Dysregulated expression of rab31, a member of the large Rab protein family of the Ras superfamily of small GTPases, has been observed in several types of cancer, including breast cancer. Rab31, depending on its expression level, may regulate the switch between an invasive versus proliferative phenotype of breast cancer cells in vitro. Moreover, gene expression of rab31 is induced by the C-terminal subunit of mucin-1 (MUC1-C) and estrogen receptors (ER). To gain further insights into the clinical relevance of rab31 and mucin-1 expression in breast cancer, we analyzed the relation between rab31 and mucin-1 (CA15-3) antigen levels in detergent tissue extracts of ER-positive (ER+) tumors and clinicopathological parameters as well as patients' prognosis. No significant correlation was observed between rab31 and CA15-3 antigen levels. Elevated rab31 antigen levels in tumor tissue extracts were significantly associated with higher tumor grade (P = 0.021). Strikingly, an inverse significant association was observed for CA15-3 with tumor grade (P = 0.032). Furthermore, high rab31 antigen levels were significantly associated with a high S-phase fraction (SPF, P = 0.047), whereas a trend for lower CA15-3 antigen levels in tumor tissue displaying higher SPF was observed. High rab31 antigen levels were significantly associated with poor 5-year disease-free survival (DFS) of ER+ breast cancer patients in univariate Cox regression analysis (HR = 1.91, 95% CI = 1.14-3.17, P = 0.013). In contrast, high levels of CA15-3 antigen levels were associated with better patients' prognosis (HR = 0.56, 95% CI = 0.33-0.95, P = 0.031). In multivariable analysis, rab31 antigen levels contributed independent prognostic information for DFS when adjusted for prognostically relevant clinicopathological parameters with a HR for high versus low values of 1.97 (95% CI = 1.09-3.54, P = 0.024), whereas CA15-3 antigen levels were not significant. Our results strongly suggest that rab31 antigen levels in tumor tissue are associated with the proliferative status, and rab31 represents an independent biomarker for prognosis in ER+ breast cancer patients. Total mucin-1 (CA 15-3) levels are rather inversely associated with tumor grade and SPF, and elevated levels even indicate prolonged DFS in ER+ breast cancer patients.

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