cMET and phospho-cMET protein levels in breast cancers and survival outcomes

Kanwal P. Raghav, Wenting Wang, Shuying Liu, Mariana Chavez-MacGregor, Xiaolong Meng, Gabriel N. Hortobagyi, Gordon B. Mills, Funda Meric-Bernstam, George R. Blumenschein, Ana M. Gonzalez-Angulo

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    Abstract

    Purpose: To evaluate cMET (mesenchymal-epithelial transition factor gene) and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes. Experimental Design: We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan-Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics. Results: Median age was 51 years. There were 140 (54.5%) hormone receptor (HR) positive, 53 (20.6%) HER2 positive, and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P < 0.128) and p-cMET (P < 0.088) by breast cancer subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor for RFS [HR: 2.44, 95% confidence interval (CI): 1.34-4.44, P = 0.003 and HR: 1.64, 95% CI: 1.04-2.60, P = 0.033] and OS (HR: 3.18, 95% CI: 1.43-7.11, P = 0.003 and HR: 1.92, 95% CI: 1.08-3.44, P = 0.025). Within breast cancer subtypes, high cMET levels were associated with worse RFS (P = 0.014) and OS (P = 0.006) in HR-positive tumors, and high p-cMET levels were associated with worse RFS (P = 0.019) and OS (P = 0.014) in HER2-positive breast cancers. In multivariable analysis, patients with high cMET had a significantly higher risk of recurrence (HR: 2.06, 95% CI: 1.08-3.94, P = 0.028) and death (HR: 2.81, 95% CI: 1.19-6.64, P = 0.019). High p-cMET level was associated with higher risk of recurrence (HR: 1.79, 95% CI: 1.08-2.95.77, P = 0.020). Conclusions: High levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis.

    Original languageEnglish (US)
    Pages (from-to)2269-2277
    Number of pages9
    JournalClinical Cancer Research
    Volume18
    Issue number8
    DOIs
    StatePublished - Apr 15 2012

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Raghav, K. P., Wang, W., Liu, S., Chavez-MacGregor, M., Meng, X., Hortobagyi, G. N., Mills, G. B., Meric-Bernstam, F., Blumenschein, G. R., & Gonzalez-Angulo, A. M. (2012). cMET and phospho-cMET protein levels in breast cancers and survival outcomes. Clinical Cancer Research, 18(8), 2269-2277. https://doi.org/10.1158/1078-0432.CCR-11-2830