Abstract
Simple SummaryLung cancer is the leading cause of cancer-related death worldwide. Although novel therapy regimens using immuno- and targeted therapy have improved survival for a subgroup of patients with lung cancer, the five-year survival rate is still poor. The inhibitor of apoptosis protein (IAP) family represents a heterogeneous group of anti-apoptotic proteins that are highly expressed in a variety of human malignancies. Despite conflicting results regarding the prognostic significance of IAPs, high expression of some members of this family have been extensively reported to be associated with poor prognosis in lung cancer patients. Therefore, there might be a subgroup of patients that could benefit from a targeted therapy against specific IAP family members in lung cancer. The aim of this study was to perform a meta-analysis to investigate the prognostic value of IAP family members and their association with clinicopathological features in lung cancer.Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% is non-small-cell and 15% is small-cell lung cancer. The inhibitor of apoptosis proteins (IAPs) represent a heterogeneous family of anti-apoptotic proteins, some members of which have been reported to correlate with clinical outcome in lung cancer. We screened PubMed, Web of Science, and Scopus for studies that investigated the prognostic value and clinicopathological features of IAPs in lung cancer. Forty-five eligible studies with 4428 patients assessed the expression of the IAPs survivin, XIAP, livin, and BRUCE. The pooled hazard ratio (HR) of 33 studies that analyzed overall survival (OS) revealed a positive correlation between survivin expression and poor prognosis. Seven studies displayed a strong association between survivin and disease recurrence. Two studies that assessed the expression of XIAP and livin, respectively, proved a significant relationship of these IAPs with poor OS. Meta-analyses of clinicopathological variables revealed a significant association between survivin and T stage, UICC stage, the presence of lymph node metastasis, and grade of differentiation. In conclusion, high expression of distinct IAPs significantly correlates with prognosis in lung cancer. Therefore, lung cancer patients might benefit from a targeted therapy against specific IAPs.
Highlights
Lung cancer is the most common cause of cancer-related death worldwide [1]
By meticulously reading the abstracts, we identified 133 studies that focused on the expression of the inhibitor of apoptosis proteins (IAPs) family members survivin, XIAP, livin, and BRUCE
We analyzed whether expression levels of the investigated IAP family members survivin, livin, XIAP, and BRUCE were associated with survival in patients with lung cancer
Summary
Lung cancer is the most common cause of cancer-related death worldwide [1]. According to the World Health Organization (WHO) and International Association for the Study of Lung Cancer (IASLC), lung cancer can be classified as small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) [2,3,4]. In NSCLC cases with EGFR mutations, approximately 90% harbor an exon 19 deletion or exon 21 L858R mutation, which renders the tumors sensitive to EGFR TKIs [13,14,15,16,17]. Due to their increased benefit on progression-free survival (PFS) and mild adverse effects, certain FDA- (US Food and Drug Administration) and EMA- (European Medicines Agency) approved EGFR TKIs such as erlotinib and gefitinib are usually implemented as first-line therapy for patients with advanced NSCLC [14,17,18,19]. A dual EGFR-VEGF pathway inhibition (e.g., erlotinib and bevacizumab or erlotinib and ramucirumab) has been reported as a promising strategy for patients with EGFR-mutant NSCLC [13]
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