Clinical significance of BMP7 in human colorectal cancer.
BACKGROUND
Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor (TGF)-beta 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.
Motoyama
Kazuo
K
Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu, 874-0838, Japan.
Tanaka
Fumiaki
F
Kosaka
Yoshimasa
Y
Mimori
Koshi
K
Uetake
Hiroyuki
H
Inoue
Hiroshi
H
Sugihara
Kenichi
K
Mori
Masaki
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
C525819:BMP7 protein, human; D014408:Biomarkers, Tumor; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta