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10.1245/s10434-007-9746-4
Annals of Surgical Oncology 15:1530-1537 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Clinical Significance of BMP7 in Human Colorectal Cancer

Kazuo Motoyama, MD1,2, Fumiaki Tanaka, MD, PhD1, Yoshimasa Kosaka, MD1, Koshi Mimori, MD, PhD1, Hiroyuki Uetake, MD, PhD2, Hiroshi Inoue, MD, PhD1, Kenichi Sugihara, MD, PhD2 and Masaki Mori, MD, PhD, FACS1

1 Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu, 874-0838, Japan
2 Department of Surgical Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

Correspondence: Address correspondence and reprint requests to: Masaki Mori, MD, PhD, FACS; E-mail: mmori{at}tsurumi.beppu.kyushu-u.ac.jp

Background: Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor (TGF)-β superfamily. Recent studies demonstrated that the expression patterns of BMPs are altered in several tumors. The purpose of the current study was to examine the expression of BMP7 in malignant and normal colorectal tissues, and to analyze whether BMP7 expression levels correlate with clinicopathological variables and prognosis in colorectal cancer.

Methods: Paired colorectal tissue samples from cancer and corresponding nonmalignant tissues were obtained from 65 patients who underwent surgical resection for colorectal cancer. The expression status of BMP7 mRNA was investigated by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and protein expression was analyzed by an immunohistochemical study.

Results: Quantitative real-time RT-PCR showed that BMP7 mRNA expression in cancerous tissue was significantly higher than that in normal tissue (p < 0.0001). An immunohistochemical study revealed that BMP7 was predominantly expressed in cancer cells. Elevated BMP7 expression was significantly correlated with depth of tumor invasion, liver metastasis, liver recurrence, advanced Dukes’ classification, and cancer-related death (p < 0.05, 0.001, 0.01, 0.05 and 0.01, respectively). Furthermore, patients with the highest levels of BMP7 expression showed the poorest prognosis (p < 0.01). A multivariate analysis showed that BMP7 expression status was an independent prognostic factor of overall survival (relative risk, 2.29; 95% confidence interval, 1.08–5.30; p < 0.05).

Conclusions: Expression of BMP7 in colorectal tumors correlates with parameters of pathological aggressiveness such as liver metastasis and poor prognosis. Thus, BMP7 could be a useful clinical marker for colorectal cancer patients.

Key Words: BMP7 • Colorectal cancer • Liver metastasis • Prognosis






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