Expression of bone morphogenetic protein-2 and its receptors in epithelial ovarian cancer and their influence on the prognosis of ovarian cancer patients
Journal of Experimental & Clinical Cancer Research
REexseparcrhession of bone morphogenetic protein-2 and its receptors in epithelial ovarian cancer and their influence on the prognosis of ovarian cancer patients
Ying Ma 0
Lin Ma 0
Quan Guo 0
Shulan Zhang 0
0 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University , Shenyang 110004 , China
Background: To determine the expression of bone morphogenetic protein-2 (BMP-2) and its receptors BMPRIA, BMPRIB, and BMPRII in epithelial ovarian cancer (EOC) and to analyze their influence on the prognosis of ovarian cancer patients. Methods: Semi-quantitative RT-PCR and western blot were applied to detect the expression of BMP-2 and its receptors BMPRIA, BMPRIB, and BMPRII in EOC, benign ovarian tumors, and normal ovarian tissue at the mRNA and protein levels. Immunohistochemistry was used to determine the expression of BMP-2 and its receptors in 100 patients with EOC to analyze their influence on the five-year survival rate and survival time of ovarian cancer patients. Results: (1) The mRNA and protein expression levels of BMP-2, BMPRIB, and BMPRII in ovarian cancer tissue were remarkably lower than those in benign ovarian tumors and normal ovarian tissue, while no significant differences in BMPRIA expression level was found among the three kinds of tissues. (2) The five-year survival rate and the average survival time after surgery of EOC patients with positive expression of BMP-2, BMPRIB, and BMPRII were remarkably higher than those of patients with negative expression of BMP-2, BMPRIB, and BMPRII. BMPRIA expression was not associated with the five-year survival rate or with the average survival time of ovarian cancer patients. Conclusions: BMP-2, BMPRIB, and BMPRII exhibited low expression in EOC tissue, and variation or loss of expression may indicate poor prognosis for ovarian cancer patients.
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Background
Ovarian cancer is the most lethal type of malignant
tumors of the female reproductive system, and despite
recent developments in diagnosis and treatment
techniques, the five-year survival rate for ovarian cancer
patients is only 20-40%[1]. The low survival rate is likely
due to the lack of early symptoms for this cancer; most
patients are diagnosed at an advanced stage and exhibit
widespread metastasis. At present, the pathological
causes of ovarian cancer are unclear. Thus, it is urgent to
investigate and search for novel treatment regimens.
The development of tumors is believed to be a complex
process involving several genes and several factors, and
more and more influencing factors are emerging. In
recent years, researchers have focused on the correlation
between bone morphogenetic proteins (BMPs) and the
presence of tumors. BMP is a member of the
transforming growth factor- superfamily. Initially, it was thought
to induce bone formation and chondrogenesis in vivo,
and current evidence suggests that it also participates in
various biological processes of cells, such as proliferation,
differentiation, and apoptosis[2]. BMP signaling is
mediated by transmembrane serine/threonine kinases,
namely, BMPRI (BMPRIA, BMPRIB) and BMPRII
receptors[3]. There are 16 kinds of BMPs, and the majority of
studies have focused on BMP-2, which has been shown to
play a crucial role in the occurrence and development of
breast cancer[4-6], lung cancer[7-11], prostatic
carcinoma[12-14], and colon cancer[15,16]. However, the
correlation between BMP-2 and ovarian cancer remains
unclear. This study was designed to determine the
expression of BMP-2 and its receptors in epithelial
ovarian cancer, benign ovarian tumors, and normal ovarian
tissue and to analyze their influence on the five-year
survival rate and average survival time of ovarian cancer
patients.
RT-PCR samples: A total of 29 EOC patients, 32 benign
ovarian tumor patients, and 10 patients with normal
ovarian tissue were recruited from Shengjing Hospital,
which is affiliated with China Medical University,
between August 2005 and August 2007.
Western blot samples: A total of 15 EOC patients, 15
benign ovarian tumor patients, and 10 patients with
normal ovarian tissue were recruited from Shengjing
Hospital, which is affiliated with China Medical University,
between August 2005 and August 2007.
Immunohistochemistry samples: One hundred
paraffin-embedded specimens of EOC preserved at the
Department of Pathology of Shengjing Hospital between
January 1997 and August 2001 were included in this
study. Specimens were examined for histological grade
based on World Health Organization criteria. All EOC
patients were grade II and grade III. The tumor stages
were determined according to the International
Federation of Gynecology and Obstetrics (FIGO) with surgically
and cytologically stage performed, all EOC patients had
stage III and stage IV. All specimens were fixed with
paraformaldehyde, embedded in paraffin, and prepared as
serial slices of 4 m in thickness.
All experiment subjects had complete (...truncated)