Potential biomarkers for the prediction and prognosis of patients with NSCLC

Introduction

Worldwide, lung cancer is the most common cause of death for both men and women associated with cancer and credited with 1.38 million deaths annually. It is therefore necessary to identify biomarkers that could be related to the prediction of treatment response in patients with lung cancer and also helped in the prognosis of the disease. The main types of lung cancer are non small cell lung cancer and small cell type. This distinction is important because the different treatment; non-small cell lung cancer (NSCLC) is sometimes treated surgically, while the small cell lung carcinoma (SCLC) usually has a better response to treatment with chemotherapy and radiotherapy. About 85% to 90% of lung cancers are non-small cell lung cancer (NSCLC). There are 3 main subtypes of NSCLC - squamous cell (epidermoid) carcinoma, adenocarcinoma and large cell (undifferentiated) carcinoma. For our purposes, we decided to use only the basic division of NSCLC into adenocarcinoma and nonadenokarcinoma.

Materials/methods

In our study, we investigated a group of 228 patients with NSCLC treated surgically (70/228) or with an adjuvant regimen consisting mostly of a combination of platinum derivatives and vinorelbine (158/228). For the investigation, formalin-fixed paraffin embedded (FFPE) tissue samples were used. Using the FISH method, the status of EGFR, C-MYC, FGFR, C-MET, the presence of rearrangements in ALK and ROS1 genes, and the number of copies of chromosomes 7 and 8 were determined. Concurrently, the qPCR method was used to investigate the mutational status in the K-RAS and B-RAF genes.

Results and conclusions

Statistical analyses of the clinical and laboratory results were performed. Of course we appeared many expected correlations as significant (stage versus OS, DFS, CSS; C-MYC versus CEP8 etc.). Histologicaly, the percentage of women in the group of adenocarcinomas was higher than in nonadenocarcinomas. Also the patients in adenocarcinoma group were younger. When we correlated each marker with histological type, we found out, that the percentage of amplified EGFR was higher in adenocarcinomas while the percentage of gain of ALK copy number (similarly for C-MYC) was higher in nonadenocarcinoma histotype. We also revealed that the cells with some change tend to polysomy - correlations between CEP7 and CEP8, CEP7 and FGFR, CEP8 and ROS1, ROS1 and C-MYC, CEP7 and C-MYC, ROS1 and FGFR - in these cases a gain of one gene/ chromosome was accompanied by gain(s) of another gene(s)/ chromosome(s). We evaluated also impact of our markers to survival. The only statisticaly significant marker was the presence of disrupted ROS1 gene. In seems to be a poor prognostic factor for OS. Other correlations with OS were not found.