A Predictive Genetic Signature for Response to Fluoropyrimidine-Based Neoadjuvant Chemoradiation in Clinical Stage II and III Rectal Cancer
| Autor: | Conor P. Delaney, Wendy Louise Allen, Jason Chan, Miika Ahdesmaki, Huankai Hu, Steve Deharo, Harry L. Reynolds, Michael T. Kinsella, Andrea McCulla, P.G. Johnston, Joseph Willis, Timothy J. Kinsella |
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| Rok vydání: | 2013 |
| Předmět: |
Oncology
medicine.medical_specialty Cancer Research Colorectal cancer Gene regulatory network UBC Bioinformatics ubiquitination lcsh:RC254-282 03 medical and health sciences gene array 0302 clinical medicine Internal medicine Medicine STAT1 Gene Pathological 030304 developmental biology Original Research 0303 health sciences biology business.industry Microarray analysis techniques ubiquination EHBP1 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease rectal neoplasms 3. Good health Fluorouracil 030220 oncology & carcinogenesis biology.protein DNA microarray business medicine.drug |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 3 (2013) |
| ISSN: | 2234-943X |
| Popis: | PurposePreoperative chemoradiation is currently the standard of care for patients with clinical stage II and III rectal cancer but only about 45% of patients achieve tumor downstaging and less than 20% of patients achieve a pathologic complete response. Better methods to stratify patients according to potential neoadjuvant treatment response are needed. We used microarray analysis to identify a genetic signature that correlates with a pathological complete response to neoadjuvant chemoradiation. We performed a gene network analysis to identify potential signaling pathways involved in determining response to neoadjuvant treatment.Patients and MethodsWe identified 31 T3-4 N0-1 rectal cancer patients who were treated with neoadjuvant fluorouracil-based chemoradiation. 8 patients were identified to have achieved a pathological complete response to treatment while 23 patients did not. mRNA expression was analyzed using cDNA microarrays. The correlation between mRNA expression and pathological complete response from pre-treatment tumor biopsies was determined. Gene network analysis was performed for the genes represented by the predictive signature.ResultsA genetic signature represented by expression levels of the 3 genes EHBP1, STAT1, and GAPDH was found to correlate with a pathological complete response to neoadjuvant treatment. The difference in expression levels between patients who achieved a pathological complete response and those who did not was greatest for EHBP1. Gene network analysis showed that the 3 genes can be connected by the gene UBC. ConclusionThis study identifies a 3-gene signature expressed in pre-treatment tumor biopsies that correlates with a pathological complete response to neoadjuvant chemoradiation in patients with clinical stage II and III rectal cancer. These 3 genes can be connected by the gene UBC, suggesting that ubiquination is a molecular mechanism involved in determining response to treatment. Validating this genet |
| Databáze: | OpenAIRE |
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