The association between fibroblast growth factor receptor 1 gene amplification and lung cancer: a meta-analysis.

INTRODUCTION: Identifying target oncogenic alterations in lung cancer represents a major development in disease management. We examined the association of fibroblast growth factor receptor 1 (FGFR1) gene amplification with pathological characteristics and geographic region. MATERIAL AND METHODS: We conducted a meta-analysis of studies published between January 2010 and October 2016. Relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated regarding the rate of FGFR1 amplification in different lung cancer types and geographic region. RESULTS: Twenty-three studies (5252 patients) were included. There was heterogeneity between studies. However, in subgroup analyses for squamous cell carcinoma (SCC), small cell lung cancer (SCLC), studies using the same definition of FGFR1 amplification, and those from Australia, no significant heterogeneity was detected. The prevalence of FGFR1 amplification in these studies ranged from 4.9% to 49.2% in non-small cell lung cancer (NSCLC), 5.1% to 41.5% in SCC, 0% to 14.7% in adenocarcinoma, and 0% to 7.8% in SCLC. The prevalence of FGFR1 amplification was significantly higher in SCC than in adenocarcinoma (RR = 5.2) and SCLC (RR = 4.2). The prevalence of FGFR1 amplification ranged from 5.6% to 22.2% in Europe, 4.1% to 18.2% in the United States, 7.8% to 49.2% in Asia, and 14.2% to 18.6% in Australia. The rate of FGFR1 amplification was higher in Asians than in non-Asians (RR = 1.9) in NSCLC. CONCLUSIONS: These results suggest that FGFR1 amplification occurs more frequently in SCC and in Asians. FGFR1 amplification may be a potential new therapeutic target for specific patients and lung cancer subtypes.

Analysis of the Clinicopathological Characteristics and Risk Factors in Patients with Lung Cancer and Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To investigate the clinicopathological characteristics and risk factors in patients with lung cancer and COPD. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 282 patients with lung cancer, including 174 and 108 patients with and without COPD, respectively. Information on age, sex, smoking status, and histologic type was obtained from medical records. RESULTS: Lung cancer patients with COPD and those with the chronic bronchitis (CB) phenotype had higher smoking indices compared to those without COPD (723.95 ± 631.48 and 920.95 ± 712.93 versus 418.40 ± 506.84; P = 0.010; P = 0.001, resp.), and current smokers accounted for significantly higher proportions of lung cancer patients with COPD and the CB phenotype versus without COPD (51.15% and 63.74% versus 35.19%; P = 0.009; P = 0.001, resp.). Adenocarcinoma was significantly more common in lung cancer patients without versus with COPD (48.15% versus 35.63%; P = 0.037), whereas small cell lung cancer was more common in patients with COPD (23.56% versus 13.89%). Among patients with COPD, male sex (odds ratio [OR], 19.946; P < 0.001), current smokers (OR: 6.588; P = 0.001), and age ≥ 75 years (OR: 2.670; P = 0.008) were identified as high-risk factors. CONCLUSION: The risk factors for COPD among lung cancer patients were age ≥ 75 years, current smokers with the CB phenotype, and male sex.

Fibroblast Growth Factor Receptor 1 Gene Amplification in Nonsmall Cell Lung Cancer.

OBJECTIVE: To review the prevalence and prognostic significance of fibroblast growth factor receptor 1 (FGFR1) amplification and to establish an association between FGFR1 amplification and the clinical characteristics of nonsmall cell lung cancer (NSCLC). DATA SOURCES: We searched PubMed for English-language studies published between January 2010 and May 2016. STUDY SELECTION: We included all relevant articles, with no limitation of study design. RESULTS: FGFR1 amplification was reported in 8.7-20.0% of NSCLC cases and was significantly more frequent in squamous cell carcinomas (SCCs) (9.7-28.3%) than in adenocarcinomas (ADCs) (0-15.0%). The rates of FGFR1 amplification were as follows: males, 13.9-22.1%; females, 0-20.1%; Stage I NSCLC, 9.3-24.1%; Stage II NSCLC, 12.9-25.0%; Stage III NSCLC, 8.2-19.5%; Stage IV NSCLC, 0-12.5%; current smokers, 13.3-29.0%; former smokers, 2.5-23.0%; and nonsmokers, 0-22.2%. Overall survival was 43.9-70.8 months in patients with FGFR1 amplification and 42.4-115.0 months in patients with no FGFR1 amplification; disease-free survival was 22.5-58.5 months and 52.4-94.6 months, respectively. CONCLUSIONS: FGFR1 amplification is more frequent in SCCs than in ADCs. The association between FGFR1 amplification and clinical characteristics (gender, smoking status, and disease stage) and the prognostic significance of FGFR1 amplification in NSCLC remain controversial.

MicroRNA-138 negatively regulates non-small cell lung cancer cells through the interaction with cyclin D3.

Previous studies demonstrate that microRNA-138 (miR-138) is critical in non-small cell lung cancer (NSCLC) regulation. We further explored the molecular mechanism of miR-138 in NSCLC. Lentivirus was used to upregulate miR-138 in NSCLC cell lines H460 and SPC-A1 cells. Previously known effects of miR-138 upregulation on NSCLC, proliferation, cell cycle division, and cisplatin sensitivity were examined in H460 and SPC-A1 cells. Moreover, previously unknown effect of miR-138 upregulation on NSCLC migration was also examined in H460 and SPC-A1 cells. A new miR-138 downstream target, cyclin D3 (CCND3), was assessed by dual-luciferase reporter assay and quantitative real-time PCR (qRT-PCR). CCND3 was then ectopically overexpressed in H460 and SPC-A1 cells. The effects of forced overexpression of CCND3 on miR-138-induced NSCLC regulations were further examined by proliferation, cell cycle, cisplatin sensitivity, and migration assays, respectively. Lentivirus-induced miR-138 upregulation inhibited NSCLC proliferation and cell cycle division, in line with previous findings. Moreover, we found that miR-138 upregulation had other anti-tumor effects, such as increasing cisplatin sensitivity and reducing cancer migration, in H460 and SPC-A1 cells. Luciferase assay and qRT-PCR showed that CCND3 was directly targeted by miR-138. Forced overexpression of CCND3 in H460 and SPC-A1 cells reversed the anti-tumor effects of miR-138 upregulation on cancer cell growth, cell cycle, cisplatin sensitivity, and migration. Our study revealed novel anti-cancer effects of miR-138 upregulation in NSCLC, as well as its new molecular target of CCND3.