14-3-3 σ (σ) methylation (M) in pre-treatment serum DNA of cisplatin (cis)/gemcitabine (gem)-treated non-small-cell lung cancer (NSCLC).

7042 Background: σ is a major G2/M checkpoint control gene, and disruption of its function increased DNA damage caused by irradiation and adriamycin in human cells. σ hypermethylation has been associated with loss of expression in several tumors.,To determine whether σ Μ in acellular serum DNA could predict survival with gem/cis in stage IV NSCLC patients (p), we analyzed serum from blood drawn from NSCLC p before chemotherapy administration and correlated results with clinical outcome. From 1 August 2001 to 30 June 2002, 115 p were included and treated with cis 75 mg/m, d 1, plus gem 1000 mg/m, d 1, 8, every three weeks. Ten ml of blood were used for σ M analysis. p characteristics: 62 years (range, 31-81); male, 108 (93.9%); ECOG performance status (PS): 0, 32 (27.8%), 1, 83 (72.2%); smokers, 99 (86.1%); adenocarcinoma, 51 (44.7%), squamous cell carcinoma, 42 (36.8%), large cell carcinoma, 21 (18.4%).,39 p were σ M-positive (+) and 76 M-negative (-). Median survival (MS) was 9.87 months (mos) (95% CI, 7.3-12.59) for the M- group, compared to 15.13 mos (95% CI, 9.7-20.6) for the M+ group (P=0.0047). Survival hazard ratio (HR) for σ M- status was 2.07 (95% CI, 1.24-3.45; P=0.006). MS for 22 σ Μ+ responders has not been reached, while for 29 σ M- responders, it was 11.32 mos (95% CI, 9.09-13.54) (P=0.0017). M- responders had a four times greater risk of death than M+ responders (HR = 3.95 [95% CI, 1.57-9.94]; P=0.004).,σ M analysis in serum offers a novel and accurate method to predict survival in responders to platinum-based chemotherapy. No significant financial relationships to disclose.