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ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt.
- Source :
-
Experimental and molecular pathology [Exp Mol Pathol] 2017 Feb; Vol. 102 (1), pp. 78-85. Date of Electronic Publication: 2017 Jan 12. - Publication Year :
- 2017
-
Abstract
- Background: The impact of Excision repair cross-complementation group 1 (ERCC1) and group 2 (ERCC2) expression levels on the efficacy of oxaliplatin-based chemotherapy is still controversial. The present study was conducted to determine the predictive value of these molecular biomarkers in stage III and IV colorectal cancer (CRC) patients receiving oxaliplatin (OX)-based chemotherapy as first-line treatment.<br />Methods: The study included 80 CRC patients who received first line oxaliplatin based chemotherapy The expression levels of ERCC1 and ERCC2-mRNA and proteins were determined in the primary tumors by quantitative real time reverse transcription polymerase chain reaction(RT-qPCR) and immunohistochemistry (IHC); respectively. The results of mRNA expression were correlated with patients' characteristics, response to treatment, overall- and event free survival (OS & EFS).<br />Results: Sixty four out of the 80 patients were legible for assessment of ERCC1 and ERCC2 expression. The cut-off levels of ERCC1and ERCC2-RNA were 3.8×10 <superscript>-3</superscript> & 4.6×10 <superscript>-3</superscript> ; respectively. Reduced ERCC1 and ERCC2 RNA expressions were detected in 50 (78.1%) and 48 (75%) cases, respectively whereas reduced proteins were detected in 48 cases (75%) for ERCC1 and ERCC2. After The median follow up period was 30.5months (range: 7-104months), Patients with low mRNAERCC1levels showed significantly longer OS (p=0.011) and EFS (p˂0.001). However, no significant relation was found between ERCC2 levels and OS or EFS. In multivariate analysis performance status (PS), stage of the disease and ERCC1-mRNA expression were independent prognostic factors for EFS whereas tumor histology and stage of the disease were independent factors for OS.<br />Conclusions: ERCC1 expression levels may help in selecting patients who benefit from oxaliplatin chemotherapy in stage III & IV CRC. Further large trials are needed to validate these data.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Biomarkers, Tumor biosynthesis
Colorectal Neoplasms pathology
DNA-Binding Proteins biosynthesis
Egypt
Endonucleases biosynthesis
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic drug effects
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Neoplasm Staging
Organoplatinum Compounds administration & dosage
Outcome Assessment, Health Care methods
Outcome Assessment, Health Care statistics & numerical data
Oxaliplatin
Proportional Hazards Models
Reverse Transcriptase Polymerase Chain Reaction
Xeroderma Pigmentosum Group D Protein biosynthesis
Young Adult
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Biomarkers, Tumor genetics
Colorectal Neoplasms drug therapy
DNA-Binding Proteins genetics
Endonucleases genetics
Xeroderma Pigmentosum Group D Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0945
- Volume :
- 102
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental and molecular pathology
- Publication Type :
- Academic Journal
- Accession number :
- 28088319
- Full Text :
- https://doi.org/10.1016/j.yexmp.2017.01.006