Abstract
ObjectiveThis meta-analysis aimed to comprehensively examine the relationship between the clinicopathological and demographical characteristics and ALK rearrangements in patients with non-small cell lung cancer (NSCLC).Methods and Main FindingsIn total, 62 qualified articles including 1178 ALK rearranged cases from 20541 NSCLC patients were analyzed, and the data were extracted independently by two investigators. NSCLC patients with ALK rearrangements tended to be younger than those without (mean difference: −7.16 years; 95% confidence interval (95% CI): −9.35 to −4.96; P<0.00001), even across subgroups by race. Compared with female NSCLC patients, the odds ratio (OR) of carrying ALK rearrangements was reduced by 28% (95% CI: 0.58–0.90; P = 0.004) in males, and this reduction was potentiated in Asians, yet in opposite direction in Caucasians. Likewise, smokers were less likely to have ALK rearrangements than never-smokers (OR = 0.33; 95% CI: 0.25–0.44; P<0.00001), even in race-stratified subgroups. Moreover, compared with NSCLC patients with tumor stage IV, ALK rearrangements were underrepresented in those with tumor stage I–III (OR = 0.58; 95% CI: 0.44–0.78; P = 0.0002). Patients with lung adenocarcinomas had a significantly higher rate of ALK rearrangements (7.2%) than patients with non-adenocarcinoma (2.0%) (OR = 2.25; 95% CI: 1.54–3.27; P<0.0001).ConclusionOur findings demonstrate that ALK rearrangements tended to be present in NSCLC patients with no smoking habit, younger age and tumor stage IV. Moreover, race, age, gender, smoking status, tumor stage and histology might be potential sources of heterogeneity.
Highlights
Lung cancer is the leading cause of cancer deaths worldwide
Our findings demonstrate that anaplastic lymphoma kinase (ALK) rearrangements tended to be present in Non-small cell lung cancer (NSCLC) patients with no smoking habit, younger age and tumor stage inverse variance (IV)
Qualified articles Based on the search strategy, a total of 20541 NSCLC patients were analyzed from 62 qualified articles [4,8,11,12,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74], and of them 1178 patients (5.7%) had ALK rearrangements. 43 of 62 articles were conducted in Asians (19 in Chinese, 13 in Japanese, 10 in Koreans and 1 in Indians), 12 articles in Caucasians (7 in Americans and 5 in Europeans) and 7 articles in multi-ethnic populations. 43 articles involved unselected populations [4,8,11,12,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55], and 20 articles enrolled specific groups of NSCLC patients according to either clinicopathological characteristics or genetic makeup [46,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74], with one article [46] provided data from both unselected and selected NSCLC groups
Summary
Lung cancer is the leading cause of cancer deaths worldwide. Most of lung cancer patients are diagnosed at an advanced stage with extremely poor prognoses. In 2007, Soda and colleagues first identified a tyrosine kinase as a promising therapeutic target and diagnostic molecular marker for NSCLC, and this kinase accelerates the formation of a fusion gene comprising the portions of echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) in NSCLC cells [2]. This formation is biologically important as EML4 activates ALK kinase via mediating ligand-independent oligomerization of ALK [3,4], and the activated ALK is responsible for the growth and survival of lung cancer cell lines, the process being highly sensitive to ALK kinase inhibitors [5]. There is an urgent need to synthesize available articles by means of a meta-analysis to comprehensively examine the relationship between the clinicopathological and demographical characteristics and ALK rearrangements in NSCLC patients
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