The RET Fusion Gene and Its Correlation with Demographic and Clinicopathological Features of Non-small Cell Lung Cancer: a Meta-analysis

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2015 May 16

PMID 25975578

Citations 26

Authors

Chen Lin

Shanshan Wang

WeiWei Xie

Jianhua Chang

Yu Gan

Affiliations

Soon will be listed here.

Abstract

Purpose: The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC.

Methods: PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in meta-analysis. Subgroup analysis according to patients' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation.

Results: Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR = 0.55, 95%CI = 0.35-0.85) than male patients and in young (<60) patients (OR = 0.43, 95%CI = 0.19-0.99) than old patients (≤60), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR = 0.28, 95% CI = 0.16-0.49), and in patients with lung adenocarcinomas (OR = 3.59, 95%CI = 1.50-8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed.

Conclusion: RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.

Citing Articles

First-line selpercatinib for a patient with fusion-positive pulmonary large cell neuroendocrine carcinoma.

Eihuku T, Miwa S, Oshima T, Ohba H, Shirai M Respir Med Case Rep. 2024; 52:102116.

PMID: 39350958 PMC: 11440289. DOI: 10.1016/j.rmcr.2024.102116.

Combining demographic data and transvaginal ultrasonography: a predictive model for endometrial carcinoma in postmenopausal patients.

Li X, Wang H, Wang T, Cui H, Wu L, Wang W BMC Womens Health. 2024; 24(1):539.

PMID: 39334255 PMC: 11429476. DOI: 10.1186/s12905-024-03374-8.

Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China.

Lu S, Shen L, Wang Q, Chen H, Zhao Y, Li Y Adv Ther. 2024; 41(11):4248-4265.

PMID: 39316291 DOI: 10.1007/s12325-024-02983-x.

Molecular Landscape and Therapeutic Strategies against Colorectal Cancer.

Patel A, Gulhati P Cancers (Basel). 2024; 16(8).

PMID: 38672633 PMC: 11049251. DOI: 10.3390/cancers16081551.

Lung cancer in patients who have never smoked - an emerging disease.

Lopiccolo J, Gusev A, Christiani D, Janne P Nat Rev Clin Oncol. 2024; 21(2):121-146.

PMID: 38195910 PMC: 11014425. DOI: 10.1038/s41571-023-00844-0.

References

Girard N . Other signalization targets. Target Oncol. 2013; 8(1):69-77. DOI: 10.1007/s11523-012-0246-5. View

Tsuta K, Kohno T, Yoshida A, Shimada Y, Asamura H, Furuta K . RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis. Br J Cancer. 2014; 110(6):1571-8. PMC: 3960615. DOI: 10.1038/bjc.2014.36. View

Takahashi M, Ritz J, Cooper G . Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985; 42(2):581-8. DOI: 10.1016/0092-8674(85)90115-1. View

Cote M, Kardia S, Wenzlaff A, Ruckdeschel J, Schwartz A . Risk of lung cancer among white and black relatives of individuals with early-onset lung cancer. JAMA. 2005; 293(24):3036-42. DOI: 10.1001/jama.293.24.3036. View

Pan Y, Zhang Y, Li Y, Hu H, Wang L, Li H . ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer. 2014; 84(2):121-6. DOI: 10.1016/j.lungcan.2014.02.007. View

Chang A, Parikh P, Thongprasert S, Tan E, Perng R, Ganzon D . Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: subset analysis from the ISEL study. J Thorac Oncol. 2007; 1(8):847-55. View

Wang R, Hu H, Pan Y, Li Y, Ye T, Li C . RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol. 2012; 30(35):4352-9. DOI: 10.1200/JCO.2012.44.1477. View

Pallis A, Syrigos K . Lung cancer in never smokers: disease characteristics and risk factors. Crit Rev Oncol Hematol. 2013; 88(3):494-503. DOI: 10.1016/j.critrevonc.2013.06.011. View

Putzer B, Drosten M . The RET proto-oncogene: a potential target for molecular cancer therapy. Trends Mol Med. 2004; 10(7):351-7. DOI: 10.1016/j.molmed.2004.06.002. View

10.

Yoo S, Jin G, Jung H, Hong M, Choi J, Jeon H . RET fusion genes in Korean non-small cell lung cancer. J Korean Med Sci. 2013; 28(10):1555-8. PMC: 3795183. DOI: 10.3346/jkms.2013.28.10.1555. View

11.

Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T . KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012; 18(3):375-7. PMC: 6430196. DOI: 10.1038/nm.2644. View

12.

Suehara Y, Arcila M, Wang L, Hasanovic A, Ang D, Ito T . Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions. Clin Cancer Res. 2012; 18(24):6599-608. PMC: 4234119. DOI: 10.1158/1078-0432.CCR-12-0838. View

13.

Lee Y, Kim J, Kim S, Ha S, Mok T, Mitsudomi T . Lung cancer in never smokers: change of a mindset in the molecular era. Lung Cancer. 2011; 72(1):9-15. DOI: 10.1016/j.lungcan.2010.12.013. View

14.

Drilon A, Wang L, Hasanovic A, Suehara Y, Lipson D, Stephens P . Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov. 2013; 3(6):630-5. PMC: 4160032. DOI: 10.1158/2159-8290.CD-13-0035. View

15.

Kodama T, Tsukaguchi T, Satoh Y, Yoshida M, Watanabe Y, Kondoh O . Alectinib shows potent antitumor activity against RET-rearranged non-small cell lung cancer. Mol Cancer Ther. 2014; 13(12):2910-8. DOI: 10.1158/1535-7163.MCT-14-0274. View

16.

Couraud S, Zalcman G, Milleron B, Morin F, Souquet P . Lung cancer in never smokers--a review. Eur J Cancer. 2012; 48(9):1299-311. DOI: 10.1016/j.ejca.2012.03.007. View

17.

Pan Q, Wang Y, Chen J, Xu G, Chen B, Pan J . Investigation of the epidermal growth factor receptor mutation rate in non-small cell lung cancer patients and the analysis of associated risk factors using logistic regression. Oncol Lett. 2014; 8(2):813-818. PMC: 4081401. DOI: 10.3892/ol.2014.2160. View

18.

Phay J, Shah M . Targeting RET receptor tyrosine kinase activation in cancer. Clin Cancer Res. 2010; 16(24):5936-41. DOI: 10.1158/1078-0432.CCR-09-0786. View

19.

Dabir S, Babakoohi S, Kluge A, Morrow J, Kresak A, Yang M . RET mutation and expression in small-cell lung cancer. J Thorac Oncol. 2014; 9(9):1316-23. DOI: 10.1097/JTO.0000000000000234. View

20.

Gainor J, Shaw A . Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013; 18(7):865-75. PMC: 3720641. DOI: 10.1634/theoncologist.2013-0095. View