Expression Profiles in Stage II Colon Cancer According to APC Gene Status

Abstract

Colorectal cancer is one of the most common cancers in the world. Histoclinical staging is efficient, but combination with molecular markers may improve the classification of stage II cancers. Several tumor-suppressor genes have been associated with colorectal cancer, and the most frequent allelic losses have been extensively studied for their prognosis effect, but the results remain controversial. In a previous study, we found a possible influence of the chromosome 5 status in the development of liver metastases in stage II colon cancers. We have here investigated the role of the APC gene, located in chromosome arm 5q, in a series of 183 colon adenocarcinomas through a combined analysis of gene expression, mutation, allelic loss and promoter methylation, and metastasis occurrence. Point mutations were found in 73% of cases and allelic losses were found in 39%; 59% of tumors presented with a biallelic inactivation, with a very strong interdependence of the two APC hits (P = 2.1 x 10(-9)). No association was found between expression, number and type of APC alterations, and metastatic evolution. Our results show that the determination of APC status cannot help in the prediction of metastasis and cannot be used to subclassify stage II colon cancers.

Genomic Profiling of Stage II Colorectal Cancer Identifies Candidate Genes Associated with Recurrence-Free Survival, Tumor Location, and Differentiation Grade

“…As has been reported by others in CRC stage II [36,42], BRAF mutation here was not associated with RFS or with cancer-specific survival. However, BRAF is generally considered an independent predictor of a poor prognosis, and growing evidence suggests that this is particularly true for MSI stable tumors [12,14,35,36,39,41].…”

“…Central gene mutations (KRAS, NRAS, BRAF, APC, and CTNNB1) in these pathways are almost mutually exclusive [33,43]. Separate and combined analysis of these genes has been associated with RFS in MSI stable stage III patients, but not in MSI stable stage II patients [38,42]. Similar observations were done here in stage II, although MSI status was unknown in our study population.…”

Nuclear CD24 Drives Tumor Growth and Is Predictive of Poor Patient Prognosis

“…A transcriptional signature was developed and evaluated for its ability to stratify patient outcome as we have done before (29). We analyzed 4 bladder cancer (23–26) and 5 colorectal cancer (30–34) patient datasets with common microarray technology because of the relevance of CD24 in both bladder cancer (11) and colon cancer (15,35). We analyzed additional patient datasets, based on large sample sizes and common microarray platforms, for 3 other cancer types (36–38) for which we’ve confirmed the existence of nucCD24 (Fig.…”

Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer

“…Poor prognosis of APC- wt/MSS proximal tumours was validated in an independent patient cohort ( Marisa et al , 2013 ) using a predictor of APC -wt status from microarray expression data. Most previous studies evaluating APC mutation status have not identified a relationship with prognosis ( Dix et al , 1994 ; Conlin et al , 2005 ; Hsieh et al , 2005 ; Chen et al , 2009 ; Birnbaum et al , 2012 ). However, these studies did not consider CRC groups by tumour location and MSI status, likely precluded by their smaller sample sizes ( n =100–218), and only performed mutation screening for limited regions of the APC gene.…”

“…Although mutations in APC have a principal role in CRC initiation, their relation to outcome remains unclear. Most previous studies have not found an association between the presence of APC mutation and prognosis, but these analysed small patient cohorts, only screened limited regions of the APC gene, and did not account for prognostically important features such MSI, CIN, BRAF mutation and tumour location ( Dix et al , 1994 ; Løvig et al , 2002 ; Conlin et al , 2005 ; Hsieh et al , 2005 ; Meguid et al , 2008 ; Chen et al , 2009 ; Wong, 2010 ; Birnbaum et al , 2012 )…”