Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients.

BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Dose-related effect of urinary cotinine levels on pulmonary function among Korean women.

SETTING: Country-wide general population in South Korea. BACKGROUND: The dose-response relationship between smoking and pulmonary function in women may have been significantly over-estimated by studies that employed a self-reporting questionnaire. OBJECTIVE: To evaluate whether this relationship was still observed among Korean women when smoking levels were determined by urinary cotinine measurements. DESIGN: A total of 4584 Korean women from the spirometry data set of the Korean National Health and Nutrition Examination Surveys IV and V (2008-2010) were included. Analysis of covariance was performed to estimate the dose-related effect of urinary cotinine levels on pulmonary function after adjusting for covariates in this country-wide cross-sectional study. RESULTS: Compared to urinary cotinine levels (cut-off 50 ng/ml), the false-positive rate of self-reported smoking was 53.2%. After the smokers were divided into deciles, the regression coefficients for percentage forced expiratory volume in 1 second (FEV1%) and percentage forced expiratory volume/forced volume capacity (FEV1/FVC) ratio (FEV1/FVC%) were -0.2903 and -0.2680 (%/decile), respectively (both P < 0.001). CONCLUSION: It is necessary to use objective methods when determining the smoking status of Korean women. Even after reducing information bias, smoking affected pulmonary function in a dose-dependent manner.

Relationship between T-lymphocyte subsets and suppressor cell activity in patients with chronic active hepatitis B.

Thirty-nine patients with chronic HBV infection and 38 normal persons were investigated by simultaneous assay of T suppressor cell function and enumeration of T-lymphocyte subsets by monoclonal antibodies. In patients with chronic active hepatitis B (CAH-B), T suppressor cell activity (17.8 +/- 8.8%) was significantly lower than in healthy HBsAg carriers (35.4 +/- 12.3%) and normal control persons (38.3 +/- 16.3%). The proportions of T-lymphocyte subsets in patients with CAH-B were not different from those of healthy HBsAg carriers and control persons. No correlation was observed in between percentage suppression and proportions of T-lymphocyte subsets. These findings suggest that in the absence of a simultaneous assay of function, enumeration of T-lymphocyte subsets by using monoclonal antibodies is an inadequate assessment of immune regulation.