Abstract
As the current staging system is imprecise for estimating prognosis of early stage non-small cell lung cancer (NSCLC), it is important to identify other methods for selecting high-risk patients after failed surgical treatment. The aim of the study was to evaluate the expression of 23 genes as putative prognostic markers in early stage NSCLC. The study was performed on 109 pairs of tumor and matched unaffected lung tissue surgical specimens taken from stage I and II NSCLC patients. We evaluated the mRNA level of 23 genes using the real-time PCR method. The difference in the expression between the tumor and normal tissue for each gene was analyzed using a general linear model. The influence of gene expression on survival was analyzed by using the proportional hazards model. Eighteen out of the 23 genes showed statistically significant differences in expression between the tumor and non-tumor tissue. For 12 genes (ITGB1, ITGB3, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, CXCR3, CXCR4, TNF, CHKA, AGFG1, and CTC1), the expression was lower, and for six genes (ITGA5, IL8, IL6, CXCL2, CXCL3, and CXCL12), it was higher in the tumor tissue as compared to the matched normal tissue. Expression changes were more pronounced in squamous cell carcinomas than in adenocarcinomas or large cell carcinomas. Of all the analyzed genes, only CXCL5 was found to statistically significantly (p = 0.04) influence both overall and disease-free survival. Among the 23 genes previously suggested to be relevant for early staged NSCLC patients’ postoperative outcome, only CXCL5 showed a statistically significant prognostic effect.
Highlights
Lung cancer is the most common cause of cancer deaths worldwide, and approximately 80 % of the patients have non-small cell lung cancer (NSCLC)
The genes used for evaluation were defined according to a number of microarray-based studies, comprehensive real-time PCR analyses, and/or protein-evaluating assays [6,7,8,9,10,11,12,13,14,15,16,17]
The study was performed on 109 pairs of tumor and matched unaffected lung tissue specimens obtained from early stage NSCLC patients who underwent a curative surgery at the Bialystok Medical University Hospital
Summary
Lung cancer is the most common cause of cancer deaths worldwide, and approximately 80 % of the patients have non-small cell lung cancer (NSCLC). Current mode of lung cancer therapy mainly depends on the TNM disease staging and tumor histological classification, and the treatment-ofchoice for early stage NSCLCs constitutes radical surgery. About 30 to 50 % of early stage NSCLC patients (in stages I and II) die within 5 years after radical surgical treatment as a consequence of disease recurrence or metastasis. Results of recent studies have shown some benefit of adjuvant chemotherapy in surgically treated NSCLC patients with 5-year survival advantage of 4–15 % [1]. Based on the results of high-throughput microarray and real-time PCR data, several prognostic gene expression signatures have been created to stratify patients for appropriate treatment; the proposed gene sets differ significantly from one another. Further studies on gene expression signature as well as verification of previously reported data have to be performed [3]
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