Introduction: Lung cancer has one of the highest mortality rates among all human cancers. Higher mortality has been noted in the past in men with the history of smoking but no significant differences in mortality exist in never smoking men and women. Some gender differences to date have been linked to genes located on sex chromosomes.

Methods: We quantified levels of 57 cytokines, chemokines and growth factors using multiplexed immunoassays to determine patterns of serum biomarkers in men and women with non-small cell lung cancer (NSCLC; 250 men, 116 women) and compared these with serum marker patterns in subjects with asthma (AST; 68 men, 132 women) and normal controls (NOR; 250 men, 116 women). Data were reduced using inter-pathology comparisons with statistical significance determined using the Kruskall-Wallis U test with p < 0.05 considered significant. Scalar sums of inter-pathology percentage differences (NSCLC vs. NOR, AST vs. NOR and NSCLC vs. AST) in marker expression were used for hierarchically ranking the markers. We selected markers based on at least one statistically significant difference was present for a given marker; those showing marginally significant differences were discarded.

Results: The markers showed unique gender- and disease specific patterns. For unisex analysis of NSCLC, we identified 36 markers with the 25% change cutoff threshold and 32 markers with the 50% cutoff. For women, we found 32 markers with the 25% cutoff and 30 with the 50% cutoff. For men, 39 markers were found at the 25% cutoff and 37 at the 50% cutoff. Expression of four markers was unique for women with NSCLC compared to NOR: IL-8 and serum amyloid P (downregulated), serum amyloid A and C-reactive protein (all upregulated). Five markers were unique for men with NSCLC compared to NOR: Insulin (downregulated), matrix metalloproteinases-7 and -8, resistin and hepatocyte growth factor (all upregulated). Three markers showed opposite patterns of expression; VEGF was downregulated in women and upregulated in men with NSCLC compared to NOR. Leptin was upregulated in women and downregulated in men and MIP-1α were upregulated in men and downregulated in women with NSCLC compared to NOR.

Conclusion: Our study has revealed surprisingly large qualitative and quantitative differences in biomarker expression patterns and levels in serum specimens from men and women suffering from NSCLC. The markers appear to be products of genes residing on several chromosomes and are not limited to sex chromosomes. Our findings may have implications for the diagnosis of non-small cell lung cancer, early detection of the disease through simple blood tests, characterization of disease progression and differentiation among the pathologies. It may find application in discovery and development of novel therapeutic strategies for human diseases.

Citation Information: Clin Cancer Res 2010;16(7 Suppl):B2