Elevated serum levels of human relaxin-2 in patients with esophageal squamous cell carcinoma

AIM: To assess the prognostic value of serum human relaxin 2 (H2 RLN) level in patients with esophageal squamous cell carcinoma (ESCC). METHODS: From October 1998 to September 2009, 146 patients with histopathologically confirmed ESCC were enrolled in this study. One hundred patients underwent en bloc esophagectomy, and 46 patients with unresectable tumors underwent palliative surgery. Five of the 146 patients died of surgical complications. Serum levels of H2 RLN were measured by enzyme linked immunosorbent assay. The relationship between serum H2 RLN level and each of the clinicopathological parameters was analyzed using the χ² test. Patients were classified into two groups according to their H2 RLN level (< 0.462 ng/mL vs≥ 0.462 ng/mL). When any analysis cell had fewer than five cases, the Fisher’s exact test was used. The statistical difference between groups A and B in each clinicopathological category was determined by the Student’s t test (two-tailed) or analysis of variance. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: ESCC patients tended to have significantly higher serum H2 RLN concentrations (0.48 ± 0.17 ng/mL, n = 141) compared with the healthy control group (0.342 ± 0.12 ng/mL, n = 112). There was a significant difference between patients with lymph node involvement (0.74 ± 0.15 ng/mL, n = 90), distant metastasis (0.90 ± 0.19 ng/mL, n = 32) and those without lymph node involvement (0.45 ± 0.12 ng/mL, n = 51), and distant metastasis (0.43 ± 0.14 ng/mL, n = 109), respectively (P < 0.01). Patients with high H2 RLN levels (≥ 0.462 ng/mL) had a poorer prognosis than patients with low serum H2 RLN levels (< 0.462 ng/mL; P = 0.0056). The H2 RLN level was also correlated with survival and tumor-node-metastasis staging, but not with age, tumor size, gender, lymphovascular invasion or the histological grade of tumors. Cox regression analysis showed that H2 RLN was an independent variable. CONCLUSION: Serum concentrations of H2 RLN are frequently elevated in ESCC patients and are correlated with disease metastasis and survival. Serum concentrations of H2 RLN may be an important prognostic marker in ESCC patients.