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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2019

01-05-2019 | Metastasis | Translational Research and Biomarkers

Homeobox C10 Influences on the Malignant Phenotype of Gastric Cancer Cell Lines and its Elevated Expression Positively Correlates with Recurrence and Poor Survival

Authors: Takashi Miwa, MD, Mitsuro Kanda, MD, PhD, FACS, Shinichi Umeda, MD, Haruyoshi Tanaka, MD, PhD, Chie Tanaka, MD, PhD, Daisuke Kobayashi, MD, PhD, Masaya Suenaga, MD, PhD, Masamichi Hayashi, MD, PhD, Suguru Yamada, MD, PhD, FACS, Goro Nakayama, MD, PhD, Masahiko Koike, MD, PhD, Yasuhiro Kodera, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 5/2019

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Abstract

Background

The detection of molecules and mechanisms affecting the malignant phenotype of gastric cancer cells may contribute to the identification of biomarkers for metastasis and recurrence, and such molecules may serve as targets of therapy. For this purpose, in this study transcriptome analysis was performed using surgically resected specimens from patients with gastric cancer with synchronous metastasis. We identified homeobox C10 (HOXC10) as the most highly expressed gene in gastric cancer tissues compared with the adjacent noncancerous gastric mucosa.

Methods

Polymerase chain reaction (PCR) array analysis was performed to identify genes coordinately expressed with HOXC10. The effects of inhibiting HOXC10 on malignant phenotype was evaluated using HOXC10 knockout gastric cancer cell lines, and antibody array analysis was performed to assess the effect of HOXC10 knockout on intracellular signaling. We used a mouse subcutaneous xenograft model to evaluate the tumorigenicity. HOXC10 expression was determined in gastric cancer tissues acquired from 300 patients with gastric cancer.

Results

PCR array analysis revealed that the levels of HOXC10 messenger RNA positively correlated with those of FGFBP1 and SOX10. The phosphorylation of ERK1/2 was decreased in HOXC10 knockout cells. HOXC10 knockout significantly suppressed proliferation by increasing apoptosis and reducing the migration and invasiveness of gastric cancer cells. Mouse xenograft models revealed that the tumorigenicity of HOXC10 knockout cells was attenuated compared with the parental cells. The relatively high expression levels of HOXC10 in gastric cancer tissues were significantly associated with hepatic and peritoneal recurrence, as well as worse prognosis.

Conclusions

Our results indicated that HOXC10 enhances the malignant phenotype of gastric cancer cells. The expression levels of HOXC10 may therefore serve as a prognostic biomarker and the products of HOXC10 may provide targets of therapy.
Appendix
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Metadata
Title
Homeobox C10 Influences on the Malignant Phenotype of Gastric Cancer Cell Lines and its Elevated Expression Positively Correlates with Recurrence and Poor Survival
Authors
Takashi Miwa, MD
Mitsuro Kanda, MD, PhD, FACS
Shinichi Umeda, MD
Haruyoshi Tanaka, MD, PhD
Chie Tanaka, MD, PhD
Daisuke Kobayashi, MD, PhD
Masaya Suenaga, MD, PhD
Masamichi Hayashi, MD, PhD
Suguru Yamada, MD, PhD, FACS
Goro Nakayama, MD, PhD
Masahiko Koike, MD, PhD
Yasuhiro Kodera, MD, PhD, FACS
Publication date
01-05-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07166-5

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