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Implications of NOVA1 suppression within the microenvironment of gastric cancer: association with immune cell dysregulation

 Eun Kyung Kim  ;  Sun Och Yoon  ;  Woon Yong Jung  ;  Hyunjoo Lee  ;  Youngran Kang  ;  You-Jin Jang  ;  Soon Won Hong  ;  Seung Ho Choi  ;  Woo Ick Yang 
 GASTRIC CANCER, Vol.20(3) : 438-447, 2017 
Journal Title
Issue Date
Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Female ; Forkhead Transcription Factors/metabolism ; Humans ; Kaplan-Meier Estimate ; Macrophages/metabolism ; Macrophages/pathology ; Male ; Middle Aged ; RNA-Binding Proteins/metabolism* ; Stomach Neoplasms/immunology* ; Stomach Neoplasms/mortality ; Stomach Neoplasms/pathology* ; Stromal Cells/metabolism ; Stromal Cells/pathology ; T-Lymphocytes/metabolism ; T-Lymphocytes/parasitology ; T-Lymphocytes, Regulatory/metabolism ; Tumor Microenvironment/immunology*
Gastric cancer ; Immune dysregulation ; Microenvironment ; Neuro-oncological ventral antigen 1
BACKGROUND: The neuronal splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in normal fibroblasts. Stromal spindle cells such as fibroblasts are major components of tissue inflammation and tertiary lymphoid structures within the microenvironment that contribute to the survival and growth of cancer cells. In the present study, we investigated changes of NOVA1 expression in tertiary lymphoid structures in early and advanced gastric cancer microenvironments in terms of tumor progression and immune regulation.

METHODS: Using immunohistochemistry, we analyzed NOVA1 expression in tumor cells, T cells, and stromal spindle cells as well as infiltrating densities of CD3+ T cells, forkhead box P3 positive (FOXP3+) regulatory T cells, CD68+ macrophages, CD163+ M2 macrophages, and myeloperoxidase-positive neutrophils in 396 surgically resected gastric cancer tissues.

RESULTS: Suppressed NOVA1 expression in tumor cells, T cells, and stromal spindle cells was closely related to decreased infiltration of FOXP3+ regulatory T cells, increased infiltration of CD68+ macrophages and CD163+ M2 macrophages, more advanced tumor stage, and inferior overall survival rate. In addition, low infiltration of CD3+ T cells and FOXP3+ regulatory T cells and high infiltration of CD68+ macrophages were associated with inferior overall survival. Specifically, weak NOVA1 expression in tumor cells was independently related to more advanced tumor stage and inferior overall survival.

CONCLUSIONS: NOVA1 suppression was frequently noted in the gastric cancer microenvironment, and attenuated NOVA1 expression in tumor cells was associated with tumor progression and poor prognosis. This finding seems to be related to immune dysfunction through changes in the immune cell composition of T cells and macrophages.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Kyung(김은경)
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Choi, Seung Ho(최승호) ORCID logo https://orcid.org/0000-0002-9872-3594
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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