Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of microsatellite stable stage III Colorectal Adenocarcinoma (MSS-CRC) with wild type or mutant p53 to study the prognostic significance of the mutation


ABSTRACT: Clinical Significance: Understanding the differences in colorectal cancer (CRC) aggressiveness and clinical outcomes in relation to tumor stage and different molecular subsets is at most important for designing treatment regimens. However, molecular signatures for specific phenotypic subsets that predict the aggressiveness and clinical outcomes of CRC, specifically in advanced disease stage are lacking. Therefore, for the first time, the current study has identified a set of molecular markers that are associated with aggressive Stage III CRCs that exhibited microsatellite stable and mutant p53 phenotypic features. These findings might aid in designing aggressive treatment regimens and help to provide insights into the development of novel therapeutic targets. Results: Increased incidence of p53 mutations in MSS CRCs (58%) was associated with higher CRC-specific mortality than MSS-p53 wild-type phenotypes (log-rank, P=0.025; and hazard ratio, 2.52; 95% confidence interval, 1.25-5.08). Of 49 down-regulated genes, LPAR6, PDLIM3 and PLAT and of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8, were confirmed by qNPA, qRT-PCR, and IHC platforms. Conclusions: p53 mutations are associated with poor prognosis of Stage III microsatellite stable CRCs. p53 wild type vs. mutant tumor samples

ORGANISM(S): Homo sapiens

SUBMITTER: Dongquan Chen 

PROVIDER: E-GEOD-27157 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas.

Katkoori Venkat R VR   Shanmugam Chandrakumar C   Jia Xu X   Vitta Swaroop P SP   Sthanam Meenakshi M   Callens Tom T   Messiaen Ludwine L   Chen Dongquan D   Zhang Bin B   Bumpers Harvey L HL   Samuel Temesgen T   Manne Upender U  

PloS one 20120119 1


Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite  ...[more]

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