Expression profile of genes in non-small cell lung carcinomas from long-term surviving patients.

Abstract

Non-small cell lung cancer (NSCLC) is usually associated with a poor prognosis. Some patients survive their disease, and the underlying molecular mechanisms are still poorly understood. The purpose of this investigation was to evaluate expression profiles of proteins determining the survival of NSCLC patients for 5 years. The expression of 21 gene products was evaluated immunohistochemically in paraffinembedded primary NSCLCs from 216 patients. The data were correlated with the survival times of the patients (survival of more or less than 5 years) by means of chi(2) test and hierarchical cluster analysis. The relationships of patients' survival and 21 parameters were determined including oncogene and tumor suppressor products and proliferative, apoptotic, and angiogenic factors. FOS, P53, RAS, ERBB1, JUN, PCNA, cyclin A, FAS/CD95, and HIF-1beta revealed a correlation to survival. In a second step, these nine parameters were further analyzed by hierarchical cluster analyses of all patients, of stage III patients, and of patients with squamous cell lung carcinomas. We identified clusters with significantly more long-term survivors. The expression of FOS, JUN, ERBB1, and cyclin A or PCNA were decreased in carcinomas of patients with long-term survival. The expression profile of these factors predicts a significantly better long-term outcome of NSCLC patients. This may have implications for the development of individualized therapy options in the future.