Experimental and clinicopathological analysis of HOXB9 in gastric cancer

Fumihiko Kato, Norihito Wada, Tetsu Hayashida, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Hirofumi Kawakubo, Hiroya Takeuchi, Yuukou Kitagawa

Research output: Contribution to journalArticle

Abstract

The association between homeobox (HOX)B9 expression and tumor malignancy was identified recently. It was reported that HOXB9 induced tumor angiogenesis, and associated with poor prognosis in patients with breast and colon cancer. On the other hand, regional lymph nodes are the most common site of tumor spread, and lymph node metastasis is a major prognostic factor in gastric cancer. It was hypothesized that HOXB9 promotes tumor lymphangiogenesis and induces tumor progression, invasion and metastasis in gastric cancer. The aim of the present study was to evaluate the correlation between HOXB9 expression, prognosis and clinicopathologic factors in patients with gastric cancer, and to assess the contribution of HOXB9 expression to tumor cell lymphangiogenesis in vitro. HOXB9 expression was evaluated by immunohistochemistry in resected tumor tissues from 58 patients with gastric cancer, and the association between prognosis and clinicopathologic factors was determined. HOXB9 gene was overexpressed in human gastric cancer TMK-1 cells and the effect of HOXB9 overexpression on the expression of vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor (R)-3 was determined. It was demonstrated that the depth of tumor invasion, the number of node metastases, lymphatic invasion and vascular invasion were significantly associated with HOXB9 expression. Overall survival was decreased in patients with HOXB9 expression. The mRNA expression of VEGF-D but not of VEGF-C and VEGFR-3 was increased in HOXB9-overexpressing TMK-1 cells compared with control cells. In conclusion, HOXB9 expression was positively correlated with gastric cancer progression and lymphangiogenesis marker expression. HOXB9 may be associated with lymphogenic metastasis.

Original languageEnglish
Pages (from-to)3097-3102
Number of pages6
JournalOncology Letters
Volume17
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

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Stomach Neoplasms
Lymphangiogenesis
Neoplasms
Vascular Endothelial Growth Factor D
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor C
Neoplasm Metastasis
Lymph Nodes
Lymphatic Metastasis
Homeobox Genes
Colonic Neoplasms
Blood Vessels
Immunohistochemistry
Breast Neoplasms
Messenger RNA
Survival
Genes

Keywords

  • Angiogenesis
  • Biomarker
  • Lymphangiogenesis
  • TMK-1
  • Vascular endothelial growth factor receptor-3
  • Vascular endothelial growth factor-C
  • Vascular endothelial growth factor-D

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Experimental and clinicopathological analysis of HOXB9 in gastric cancer. / Kato, Fumihiko; Wada, Norihito; Hayashida, Tetsu; Fukuda, Kazumasa; Nakamura, Rieko; Takahashi, Tsunehiro; Kawakubo, Hirofumi; Takeuchi, Hiroya; Kitagawa, Yuukou.

In: Oncology Letters, Vol. 17, No. 3, 01.03.2019, p. 3097-3102.

Research output: Contribution to journalArticle

Kato, Fumihiko ; Wada, Norihito ; Hayashida, Tetsu ; Fukuda, Kazumasa ; Nakamura, Rieko ; Takahashi, Tsunehiro ; Kawakubo, Hirofumi ; Takeuchi, Hiroya ; Kitagawa, Yuukou. / Experimental and clinicopathological analysis of HOXB9 in gastric cancer. In: Oncology Letters. 2019 ; Vol. 17, No. 3. pp. 3097-3102.
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AU - Nakamura, Rieko

AU - Takahashi, Tsunehiro

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AB - The association between homeobox (HOX)B9 expression and tumor malignancy was identified recently. It was reported that HOXB9 induced tumor angiogenesis, and associated with poor prognosis in patients with breast and colon cancer. On the other hand, regional lymph nodes are the most common site of tumor spread, and lymph node metastasis is a major prognostic factor in gastric cancer. It was hypothesized that HOXB9 promotes tumor lymphangiogenesis and induces tumor progression, invasion and metastasis in gastric cancer. The aim of the present study was to evaluate the correlation between HOXB9 expression, prognosis and clinicopathologic factors in patients with gastric cancer, and to assess the contribution of HOXB9 expression to tumor cell lymphangiogenesis in vitro. HOXB9 expression was evaluated by immunohistochemistry in resected tumor tissues from 58 patients with gastric cancer, and the association between prognosis and clinicopathologic factors was determined. HOXB9 gene was overexpressed in human gastric cancer TMK-1 cells and the effect of HOXB9 overexpression on the expression of vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor (R)-3 was determined. It was demonstrated that the depth of tumor invasion, the number of node metastases, lymphatic invasion and vascular invasion were significantly associated with HOXB9 expression. Overall survival was decreased in patients with HOXB9 expression. The mRNA expression of VEGF-D but not of VEGF-C and VEGFR-3 was increased in HOXB9-overexpressing TMK-1 cells compared with control cells. In conclusion, HOXB9 expression was positively correlated with gastric cancer progression and lymphangiogenesis marker expression. HOXB9 may be associated with lymphogenic metastasis.

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KW - Biomarker

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KW - Vascular endothelial growth factor receptor-3

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KW - Vascular endothelial growth factor-D

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