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Clinical Applications of Molecular Profiling in Colorectal Cancer

Kheirelseid, Elrasheid Ahmed Hassan
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Publication Date
2011-06
Keywords
Colorectal cancer, Molecular profiling, Gene expression
Type
Thesis
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Abstract
Despite developments in diagnosis and treatment, 20% of colorectal cancer (CRC) patients present with metastatic disease and 30% of cases recur after curative surgery. Furthermore, the molecular factors involved in prognosis and response to therapy in CRC are poorly understood. The objectives of this study were to examine the expression patterns of candidate miRNAs and mRNAs and proteins in CRC in order to identify molecular biomarkers for disease classification and prognostication. Expression patterns of miRNA and mRNA species were determined in FFPE and fresh colorectal tissues by microarray analysis and real-time quantitative PCR. Protein expression was determined by immunohistochemistry. Statistical analysis and correlation with clinicopathological data was performed using SPSS software. MiRNA signatures predictive of response of rectal cancer to neoadjuvant therapy were determined. Expression levels of CXCL12 (p=0.000), CDH17 (P=0.026), MUC2 (p=0.000), L-FABP (p=0.000) and PDCD4 (p=0.000) were down regulated and IL8 (p=0.000) was upregulated in tumours compared to normal colorectal tissues. Moreover, significant associations of gene expression levels and clinicopathological variables such as tumour size, grade, invasion and lymph node status were identified. Of further interest, significant miRNA/mRNA correlations were also determined in this study. A comprehensive list of biomarkers with highly differential expression patterns in colorectal cancer that could serve as molecular markers to complement existing histopathological factors in diagnosis, follow up and therapeutic strategies for individualised care of patients. Furthermore, the significant miRNA/mRNA correlations highlight important novel mechanisms in CRC initiation and progression.
Funder
National Breast Cancer Research Institute
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
cbn
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University of Galway Theses (PhD Theses)