Abstract
BackgroundColorectal cancer (CRC) is caused by genetic aberrations. MACROD2 is commonly involved in somatic focal DNA copy number losses, in more than one-third of CRCs. In this study, we aimed to investigate the association of MACROD2 protein expression with clinical outcome in stage II and stage III colon cancer.MethodsTissue microarrays (TMA) containing formalin-fixed paraffin-embedded tissue cores from 386 clinically well-annotated primary stage II and III colon cancers were stained by immunohistochemistry and evaluated for MACROD2 protein expression. Disease-free survival (DFS) analysis was performed to estimate association with clinical outcome.ResultsLoss of nuclear MACROD2 protein expression in epithelial neoplastic cells of stage III microsatellite stable (MSS) colon cancers was associated with poor DFS within the subgroup of 59 patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (p=0.005; HR=3.8, 95% CI 1.4-10.0).ConclusionThese data indicate that low nuclear expression of MACROD2 is associated with poor prognosis of patients with stage III MSS primary colon cancer who were treated with 5-FU-based adjuvant chemotherapy.
Highlights
Colorectal cancer (CRC) has a worldwide incidence of over 1.3 million and is one of the leading causes of cancer-related deaths [1]
Loss of nuclear MACROD2 protein expression in epithelial neoplastic cells of stage III microsatellite stable (MSS) colon cancers was associated with poor Disease-free survival (DFS) within the subgroup of 59 patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (p=0.005; Hazard Ratios (HR)=3.8, 95% CI 1.4-10.0)
These data indicate that low nuclear expression of MACROD2 is associated with poor prognosis of patients with stage III MSS primary colon cancer who were treated with 5-FU-based adjuvant chemotherapy
Summary
Colorectal cancer (CRC) has a worldwide incidence of over 1.3 million and is one of the leading causes of cancer-related deaths [1]. To estimate the prognosis of CRC patients, tumors are currently classified into stage I to IV according to the tumor-node-metastasis (TNM) staging, which is primarily based upon histopathological features of the tumor. Because somatic DNA alterations enable tumors to progress, characterization of genomic inter-tumor heterogeneity may reveal promising candidate biomarkers that could improve patient stratification for prognosis and therapy prediction. Colorectal cancer (CRC) is caused by genetic aberrations. MACROD2 is commonly involved in somatic focal DNA copy number losses, in more than onethird of CRCs. In this study, we aimed to investigate the association of MACROD2 protein expression with clinical outcome in stage II and stage III colon cancer
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