[Correlation of initial DNA damage detected by alkaline comet assay and clinical endpoints in lung cancer patients]

Cells derived from lung cancer are biological heterogeneous and have different intrinsic radiosensitivity, it is a key question for us to investigate radiosensitive parameters for an individualized radiotherapy plan. The comet assay is a sensitive and facilitated method to detect single-cell DNA damage and repair, and the results from it have been proven to be so highly coincident with those from clonogenic assay by cell-line investigations that it has been considered as a promising method in predicting radiosensitivity. The study is designed to evaluate preliminarily the correlation between initial DNA damage detected by alkaline comet assay and the clinical endpoints.

Biopsy samples from 31 lung cancer patients by fibrous bronchial endoscopy were detected by alkaline comet assay from April, 2002 to November, 2002. The adjusted tail moment (R TM) was measured and thoracic local-region lesions were measured by computer tomography scan. Response rate (RR) and time to progression (TTP) for the local-region lesions were as clinical endpoints. SPSS 10.0 software was used to compare median R TM of different RR and TTP groups by Mann-Whitney U and Kruskal-Wallis H rank test, the correlations between R TM with RR and TTP were estimated by Spearman's rank test.

There were no statistic differences of median R TM among different pathological types with a median R TM of 0.98, 1.27 and 1.05 in squamous cell carcinoma group, adenocarcinoma group and small cell lung cancer group, respectively (Chi-square=0.347, P=0.84). Through a median follow-up of 10 months, a median R TM of 1.08 and 1.21 for squamous cell carcinoma group and small cell lung cancer group in RR≥50% group was greater than 0.88 and 0.91 in RR < 50% group; median R TM in TTP > 9-monthgroups stratified according to pathological type was greater than that in TTP≤9-month groups (1.26, 1.38 and 1.39 versus 0.71, 0.48 and 1.03 for squamous cell carcinoma group, adenocarcinoma group and small cell lung cancer group respectively), but the differences of R TM classified by RR or TTP were not statistically significant (U=63.5, P=0.58; U=71, P=0.057); the Spearman's coefficients of R TM with RR and TTP were -0.105 (P=0.57) and 0.38 (P=0.035). The coefficients of R TM with TTP was 0.47 for non-small cell lung cancer indicating a modest correlation (P=0.048) and 0.043 for small cell lung cancer (P=0.89).

Although the results are confounded due to sampling and the greater background tail moments, Spearman's coefficient of R TM with TTP for non-small cell lung cancer indicates a modest positive correlation. The comet assay might be a promising method in predicting intrinsic radiosensitivity of lung cancer cells and techniques for sampling and assaying need to be further improved.