Genetic Fingerprint Concerned With Lymphatic Metastasis Of Human Lung Squamous Cancer

Objective: With the most recent introduction of microarray technology to biology, it becomes possible to perform comprehensive analysis of gene expression in cancer cell. In this study the laser microdissection technique,cDNA microarray analysis and immunohistochemistry were combined to obtain accurate molecular profiles of lymphatic metastasis in patients with lung squamous cell carcinoma.Methods: Primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients who underwent complete resection of lung cancer. According to the source of lung cancer cells, the samples were classified into three groups: the primary tumor with lymphatic metastasis (TxN+, n=5), the primary tumor without lymphatic metastasis (TxN-, n=5) and matched tumor cells from metastatic lymph nodes (N+, n=5). Total RNA was extracted from laser microdissected tumor samples. Adequate RNA starting material of mRNA from primary tumor or metastatic nodes were labeled and then hybridized into the same microarray containing 6 000 known, named human genes/ESTs. After scanning, data analysis was performed using GeneSpringTM6.2 software. Immunohistochemical staining was used to detect the expression of CCL20 and PLA2G2A in specimens.Results: A total of 37 genes were found to be able to separate TxN+ from TxN-. TxN+ has higher levels of genes concerned with structural protein, signal transducer, chaperone and enzyme. TxN- has higher levels of genes coding for cell cycle regulator, transporter, signal transducer and apoptosis regulator. Interestingly, there were no differentially expressed genes between N+ and TxN+. The expression of CCL20 in TxN- was higher than that in TxN+ (P<0.05). The expression of PLA2G2A in TxN- was higher than that in TxN+ (P<0.05), also.Conclusion: The acquisition of the metastatic phenotype might occur early in the development of lung squamous cancer. We raise the hypothesis that the gene-expression signature described herein is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis and to look for novel therapeutic targets.