Gene-expression Profiling in Non-small Cell Lung Cancer with Invasion of Mediastinal Lymph Nodes for Prognosis Evaluation.

Background/Aim: The aim of the study was to determine the pathways and expression profile of the genes that might predict response to neoadjuvant chemotherapy in patients with stage IIIA non-small cell lung cancer (NSCLC). Materials and Methods: We evaluated, by microarray, the gene-expression profile of tumoral mediastinal lymph node samples surgically removed from 27 patients with stage IIIA NSCLC before neoadjuvant chemotherapy treatment. Depending on the response to the induction treatment, the patients were divided in two groups: group A: patients whose disease evolved, stabilized or who had minor response to chemotherapy, and group B: patients whose disease stabilized or had major response to chemotherapy. Results: The microarray experiments identified 1,127 genes with a modified expression in the tumoral tissue compared to normal tissue with p≤0.05 and 44 genes with p≤0.01. The identified up-regulated genes between tumoral versus normal tissue included collagen, type I, alpha 1 (COL1A1), inhibin beta A (INHBA) and thioredoxin interacting protein (TXNIP). Pathways identified with a false-discovery rate of <0.005 included: cytokine pathways, focal adhesion or extracellular matrix receptor interaction. Conclusion: Our approach identified important characteristics of NSCLC and pointed- out molecular differences between sub-groups of patients based on their response to therapy. The ultimate aim of reducing the high mortality rate in lung cancer is related to an increased efficiency of prevention/determination of cancer risk factor strategies and early detection of lung cancer while still in a curable stage. The major risk factors for lung cancer occurrence are smoking and high air pollution in large cities (1). Despite prevention campaigns and improved survival during the past two decades, lung cancer still represents the second leading cause of disease from cancer and the highest cancer-related death rate in Western countries. Approximately 55-60% of patients are diagnosed with disease in incurable stages, with distant metastases. Therefore, the 5-year survival rate considering all stages is only 13-16%. Non-small cell lung cancer (NSCLC) represents the most frequent type of bronchial tumor. It is classified into two major histological sub-types: adenocarcinoma and squamous cell carcinoma. Both sub-types are very different in regard to copy number, DNA methylation, genetic mutations, transcriptome, proteome and biomarkers. Defining different lung cancer entities based on clinical, pathological and molecular alterations also determines disease evolution and treatment options. In spite of significant progress in the development of targeted-therapy, the high mortality rate in lung cancer firmly emphasizes the need for prevention and efficient detection of lung cancer, as well as a better classification, enabling patients to benefit from more specific therapy. Microarrays have been used for more than two decades in pre-clinical research to determine gene-expression profiling associated with different pathological sub-groups or diverse clinical evolution and to evaluate biological and cellular functions determined by these gene panels. In NSCLC with invasion of mediastinal lymph nodes (N2+), the currently accepted treatment attitude is a multimodal approach, based on platinum salts chemotherapy, followed by complete surgical resection for the patients that