-146b-5p in the remnant tissue microenvironment defines occult residual disease after gastric cancer removal.
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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Woon Yong
authors.initials: WY
authors.lastname: Jung
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Korea.
authors.forename: Hyunjoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Youngran
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Hong
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000090682:Neuro-Oncological Ventral Antigen; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C000594513:NOVA1 protein, human; D000090682:Neuro-Oncological Ventral Antigen; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: NOVA1; hsa-microRNA-146b-5p; microenvironment; residual disease; stromal cells