APOPTOSIS GENE EXPRESSION PROFILE IN EARLY-STAGE NON SMALL CELL LUNG CANCER
Metodieva SN1, Cherneva RV, Nikolova DN, Genchev GD, Petrov DB, Toncheva DI
*Corresponding Author: Svetlana Nikolova Metodieva, Department of Medical Genetics, Medical University Sofia, 2 Zdrave str, 1431 Sofia, Bulgaria; Tel.: +359-2-952-0357; Fax: +359- 2-952-0357; E-mail: svetlana.metodieva@yahoo.com
page: 47

INTRODUCTION

Lung cancer is the leading cause of cancerrelated death worldwide [1]. It is the most common cancer in men (1.1 million cases, 16.5% of total cases), while in females, lung cancer is the fourth most frequent cancer (513,000 cases, 8.5% of all cancers) [2]. In Bulgaria, the age-standardized incidence rates of lung cancer by sex per 100,000 population are 72 for men and 11.1 for women [1]. According to their histological type, 80-85% of lung cancer cases belong to non small cell lung cancers (NSCLC), of which 35-40% are adenocarcinomas (AC), 25-30% squamous cell carcinomas (SCC) and 10-15% large cell cancers [3]. Worldwide AC is more frequent than SCC in women (55% vs. 25%), compared to men (30% vs. 57%) [4], while in Bulgaria SCC is more frequent in both sexes: 25.9 vs. 17.0% for women and 41.9 vs. 6.3% for men [5]. Survival rates in NSCLC cases depend on the tumor stage at diagnosis, the 5-year survival rate of patients with resected NSCLC being between 50-60% [6,7]. The current tumor node metastasis (TNM) system remains inaccurate for prediction of individual patientsí survival, as 50% of patients with early-stage NSCLC will develop recurrent disease [8]. Thus, it is important to identify patients with the highest likelihood for recurrence who may potentially benefit the most from adjuvant chemotherapy. Assessment of a patientís prognosis could be improved by combining standard clinical variables such as tumor stage and histology with intrinsic genetic characteristics of the tumors. Apoptosis is an evolution-conserved and genetically regulated form of programmed cell death, which plays an important role in maintenance of tissue homeostasis. Resistance to apoptosis is a fundamental property of human cancers [9]. General resistance of NSCLC to a diversity of cytotoxic agents suggests a deregulation of apoptotic signaling [10]. Of clinical importance is the identification of novel prognostic markers for recurrence and patientsí stratification in early stages of the disease. We have analyzed the expression of 84 apoptosis regulators in a group of Bulgarian patients with early-stage NSCLC.



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