Clinical significance of RCAS1 as a biomarker of ovarian cancer.

Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with advanced disease of various malignancies including ovarian cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its clinical significance and biologic function in ovarian cancer patients are unclear. Here, we evaluated serum RCAS1 concentrations to clarify its clinical significance and biologic activity in ovarian cancer. Via ELISA, we measured serum RCAS1 concentrations in samples from 75 healthy blood donors and 97 patients, 36 with ovarian benign tumor and 61 with ovarian cancer. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Ovarian cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors and ovarian tumor patients (P<0.05). RCAS1 level was significantly different according to histologic subtype for both ovarian tumor and cancer patients (P=0.0266 and 0.0074, respectively). RCAS1 values were also significantly associated with response to treatment (P<0.001). The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1 (P=0.0074). RCAS1 may be a biomarker of ovarian cancer by virtue of its ability to predict results of treatment and inhibit immune cell growth.

[1]  S. Miyamoto,et al.  Clinical significance of RCAS1 as a biomarker of uterine cancer. , 2006, Gynecologic oncology.

[2]  Gerard Tromp,et al.  Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. , 2006, Cancer research.

[3]  T. Kaku,et al.  Expression of RCAS1 in Female Genital Organs , 2005, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[4]  S. Miyamoto,et al.  Invasive potency related to RCAS1 expression in uterine cervical cancer. , 2005, Gynecologic oncology.

[5]  Masao Tanaka,et al.  Novel serum tumor marker, RCAS1, in pancreatic diseases. , 2005, World journal of gastroenterology.

[6]  K. Kotoh,et al.  Significance of RCAS1 antigen in hepatocellular, cholangiocellular and pancreatic carcinomas , 2005, Journal of gastroenterology and hepatology.

[7]  S. Miyamoto,et al.  Association between RCAS1 expression and microenvironmental immune cell death in uterine cervical cancer. , 2005, Gynecologic oncology.

[8]  E. Petricoin,et al.  Biomarkers of ovarian tumours. , 2004, European journal of cancer.

[9]  Chung-Liang Ho,et al.  Characterization of Active Mitogen-Activated Protein Kinase in Ovarian Serous Carcinomas , 2004, Clinical Cancer Research.

[10]  Rosemary Steinmetz,et al.  Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation. , 2004, Molecular endocrinology.

[11]  T Suzuki,et al.  Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer , 2004, British Journal of Cancer.

[12]  Usha Menon,et al.  Progress and Challenges in Screening for Early Detection of Ovarian Cancer* , 2004, Molecular & Cellular Proteomics.

[13]  S. Miyamoto,et al.  Association between RCAS1 expression and clinical outcome in uterine endometrial cancer , 2003, British Journal of Cancer.

[14]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[15]  H. Nawata,et al.  Expression and Diagnostic Evaluation of the Human Tumor–Associated Antigen RCAS1 in Pancreatic Cancer , 2003, Pancreas.

[16]  E. Dı́az-Rodrı́guez,et al.  Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases. , 2002, The Biochemical journal.

[17]  H. Nawata,et al.  Aberrant intracellular localization of RCAS1 is associated with tumor progression of gastric cancer. , 2001, International journal of oncology.

[18]  U. Rodeck,et al.  Production and pro-apoptotic activity of soluble CD95 ligand in pancreatic carcinoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  G. Rustin,et al.  Role of tumour markers in monitoring epithelial ovarian cancer , 2000, British Journal of Cancer.

[20]  M. Nakashima,et al.  Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1 , 1999, Nature Medicine.

[21]  I. Jacobs,et al.  Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation , 1999, British Journal of Cancer.

[22]  T. Kaku,et al.  The prognostic significance of tumor-associated antigen 22-1-1 expression in adenocarcinoma of the uterine cervix. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  K. Tham,et al.  A preliminary study of the immunohistochemical detection of a novel tumour marker, 22-1-1 antigen, in gynaecological cancer specimens. , 1999, Annals of the Academy of Medicine, Singapore.

[24]  E. Mekada,et al.  A metalloprotease–disintegrin, MDC9/meltrin‐γ/ADAM9 and PKCδ are involved in TPA‐induced ectodomain shedding of membrane‐anchored heparin‐binding EGF‐like growth factor , 1998, The EMBO journal.

[25]  T. Kaku,et al.  Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous neoplasias. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  T. Kaku,et al.  A novel tumor‐associated antigen expressed in human uterine and ovarian carcinomas , 1996, Cancer.

[27]  P. Schwartz,et al.  Is early detection of ovarian cancer possible? , 1995, Annals of medicine.

[28]  P. Heinrich,et al.  Soluble receptors for cytokines and growth factors: generation and biological function. , 1994, The Biochemical journal.

[29]  N. Natarajan,et al.  Comparison of CA 125 after three courses of chemotherapy and results of second-look surgery. , 2000, European journal of gynaecological oncology.

[30]  園田 顕三 A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas , 1996 .

[31]  J. Massagué,et al.  Membrane-anchored growth factors. , 1993, Annual review of biochemistry.

[32]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.