Elsevier

Lung Cancer

Volume 87, Issue 1, January 2015, Pages 1-7
Lung Cancer

FGFR1 amplification in lung squamous cell carcinoma: A systematic review with meta-analysis

https://doi.org/10.1016/j.lungcan.2014.11.009Get rights and content

Highlights

  • FGFR1 amplification is about 19% in lung squamous cell carcinoma patients.

  • Gender, stage, differentiation, ethnicities and test methods have no influence on FGFR1 amplification.

  • FGFR1 amplification trends to correlate with lymph node metastasis and smoking.

  • Whether FGFR1 amplification has the effect on survival remains controversial.

Abstract

Introduction

Current targeted therapy proves no effective outcomes in lung squamous cell carcinoma (SQCC). Recent studies suggested that FGFR1 would be promising. This systematic review elaborated FGFR1 amplification in lung SQCC.

Methods

An electronic search was conducted on PubMed, EMBASE, Web of SCI, Google Scholar and Cochrane Library. Eligible studies regarding incidence of FGFR1 amplification in lung SQCC and correlation between FGFR1 amplification and clinicopathological features or survival were extracted and analyzed.

Results

We identified 13 eligible studies with a total of 1798 patients. The results showed about 19% of FGFR1 amplification (95% CI: 0.15–0.24; I2 = 84.5%; p = 0.000). Using the same test method: FISH, definition and ethnicity, the rates were 17% (95% CI: 0.14–0.20; I2 = 53.1%; p = 0.037), 21% (95% CI: 0.18–0.24; I2 = 0; p = 0.615), and 16% (95% CI: 0.13–0.19; I2 = 72.1%; p = 0.028), respectively. Pearson's correlation analysis suggested that smoking status was highly correlated with FGFR1 amplification (coefficient = 0.961, p < 0.001). FGFR1 amplification was significantly correlated with lymph node metastasis (OR: 2.27; 95% CI: 1.62–3.20; p = 0.000), but not correlated with gender (OR: 1.12; 95% CI: 0.90–1.38; p = 0.91), differentiation (OR: 1.02; 95% CI: 0.76–1.38; p = 0.959) and stage (OR: 0.93; 95% CI: 0.73–1.19; p = 0.877) in lung SQCC patients. With respect to survival, FGFR1 amplification had no influence on PFS (HR: 1.57; 95% CI: 0.85–2.30; p = 0.259) and OS (HR: 1.40; 95% CI: 0.90–1.89; p = 0.416) for SQCC patients.

Conclusion

FGFR1 amplification is about 19%. Gender, stage, differentiation, ethnicities and test methods have no influence on FGFR1 amplification. FGFR1 amplification trends to correlate with lymph node metastasis and smoking. Whether FGFR1 amplification has effect on survival remains controversial.

Introduction

Although there are some improvements in diagnosis and therapy of lung cancer, it is still the leading cause of cancer-related mortality worldwide resulting in more than 1 million deaths annually [1]. The discovery of mutations in the epidermal growth factor receptor (EGFR) kinase, as well as fusions involving anaplastic lymphoma kinase (ALK), has led to a marked change in the treatment of patients with lung adenocarcinoma [2], [3], [4]. Unfortunately, these oncogenic drivers are not typically presented in the second most common type of lung cancer, lung squamous cell carcinoma (SQCC). That is to way, EGFR or ALK inhibitors are ineffective in lung SQCC. Hence we need to seek for other significant markers, which can be new targets for SQCC therapy.

To date, some studies have already identified regions of somatic copy number alterations in lung SQCC, including amplification of SOX2, PDGFRA and fibroblast growth factor receptor 1 (FGFR1), discoidin domain receptor 2 (DDR2) mutation, and phosphatidylinositol 3-kinase catalytic alpha (PI3KCA) amplification. DNA sequencing studies of lung SQCC have reported recurrent mutations in several genes, including TP53, NFE2L2, KEAP1, BAI3, FBXW7, GRM8, MUC16, RUNX1T1, STK11 and ERBB4 [5], [6], [7], [8]. Recent processes in molecular biology have confirmed that FGFR1 and its amplification were common in SQCC [5], [9].

The FGFR tyrosine kinase family comprises four kinases: FGFR1, FGFR2, FGFR3, and FGFR4 [10], [11]. They play an essential role in the cancer development and differentiation [6], [10]. In vitro and in vivo studies have shown that FGFR1-mediated signaling pathway played a pivotal role in NSCLC cell growth, survival and migration. Moreover, FGFR1 specific small molecule inhibitors have a selective growth inhibitory effect on FGFR1 amplified tumors [6], [9], [12]. Amplification or activation of FGFR1 has been reported in orals squamous carcinoma, esophageal squamous cell carcinomas, ovarian cancer, bladder cancer and lung cancer [13], [14], [15], [16], [17], [18], which is a promising and novel therapeutic target in these tumors.

Although FGFR1 amplification in SQCC has been investigated for several years, the accurate rate of amplification in lung SQCC, the influence of FGFR1 amplification rate and the effect on survival, still remain unclear. Considering different results of published studies, we performed this meta-analysis to determine the FGFR1 amplification in lung SQCC.

Section snippets

Search strategy

A thorough electronic search of the main computerized databases of interest was conducted, including PubMed, EMBASE, Web of SCI, and Google Scholar using the terms“FGRF1”, “FGFR1 amplification”, and “lung cancer”. An upper date limit of May 31, 2014 was applied; no lower date limit was used. The Cochrane Library was also reviewed for relevant articles. All references of relevant articles were scanned and all additional studies of potential interest were retrieved for further analysis. Two

Selection of studies

A total of 76 potentially relevant studies were identified in the literature search (Fig. 1). Nine were found to be duplicates and were excluded. Another 40 were excluded on the basis of titles or abstracts, including 13 animal experiments, 9 reviews, 8 meeting abstracts and 10 not relevant. Fourteen studies were excluded after full text assessment for eligibility. A total of 13 studies [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31] met the eligibility criteria and

Discussion

To our knowledge, this is the first systematic review to elaborate more details about the FGFR1 amplification in lung SQCC. Our review included a total of 13 studies that involved 1798 lung SQCC patients. All of included articles have the definition of FGFR1 amplification but not all are accurate. As the reported rate of FGFR1 amplification, there is significant heterogeneity in all included articles in the meta-analysis. Hence we performed subgroup analysis. The results of subgroup analysis

Conflict of interest statement

None declared.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81172101) and the key project of the Science and Technology Commission of Shanghai Municipality (No. 11JC1411301).

Acknowledgments

Tao Jiang and Caicun Zhou designed the study; Tao Jiang, Guanghui Gao and Guoxin Fan independently reviewed the included literatures; Tao Jiang drafted the manuscript; Guoxin Fan and Mu Li gave critical comments and revised the paper; Caicun Zhou approved the final version of the manuscript.

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