Figure 1.

RAB5A predicts poor clinical outcome in breast cancer patients and its expression is elevated in breast cancer lymph node metastases. (A–D) Kaplan–Meier plots for breast cancer patients stratified by RAB5A expression for the following groups of patients: (A) all 980 patients; (B) 695 patients with lymph node negative (N0) breast tumors; (C) 528 patients with lymph node–negative and ER-positive (N0 ER+) breast tumors; (D) 166 patients with lymph node–negative, ER-positive, and Grade 2 (N0 ER+ G2) breast tumors. High RAB5A, >75th percentile; low RAB5A, ≤75th percentile. Y axes = the probability of local and distant relapse free survival (DFS). X axes = years of follow up. P-values are from a log-rank test. (E) RAB5A prognostic significance is independent from Ki67, and its expression is not associated with a proliferation signature. (E, left) Multivariate analysis with a Cox proportional hazard model on prognosis of patients with breast cancer. The RAB5A and Ki67 genes were used as covariates. High RAB5A or Ki67 expression levels, >75th percentile of the normalize expression distribution. Low RAB5A or Ki67 expression levels, ≤75th percentile. HR, hazard ratio by Cox model. 95% CI, 95% confidence intervals of HR. P-value, likelihood ratio χ2 test on the null hypothesis that the parameter estimate for the RAB5A high/low, or Ki67 high/low, covariate is zero. (E, right) Gene set enrichment analysis (GSEA) analysis of a known proliferation signature (Ben-Porath et al., 2008) among genes ranked by signal-to-noise metric based on their correlation with Ki67 high/low or RAB5A high/low. FDR, false discovery rate based on 1,000 random permutations of class labels. (F) IHC staining of RAB5 on FFPE samples of a human primary infiltrating breast tumor (PT) and matched nodal metastasis (NM). N, normal duct; L, normal negative lymphocytes. Boxed regions are enlarged below. Bar, 500 µm. (G) Percentage of low and high RAB5A-expressing primary tumors and metastases. Normal breast tissue scores always range between 0 and 1. **, P < 0.000271 (χ2 test).

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