TY - JOUR
T1 - Experimental and clinicopathological analysis of HOXB9 in gastric cancer
AU - Kato, Fumihiko
AU - Wada, Norihito
AU - Hayashida, Tetsu
AU - Fukuda, Kazumasa
AU - Nakamura, Rieko
AU - Takahashi, Tsunehiro
AU - Kawakubo, Hirofumi
AU - Takeuchi, Hiroya
AU - Kitagawa, Yuko
N1 - Funding Information:
The present work was supported by a JSPS KAKENHI Grant-in-Aid for Young Scientists (B) (grant no. 26861103) and a Grant-in-Aid for Scientific Research (C) (grant nos. 22591469 and 25462037).
Publisher Copyright:
© 2019, Spandidos Publications. All rights reserved.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
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.
KW - Angiogenesis
KW - Biomarker
KW - Lymphangiogenesis
KW - TMK-1
KW - Vascular endothelial growth factor receptor-3
KW - Vascular endothelial growth factor-C
KW - Vascular endothelial growth factor-D
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U2 - 10.3892/ol.2019.1000
DO - 10.3892/ol.2019.1000
M3 - Article
AN - SCOPUS:85062028578
SN - 1792-1074
VL - 17
SP - 3097
EP - 3102
JO - Oncology Letters
JF - Oncology Letters
IS - 3
ER -