Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

Takahashi,Yusuke; Sawada,Genta; Sato,Tetsuya; Kurashige,Junji; Mima,Kosuke; Matsumura,Tae; Uchi,Ryutaro; Ueo,Hiroki; Ishibashi,Masahisa; Takano,Yuki; Akiyoshi,Sayuri; Eguchi,Hidetoshi; Sudo,Tomoya; Sugimachi,Keishi; Tanaka,Jun‑Ichi; Kudo,Shin-Ei; Doki,Yuichiro; Mori,Masaki; Mimori,Koshi

doi:10.3892/or.2013.2602

Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

Authors:
- Yusuke Takahashi
- Genta Sawada
- Tetsuya Sato
- Junji Kurashige
- Kosuke Mima
- Tae Matsumura
- Ryutaro Uchi
- Hiroki Ueo
- Masahisa Ishibashi
- Yuki Takano
- Sayuri Akiyoshi
- Hidetoshi Eguchi
- Tomoya Sudo
- Keishi Sugimachi
- Jun‑Ichi Tanaka
- Shin-Ei Kudo
- Yuichiro Doki
- Masaki Mori
- Koshi Mimori
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Affiliations: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan, Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan, Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan, Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, Suita, Japan
Published online on: July 8, 2013 https://doi.org/10.3892/or.2013.2602
Pages: 1488-1496

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Abstract

Tumor size indicates the extent of cell proliferation in most cases of colorectal cancer (CRC), although there are some advanced small tumors with metastases. Lymph node metastasis is a significant factor that greatly impacts disease prognosis in CRC cases. The underlying factors that cause lymph node metastasis in CRC cells are not fully understood. We investigated the mechanism that might induce CRC metastasis by focusing on smaller sized (<2 cm) invasive tumors. We carried out gene expression array analysis for CRC cases; group 1 consisted of 6 cases with tumors <2 cm with metastases, and group 2 consisted of 65 cases with tumors >2 cm without metastases. Results were validated using gene expression array data from an additional 77 cases and another bulk case set of 172 cases. Gene ontology and pathway analysis using microarray data revealed that anti-apoptotic activity had a crucial role in CRC metastasis. High mobility group A1 (HMGA1) was identified as a biomarker for poor prognosis and metastasis formation. HMGA1 expression levels were higher in lymph node-positive cases than in lymph node-negative cases, even in subgroup analysis of submucosal invasive cases. The present study strongly supports the clinical significance of HMGA1 expression as a predictive indicator of lymph node metastasis in CRC cases, even in submucosal invasive cases which could be cured by local resection.

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