Prognostic significance of immunohistochemical staining for myoferlin in clear cell renal cell carcinoma and its association with epidermal growth factor receptor expression.

OBJECTIVES:To reveal the prognostic significance of myoferlin expression in clear cell renal cell carcinoma (ccRCC) and its association with epidermal growth factor receptor (EGFR) expression and cytoplasmic features based on lipogenic metabolism. MATERIALS AND METHODS:Immunohistochemical (IHC) staining for myoferlin and EGFR was conducted on 450 resected ccRCC specimens using tissue microarray, which was measured semiquantitatively. MYOF and EGFR mRNA data were acquired from the TCGA database. The cytoplasmic characteristics of ccRCC based on lipogenic metabolism were retrieved from previous study. Survival analyses were carried out for progression-free, overall, and cancer-specific survival using Kaplan-Meier with the log-rank tests and Cox regression models. Discrimination of prognostic prediction was analyzed by Harrell's C-index. In addition, cross-correlation analyses of myoferlin expression with clinicopathological characteristics and EGFR expression were performed using Pearson's χ², Mann-Whitney U, and Pearson's r tests. RESULTS:High expression of myoferlin, which was related to high WHO grade (P< 0.001) and high TNM stage (P= 0.074), was significantly associated with short progression-free (P< 0.001), overall (P< 0.001), and cancer-specific survival (P< 0.001) of ccRCC patients. In multivariate analysis, IHC staining for myoferlin was independently associated with progression-free (hazard ratio [HR] = 1.734, P= 0.021), overall (HR = 1.750, P= 0.004), and cancer-specific (HR = 1.723, P= 0.044) survival when adjusted for TNM stage and WHO grade, with significantly improved C-indices. Furthermore, the expression of myoferlin and EGFR showed positive relationship at the protein (P< 0.001) and at the mRNA levels (r = 0.478, P< 0.001). In addition, clear to light-granular cytoplasm, representative of low-risk lipogenic metabolism, was predominantly observed in myoferlin-low ccRCC (P= 0.004). CONCLUSIONS:IHC staining for myoferlin was a useful prognostic biomarker of ccRCC. We hypothesize that EGFR overexpression and lipogenic metabolism alteration underlie the protumorous functions of myoferlin on ccRCC.

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