Prognostic Value of TGF-β in Lung Cancer: Systematic Review and Meta-analysis

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2019 Jul 17

PMID 31307405

Citations 44

Authors

Jue Li

Cheng Shen

Xin Wang

Yutian Lai

Kun Zhou

Pengfei Li

Lunxu Liu

Guowei Che

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer is the most important cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not improved. Transforming growth factor beta or TGF-β is a polypeptide member of the transforming growth factor beta superfamily of cytokines, while far fewer clinical studies addressing the association between TGF-β expression and the disease prognosis have been reported up to now. Therefore, our meta-analysis aims to determine the prognostic significance of TGF-β expression in lung cancer patients.

Methods: PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literature citations. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I statistic were used to estimate the level of heterogeneity. The publication bias was detected by Begg's test and Egger's test.

Results: Eight eligible studies involving 579 patients were selected for this meta-analysis. The combined HR for the eight eligible studies was 2.17 (95% CI: 1.71-2.77, P < 0.00001) and heterogeneity of overall prognosis was relatively low (I = 14.2%, P = 0.319). We further undertook the subgroup analysis including assessment of the association between TGF-β expression and pathology of the lung cancer, treatment and quantity of sample in studies. All the results revealed that a significantly high TGF-β expression in patients was an indicator of poor survival. Neither Begg's test nor Egger's test found publication bias in any analysis.

Conclusions: The present evidence indicates that TGF-β expression can significantly predict the worse prognosis in patients with lung cancer. The findings of our meta-analysis may be confirmed in the future by the use of more updated review pooling and additional relevant investigations.

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References

Hasegawa Y, Takanashi S, Kanehira Y, Tsushima T, Imai T, Okumura K . Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer. 2001; 91(5):964-71. View

Zhao L, Ji W, Zhang L, Ou G, Feng Q, Zhou Z . Changes of circulating transforming growth factor-beta1 level during radiation therapy are correlated with the prognosis of locally advanced non-small cell lung cancer. J Thorac Oncol. 2010; 5(4):521-5. DOI: 10.1097/JTO.0b013e3181cbf761. View

Kumar S, Guleria R, Mohan A, Singh V, Ali A, Bharti A . Utility of plasma tumour necrosis factor-alpha and transforming growth factor-beta1 as predictors of survival and treatment outcome in advanced non-small cell lung carcinoma. Biomarkers. 2010; 15(5):446-53. DOI: 10.3109/1354750X.2010.485699. View

Kumar S, Guleria R, Mohan A, Singh V, Bharti A, Das B . Efficacy of plasma TGF-β1 level in predicting therapeutic efficacy and prognosis in patients with advanced non-small cell lung cancer. Cancer Invest. 2011; 29(3):202-7. DOI: 10.3109/07357907.2010.543208. View

Vazquez P, Carlini M, Daroqui M, Colombo L, Dalurzo M, Smith D . TGF-beta specifically enhances the metastatic attributes of murine lung adenocarcinoma: implications for human non-small cell lung cancer. Clin Exp Metastasis. 2013; 30(8):993-1007. DOI: 10.1007/s10585-013-9598-1. View

Gao Y, Wang Y, Sun L, Meng Q, Cai L, Dong X . Expression of TGFβ-1 and EHD1 correlated with survival of non-small cell lung cancer. Tumour Biol. 2014; 35(9):9371-80. DOI: 10.1007/s13277-014-2164-x. View

Huang A, Liu S, Qi W, Zhao Y, Li Y, Lei B . TGF-β1 protein expression in non-small cell lung cancers is correlated with prognosis. Asian Pac J Cancer Prev. 2014; 15(19):8143-7. DOI: 10.7314/apjcp.2014.15.19.8143. View

Liu S, Yuan S, Wu H, Liu J, Huang C . The Clinical Research of Serum VEGF, TGF-β1, and Endostatin in Non-small Cell Lung Cancer. Cell Biochem Biophys. 2014; 72(1):165-9. DOI: 10.1007/s12013-014-0431-5. View

Yang H, Zhan L, Yang T, Wang L, Li C, Zhao J . Ski prevents TGF-β-induced EMT and cell invasion by repressing SMAD-dependent signaling in non-small cell lung cancer. Oncol Rep. 2015; 34(1):87-94. DOI: 10.3892/or.2015.3961. View

10.

Ye Y, Liu S, Wu C, Sun Z . TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis. J Mol Histol. 2015; 46(4-5):365-75. DOI: 10.1007/s10735-015-9633-4. View

11.

Okayama A, Miyagi Y, Oshita F, Ito H, Nakayama H, Nishi M . Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial-Mesenchymal Transition Induced with TGF-β. J Proteome Res. 2015; 14(10):4127-36. DOI: 10.1021/acs.jproteome.5b00082. View

12.

Xie M, He C, Wei S . [Relationship between Expression of TGF-β1, Smad2, Smad4 and Prognosis  of Patients with Resected Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2015; 18(9):543-8. PMC: 6000115. DOI: 10.3779/j.issn.1009-3419.2015.09.03. View

13.

Elmansuri A, Tanino M, Mahabir R, Wang L, Kimura T, Nishihara H . Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer. Oncotarget. 2016; 7(19):27094-107. PMC: 5053635. DOI: 10.18632/oncotarget.8314. View

14.

Yang L, Zhang F, Wang X, Tsai Y, Chuang K, Keng P . A FASN-TGF-β1-FASN regulatory loop contributes to high EMT/metastatic potential of cisplatin-resistant non-small cell lung cancer. Oncotarget. 2016; 7(34):55543-55554. PMC: 5342435. DOI: 10.18632/oncotarget.10837. View

15.

Peng L, Yuan X, Zhang C, Ye F, Zhou H, Li W . High TGF-β1 expression predicts poor disease prognosis in hepatocellular carcinoma patients. Oncotarget. 2017; 8(21):34387-34397. PMC: 5470976. DOI: 10.18632/oncotarget.16166. View

16.

Khan G, Gao Y, Gu M, Wang L, Khan S, Naeem F . TGF-β1 Causes EMT by Regulating N-Acetyl Glucosaminyl Transferases via Downregulation of Non Muscle Myosin II-A through JNK/P38/PI3K Pathway in Lung Cancer. Curr Cancer Drug Targets. 2017; 18(2):209-219. DOI: 10.2174/1568009617666170807120304. View

17.

Xu Y, Lou Z, Lee S . Arctigenin represses TGF-β-induced epithelial mesenchymal transition in human lung cancer cells. Biochem Biophys Res Commun. 2017; 493(2):934-939. DOI: 10.1016/j.bbrc.2017.09.117. View

18.

Wei Y, Li D, Wang D, Qiu T, Liu K . WITHDRAWN: Evaluation of microRNA-203 in bone metastasis of patients with non-small cell lung cancer through TGF-β/SMAD2 expression. Oncol Rep. 2017; . DOI: 10.3892/or.2017.5987. View

19.

Xiong Y, Zhang J, Shi L, Ning Y, Zhu Y, Chen S . NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation. Oncotarget. 2017; 8(41):71024-71037. PMC: 5642615. DOI: 10.18632/oncotarget.20297. View

20.

Wang H, Wu Q, Zhang Y, Zhang H, Wang Y, Wang W . TGF-β1-induced epithelial-mesenchymal transition in lung cancer cells involves upregulation of miR-9 and downregulation of its target, E-cadherin. Cell Mol Biol Lett. 2017; 22:22. PMC: 5668967. DOI: 10.1186/s11658-017-0053-1. View