Abstract
BackgroundPrognostic assessment is crucial for optimal treatment. The aim of our study was to investigate the potential impact of estrogen receptor-α (ER-α) and progesterone receptor (PR) on the prognosis of colorectal cancer (CRC) patients who received curative resection.MethodsRetrospective evaluation of two independent cohorts of CRC patients maintained prospectively in 2009–2010 (training set) (n = 148) and 2007–2009 (internal validation set) (n = 485). Furthermore, we used an external independent CRC cohort from The Cancer Genome Atlas (TCGA) (n = 511) for further validation. ER-α and PR expression as well as other potential prognostic factors were retrospectively evaluated in training set with respect to overall survival (OS), local relapse free survival (LRFS) and distant metastasis free survival (DMFS). The prognostic factors found in training set will be validated in two validation cohorts.ResultsOn univariate analysis for the training set, OS, LRFS and DMFS were not associated with PR expression. While patients with ER-αexpression were found to have poor prognosis. In addition, multivariate analysis showed that ER-αexpression maintained significance with respect to OS (HR, 5.06; p = 0.002), LRFS (HR, 8.81; p = 0.002) and DMFS (HR, 8.07; p = 0.004). Similarly, ER-α expression showed prognostic significance with respect to OS with hazard ratios (HRs) of 1.572 (95% CI: 1.001–2.467, p = 0.049) and 1.624 (95% CI: 1.047–2.520, p = 0.031) for the internal and external validation cohort, respectively.ConclusionER-α expression was a biomarker of poor prognosis and it might inform treatment decision for high risk CRC patients. However, PR expression was not associated with survival outcomes.
Highlights
Prognostic assessment is crucial for optimal treatment
Impact of tumor expression of estrogen receptor-α (ER-α) and progesterone receptor (PR) on survival outcomes in training cohort To investigate the effect of tumor expression of ER-α, PR on the outcomes of patients with colorectal cancer (CRC), the 5-year actuarial overall survival (OS), distant metastasis free survival (DMFS) and local relapse free survival (LRFS) rates in training cohort were analyzed
Low and high ER-α expression demonstrated significant differences in the 5-year OS (89% vs. 47%, p < 0.001), LRFS (95% vs. 71%, p < 0.001) and DMFS (95% vs. 70%, p < 0.001) (Fig. 1, Tables 2 and 3) rates of CRC patients, while PR were not found to be significantly associated with improved 5-year OS, LRFS and DMFS rates (Additional file 1: Table S1)
Summary
The aim of our study was to investigate the potential impact of estrogen receptor-α (ER-α) and progesterone receptor (PR) on the prognosis of colorectal cancer (CRC) patients who received curative resection. Tumor markers are potentially useful in Recent investigations have suggested that the tumor cell expression of hormone receptors may have an impact on the prognosis of patients with CRC [4]. ER-α was reported to be implicated in the development and progression of colorectal cancers according to Caiazza et al [6] and Nussler et al [7], the prognostic value of ER-α in CRC needs to be investigated. A study from the United States suggested that the expression of PR by the tumor cells may be associated with a shorter patient survival [8]
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