American Association for Cancer Research
10780432ccr170996-sup-181256_3_supp_4351992_rydzck.pptx (77.06 kB)

Figure S1 from Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis

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posted on 2023-03-31, 19:45 authored by Vasily N. Aushev, Eunjee Lee, Jun Zhu, Kalpana Gopalakrishnan, Qian Li, Susan L. Teitelbaum, James Wetmur, Davide Degli Esposti, Hector Hernandez-Vargas, Zdenko Herceg, Humberto Parada, Regina M. Santella, Marilie D. Gammon, Jia Chen

Fig. S1. Correlation between IHC-defined status and gene expression levels for estrogen receptor (ER, left panel) and progesterone receptor (PR, right panel). Each panel shows, left to right, distribution of gene expression values (vertical axis) for IHC-negative, IHC-positive and IHC-unknown groups. Red lines indicate the cut-off chosen (see below).





Purpose: Breast cancer is among the leading causes of cancer-related death; discovery of novel prognostic markers is needed to improve outcomes. Combining systems biology and epidemiology, we investigated miRNA-associated genes and breast cancer survival in a well-characterized population-based study.Experimental Design: A recently developed algorithm, ActMiR, was used to identify key miRNA “activities” corresponding to target gene degradation, which were predictive of breast cancer mortality in published databases. We profiled miRNA-associated genes in tumors from our well-characterized population-based cohort of 606 women with first primary breast cancer. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI), after 15+ years of follow-up with 119 breast cancer–specific deaths.Results: miR-500a activity was identified as a key miRNA for estrogen receptor–positive breast cancer mortality using public databases. From a panel of 161 miR-500a–associated genes profiled, 73 were significantly associated with breast cancer–specific mortality (FDR < 0.05) in our population, among which two clusters were observed to have opposing directions of association. For example, high level of SUSD3 was associated with reduced breast cancer–specific mortality (HR = 0.3; 95% CI, 0.2–0.4), whereas the opposite was observed for TPX2 (HR = 2.7; 95% CI, 1.8–3.9). Most importantly, we identified set of genes for which associations with breast cancer–specific mortality were independent of known prognostic factors, including hormone receptor status and PAM50–derived risk-of-recurrence scores. These results are validated in independent datasets.Conclusions: We identified novel markers that may improve prognostic efficiency while shedding light on molecular mechanisms of breast cancer progression. Clin Cancer Res; 24(3); 581–91. ©2017 AACR.

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