
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
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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 patients’ 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 patient’s 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 patients’
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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