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

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)438-447
Number of pages10
JournalGastric Cancer
Volume20
Issue number3
DOIs
Publication statusPublished - 2017 May 1

Fingerprint

Stomach Neoplasms
Antigens
Macrophages
Neoplasms
T-Lymphocytes
Regulatory T-Lymphocytes
Stromal Cells
Tumor Microenvironment
Fibroblasts
Peroxidase
Neutrophils
Immunohistochemistry
Inflammation
Growth

Keywords

  • Gastric cancer
  • Immune dysregulation
  • Microenvironment
  • Neuro-oncological ventral antigen 1

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Implications of NOVA1 suppression within the microenvironment of gastric cancer : association with immune cell dysregulation. / Kim, Eun Kyung; Yoon, Sun Och; Jung, Woon Yong; Lee, Hyunjoo; Kang, Youngran; Jang, You-Jin; Hong, Soon Won; Choi, Seung Ho; Yang, Woo Ick.

In: Gastric Cancer, Vol. 20, No. 3, 01.05.2017, p. 438-447.

Research output: Contribution to journalArticle

Kim, Eun Kyung ; Yoon, Sun Och ; Jung, Woon Yong ; Lee, Hyunjoo ; Kang, Youngran ; Jang, You-Jin ; Hong, Soon Won ; Choi, Seung Ho ; Yang, Woo Ick. / Implications of NOVA1 suppression within the microenvironment of gastric cancer : association with immune cell dysregulation. In: Gastric Cancer. 2017 ; Vol. 20, No. 3. pp. 438-447.
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AU - Kim, Eun Kyung

AU - Yoon, Sun Och

AU - Jung, Woon Yong

AU - Lee, Hyunjoo

AU - Kang, Youngran

AU - Jang, You-Jin

AU - Hong, Soon Won

AU - Choi, Seung Ho

AU - Yang, Woo Ick

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N2 - 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.

AB - 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.

KW - Gastric cancer

KW - Immune dysregulation

KW - Microenvironment

KW - Neuro-oncological ventral antigen 1

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