Gene expression from bronchoscopy obtained tumour samples as a predictor of outcome in advanced inoperable lung cancer

Background

Several studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer.

Methods

Bronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B.

Results

More than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen’s κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p<0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p = 0.03, RR = 2.11) expression on overall survival in a group of 60 patients with NSCLC.

Conclusion

These results show the feasibility of multiple gene expression analysis in bronchoscopy obtained cancer specimens as prognostic markers in radiotherapy and chemotherapy for advanced lung cancer. A limiting factor was relatively high proportion of samples from which sufficient amount of RNA could not be isolated.