Decreased expression of mucin 18 is associated with unfavorable postoperative prognosis in patients with clear cell renal cell carcinoma

Abstract

Background: MUC18 is correlated with tumor progression and metastasis in types of malignancy. But the role of MUC18 in clear cell renal cell carcinoma remains unclear. In this study, we aimed to investigate the expression of MUC18 and its correlation with clinical outcomes in clear cell renal cell carcinoma.

Patients and methods: Immunohistochemical staining was performed in samples from 288 patients with clear cell renal cell carcinoma. We used Kaplan-Meier method and Cox proportional hazard models to value the association between MUC18 expression and clinical outcome. Nomogram was constructed to predict overall survival at 5 and 8 years after nephrectomy.

Results: MUC18 expression was significantly decreased in tumor compared to non-tumor tissue (P<0.001). Lower MUC18 expression in tumor predicted a shorter survival time (P=0.007). By multivariate cox analysis, MUC18 was defined as an independent prognostic factor (P=0.006). The nomogram performed better in predicting 5- and 8-year overall survival than the TNM stage alone in clear cell renal cell carcinoma.

Conclusion: MUC18 is an independent prognostic factor for clear cell renal cell carcinoma and could be incorporated with the other parameters to predict 5- and 8-year overall survival for clear cell renal cell carcinoma patients.

Keywords: Clear cell renal cell carcinoma; disease free survival; mucin 18; nomogram; overall survival.

Figure 1

Immunohistochemical analysis of MUC18 expression in ccRCC. A: High MUC18 expression in non-tumor tissue; B: Low MUC18 expression in non-tumor tissue; C: High MUC18 expression in tumor tissue; D: Low MUC18 expression in tumor tissue; E: IOD score of MUC18 expression in tumor and non-tumor tissue. P value, was calculated by paired t-test, <0.05 was regarded as statistically significant. Magnification 200×.

Figure 2

Kaplan-Meier analysis for overall survival and disease free survival of patients with ccRCC according to MUC18 expression. Overall survival according to tumor MUC18 expression in all (A), TNM I+II (C) and TNM III+IV (E) patients; Disease free survival according to tumor MUC18 expression in all (B), TNM I+II (D) and TNM III+IV (F) patients. P value, calculated by Log rank test, <0.05 was regarded as statistically significant.

Figure 3

Nomogram for predicting 5- and 8-year overall survival in patients with ccRCC. A: Nomogram for predicting clinical outcomes integrated with T stage (1/2/3/4), N stage (0/1), M stage (0/1), ECOS PS (1/2/3), and MUC18 expression level (Low/High); B: Calibration plot for nomogram predicted and observed 5-year survival rate; C: Calibration plot for nomogram predicted and observed 8-year survival rate. Line of dashes: ideal model; vertical bars, 95% confident interval. A higher total point indicated a more adverse outcome probability.