Abstract
BackgroundThe purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and β-catenin overexpression in colorectal cancer (CRC) patients.MethodsUsing immunohistochemistry (IHC), we measured the c-MYC and β-catenin expression in 367 consecutive CRC patients retrospectively (cohort 1). Also, c-MYC expression was measured by mRNA in situ hybridization. Moreover, to analyze regional heterogeneity, three sites of CRC including the primary, distant and lymph node metastasis were evaluated in 176 advanced CRC patients (cohort 2).ResultsIn cohort 1, c-MYC protein and mRNA overexpression and ß-catenin nuclear expression were found in 201 (54.8 %), 241 (65.7 %) and 221 (60.2 %) of 367 patients, respectively, each of which was associated with improved prognosis (P = 0.011, P = 0.012 and P = 0.033, respectively). Moreover, co-expression of c-MYC and ß-catenin was significantly correlated with longer survival by univariate (P = 0.012) and multivariate (P = 0.048) studies. Overexpression of c-MYC protein was associated with mRNA overexpression (ρ, 0.479; P < 0.001) and nuclear ß-catenin expression (ρ, 0.282; P < 0.001). Expression of c-MYC and ß-catenin was heterogeneous depending on location in advanced CRC patients (cohort 2). Nevertheless, both c-MYC and ß-catenin expression in primary cancer were significantly correlated with improved survival in univariate (P = 0.001) and multivariate (P = 0.002) analyses. c-MYC and ß-catenin expression of lymph node or distant metastatic tumor was not significantly correlated with patients’ prognosis (P > 0.05).ConclusionsCo-expression of c-MYC and ß-catenin was independently correlated with favorable prognosis in CRC patient. We concluded that the expression of c-MYC and ß-catenin might be useful predicting indicator of CRC patient’s prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2770-7) contains supplementary material, which is available to authorized users.
Highlights
The purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and β-catenin overexpression in colorectal cancer (CRC) patients
Increased levels of the c-MYC mRNA transcript were associated with microsatellite stable CRC (P = 0.019), located in the sigmoid colon and rectum, and with less aggressive features, to c-MYC protein overexpression
SScatenin nuclear expression was frequently detected in tumors of the recto-sigmoid colon, of low-grade differentiation (P = 0.006), of small size (P = 0.007) and microsatellite stable CRC (P < 0.001)
Summary
The purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and β-catenin overexpression in colorectal cancer (CRC) patients. It is well established that APC gene mutation, a key driver of adenoma-carcinoma transition, often leads to altered ß-catenin regulation via the wellstudied Wnt signaling pathway [12,13,14]. Recent studies reported CRCs with marked WNT and c-MYC signaling activation as a distinct molecular subtype by gene expressionbased CRC classifications, which was associated with relatively better prognosis [17, 18]. It suggests that CRCs with activated c-MYC via Wnt signaling pathway have distinct clinicopathologic characteristics, but it has not been confirmed
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