Clinical Significance of BMP7 in Human Colorectal Cancer
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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.
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.
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).
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.
KeywordsBMP7 Colorectal cancer Liver metastasis Prognosis
Presented in part at The Society of Surgical Oncology 60th Annual Cancer Symposium, March 15–18, 2007, Washington, DC. This work was supported in part by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (grant numbers 17109013, 18390367, 18590333, 18659384, 18890133, 18015039, 19390336, and 19591509). We thank T. Shimooka, K. Ogata, M. Oda, M. Kasagi, and Y. Nakagawa for excellent technical assistance.
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