title: ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt.
abstract: 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.
  
  
  
  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).
  
  
  
  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 3.8×10-3& 4.6×10-3; 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.
  
  
  
  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.
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy, Beni-suef University, Beni-suef, Egypt; Clinical Pharmacy Department, Faculty of Pharmacy, Misr University for Science and Technology, Giza, Egypt.
authors.forename: Amira B
authors.initials: AB
authors.lastname: Kassem
authors.affiliation: Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Salem Eid
authors.initials: SE
authors.lastname: Salem
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Abdelrahim
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy, Beni-suef University, Beni-suef, Egypt.
authors.forename: Amira S A
authors.initials: AS
authors.lastname: Said
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salahuddin
authors.affiliation: Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Marwa Mahmoud
authors.initials: MM
authors.lastname: Hussein
authors.affiliation: Department of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Bahnassy
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004534:Egypt; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051759:Xeroderma Pigmentosum Group D Protein / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: CRC; ERCC1; ERCC2; Oxaliplatin; Survival