Objectives: Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with prognosis of various malignancies including uterine cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its biologic function in cancer patients is unclear. Here, we evaluated serum RCAS1 concentrations to clarify its biologic activity in uterine cancer.
Methods: Via ELISA, we measured serum RCAS1 concentrations in samples from 54 healthy blood donors and 113 patients-63 with cervical cancer and 50 with endometrial cancer. We also counted the peripheral lymphocyte number. 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.
Results: Uterine cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors (P<0.05). Patients with adenocarcinoma had significantly higher RCAS1 concentrations than did those with squamous cell carcinoma (P=0.0340). RCAS1 values were also significantly associated with response to treatment (P<0.001). FasL and TNF-alpha serum concentrations were not significantly different for the different groups, however. The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1. Peripheral lymphocyte number and serum RCAS1 concentration were inversely related (P=0.0310).
Conclusion: RCAS1 may be a biomarker of uterine cancer because of its potential to predict results of uterine cancer treatment and inhibit growth of immune cells.