title: Monitoring of cyclooxygenase-2 levels can predict EGFR mutations and the efficacy of EGFR-TKI in patients with lung adenocarcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation detection has become a routine molecular test with significant implications for prognosis and therapeutic options of EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, acquiring sufficient amounts of tissue for analyzing EGFR mutations is not often feasible, and not all the patients with sensitive EGFR mutations have benefit from EGFR-TKI treatment.
  
  
  METHODS
  EGFR mutations were detected by amplification refractory mutation system (ARMS) in 44 patients of newly diagnosed lung adenocarcinoma, and patients with EGFR-positive mutations received EGFR-TKI treatment. The serum cyclooxygenase-2 (COX-2) levels were tested before EGFR-TKI treatment and on the 30th days after EGFR-TKI treatment.
  
  
  RESULTS
  Twenty-nine cases were detected EGFR mutations. EGFR mutation rate of serum COX-2 high-level group was significantly higher than low-level group (92.9% vs. 53.3%, P=0.025). Multivariate analysis showed that serum COX-2 level was independently associated with EGFR mutation (P=0.033, OR=12.385, 95%CI, 1.231-124.567). Analysis of the correlation between clinical characteristics and the response of EGFR-TKI showed that the serum COX-2 high-level group had a better efficacy than low-level group (P=0.000), and multivariate logistic regression analysis showed that the serum COX-2 level was the independently influencing factor (P=0.004). Kaplan-Meier analysis showed that patients of COX-2 high-level group have longer progression-free survival (PFS, P=0.013), and the Cox regression analysis showed that the same result (P=0.003; OR=0.980, 95% CI, 0.967-0.993).
  
  
  CONCLUSIONS
  The serum COX-2 level seems to be closely associated with EGFR mutations in patients with Lung adenocarcinoma. The serum COX-2 level could help us to predict the responses of EGFR-TKI and the PFS in patients harboring EGFR mutation.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang 832000, P. R. China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang 832000, P. R. China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang 832000, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang 832000, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang 832000, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000097:blood*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cyclooxygenase-2; EGFR mutation; lung adenocarcinoma; prognosis