Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Systematic Review Article

Prognostic Impact of Tissue Inhibitor of Metalloproteinase-1 in Non- Small Cell Lung Cancer: Systematic Review and Meta-Analysis

Author(s): Gurudeeban Selvaraj, Satyavani Kaliamurthi, Shuhuang Lin, Keren Gu and Dong-Qing Wei*

Volume 26, Issue 42, 2019

Page: [7694 - 7713] Pages: 20

DOI: 10.2174/0929867325666180904114455

Price: $65


Background and Objectives: Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is a multifunctional natural matrixin inhibitor that is generally considered a negative regulator of cancer metastasis. Clinical studies reporting the prognostic value of TIMP-1 in Non-small Cell Lung Cancer (NSCLC) are inconsistent. Therefore, the present study aimed to determine the prognostic impact of TIMP-1 expression in NSCLC.

Methods: Appropriate studies with full-text articles were identified in searches of the China National Knowledge Infrastructure (CNKI), Cochrane Library, PubMed, and Web of Science databases up to March 7, 2018. The pooled Hazard Ratio (HR) of overall survival with a 95% confidence interval (95% CI) was employed to assess the relationship between the expression of TIMP-1 and NSCLC patient survival.

Results: The meta-analysis comprised 40 studies including 3,194 patients. Study outcomes indicated that high TIMP-1 expression is independently associated with poor overall survival (HR: 1.60; 95% CI: 1.50, 1.69; P < 0.00001) with 61% of heterogeneity. In addition, we analyzed subgroups, including ethnicities, histological types, percentage of TIMP-1 expression levels, specimens, and tumor stage. All results were statistically significant. The outcome of our meta-analysis indicates that high expression levels of TIMP-1 are correlated with poor prognosis in patients with NSCLC.

Conclusion: Expression levels of TIMP-1 represent a potential prognostic biomarker in NSCLC patients in addition to being a possible therapeutic target.

Keywords: Antiapoptosis, cell proliferation, IHC, meta-analysis, non-small cell lung cancer, tumor invasion, tissue inhibitor of metalloproteinase-1.

Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30.
[] [PMID: 28055103]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[] [PMID: 26808342]
Petersen, I.; Warth, A. Lung cancer: developments, concepts, and specific aspects of the new WHO classification. J. Cancer Res. Clin. Oncol., 2016, 142(5), 895-904.
[] [PMID: 26197868]
Zhang, H.; Guttikonda, S.; Roberts, L.; Uziel, T.; Semizarov, D.; Elmore, S.W.; Leverson, J.D.; Lam, L.T. Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines. Oncogene, 2011, 30(16), 1963-1968.
[] [PMID: 21132008]
Spurr, N.K.; Goodfellow, P.N.; Docherty, A.J. Chromosomal assignment of the gene encoding the human tissue inhibitor of metalloproteinases to Xp11.1-p11.4. Ann. Hum. Genet., 1987, 51(3), 189-194.
[] [PMID: 3688834]
Shen, W.; Zhu, J.; Yu, Z.; Xue, Q. [TIMP-1 secreted by fibroblasts inhibits tumor cell invasion and metastasis in mouse melanoma] Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2009, 26(3), 610-614.
[PMID: 19634683]
Bourboulia, D.; Stetler-Stevenson, W.G. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion. Semin. Cancer Biol., 2010, 20(3), 161-168.
[] [PMID: 20470890]
Brew, K.; Nagase, H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim. Biophys. Acta, 2010, 1803(1), 55-71.
[] [PMID: 20080133]
Wang, N.; Zhu, M.; Tsao, S.W.; Man, K.; Zhang, Z.; Feng, Y. Up-regulation of TIMP-1 by genipin inhibits MMP-2 activities and suppresses the metastatic potential of human hepatocellular carcinoma. PLoS One, 2012, 7(9) e46318
[] [PMID: 23029478]
Jee, B.K.; Park, K.M.; Surendran, S.; Lee, W.K.; Han, C.W.; Kim, Y.S.; Lim, Y. KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochem. Biophys. Res. Commun., 2006, 342(2), 655-661.
[] [PMID: 16488391]
Würtz, S.O.; Schrohl, A.S.; Sørensen, N.M.; Lademann, U.; Christensen, I.J.; Mouridsen, H.; Brünner, N. Tissue inhibitor of metalloproteinases-1 in breast cancer. Endocr. Relat. Cancer, 2005, 12(2), 215-227.
[] [PMID: 15947098]
Chirco, R.; Liu, X.W.; Jung, K.K.; Kim, H.R. Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev., 2006, 25(1), 99-113.
[] [PMID: 16680576]
Kopitz, C.; Gerg, M.; Bandapalli, O.R.; Ister, D.; Pennington, C.J.; Hauser, S.; Flechsig, C.; Krell, H.W.; Antolovic, D.; Brew, K.; Nagase, H.; Stangl, M.; von Weyhern, C.W.; Brücher, B.L.D.M.; Brand, K.; Coussens, L.M.; Edwards, D.R.; Krüger, A. Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res., 2007, 67(18), 8615-8623.
[] [PMID: 17875701]
Ivaska, J.; Pallari, H.M.; Nevo, J.; Eriksson, J.E. Novel functions of vimentin in cell adhesion, migration, and signaling. Exp. Cell Res., 2007, 313(10), 2050-2062.
[] [PMID: 17512929]
Kim, E.S.; Jeong, C.S.; Moon, A. Genipin, a constituent of Gardenia jasminoides Ellis, induces apoptosis and inhibits invasion in MDA-MB-231 breast cancer cells. Oncol. Rep., 2012, 27(2), 567-572.
[] [PMID: 22020372]
Cheng, G.; Fan, X.; Hao, M.; Wang, J.; Zhou, X.; Sun, X. Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer. Mol. Cancer, 2016, 15(1), 30.
[] [PMID: 27130446]
Nalluri, S.; Ghoshal-Gupta, S.; Kutiyanawalla, A.; Gayatri, S.; Lee, B.R.; Jiwani, S.; Rojiani, A.M.; Rojiani, M.V. TIMP-1 inhibits apoptosis in lung adenocarcinoma cells via interaction with Bcl-2. PLoS One, 2015, 10(9)e0137673
[] [PMID: 26366732]
Lee, S.J.; Yoo, H.J.; Bae, Y.S.; Kim, H.J.; Lee, S.T. TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive G protein and c-Src. Biochem. Biophys. Res. Commun., 2003, 312(4), 1196-1201.
[] [PMID: 14652000]
Lai, C-Y.; Chang, W-S.; Hsieh, Y-H.; Hsu, C-M.; Tsai, C-W.; Chen, A-C.; Wang, C-H.; Bau, D-T. Association of tissue inhibitor of metalloproteinase-1 genotypes with lung cancer risk in taiwan. Anticancer Res., 2016, 36(1), 155-160.
[PMID: 26722039]
Michael, M.; Babic, B.; Khokha, R.; Tsao, M.; Ho, J.; Pintilie, M.; Leco, K.; Chamberlain, D.; Shepherd, F.A. Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer. J. Clin. Oncol., 1999, 17(6), 1802-1808.
[] [PMID: 10561218]
Liang, J.; Lin, M.; Xie, M.; Liu, X. [Expressions of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 and their correlation with metastasis and prognosis in lung cancer] Zhongguo Fei Ai Za Zhi, 2003, 6(1), 46-50.
[] [PMID: 21262148]
Suemitsu, R.; Yoshino, I.; Tomiyasu, M.; Fukuyama, S.; Okamoto, T.; Maehara, Y. Serum tissue inhibitors of metalloproteinase-1 and -2 in patients with non-small cell lung cancer. Surg. Today, 2004, 34(11), 896-901.
[] [PMID: 15526122]
Zhu, Z.H.; Sun, B.Y.; Ma, Y.; Shao, J.Y.; Long, H.; Zhang, X.; Fu, J.H.; Zhang, L.J.; Su, X.D.; Wu, Q.L.; Ling, P.; Chen, M.; Xie, Z.M.; Hu, Y.; Rong, T.H. Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer. J. Clin. Oncol., 2009, 27(7), 1091-1099.
[] [PMID: 19188679]
Pesta, M.; Kulda, V.; Kucera, R.; Pesek, M.; Vrzalova, J.; Liska, V.; Pecen, L.; Treska, V.; Safranek, J.; Prazakova, M.; Vycital, O.; Bruha, J.; Holubec, L.; Topolcan, O. Prognostic significance of TIMP-1 in non-small cell lung cancer. Anticancer Res., 2011, 31(11), 4031-4038.
[PMID: 22110238]
Gumustekin, M.; Kargi, A.; Bulut, G.; Gozukizil, A.; Ulukus, C.; Oztop, I.; Atabey, N. HGF/c-Met overexpressions, but not met mutation, correlates with progression of non-small cell lung cancer. Pathol. Oncol. Res., 2012, 18(2), 209-218.
[] [PMID: 21779788]
Moher, D.; Shamseer, L.; Clarke, M.; Ghersi, D.; Liberati, A.; Petticrew, M.; Shekelle, P.; Stewart, L.A. PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev., 2015, 4(1), 1.
[] [PMID: 25554246]
Wells, G.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in metaanalyses. 2013, Available at: (Accessed Date: November 02, 2017)
Higgins, J.P.T.; Green, S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Updated March 2011]. The Cochrane Collaboration, 2011. Available from:
Zein, H. Tran, V.; Abdelmotaleb Ghazy, A.; Mohammed, A.T.; Ahmed, A.; Iraqi, A.; Nguyen, H. How to extract data from graphs using plot digitizer or getdata graph digitizer. Tech. Rep., 2015, pp. 1-13.
Aljada, I.S.; Ramnath, N.; Donohue, K.; Harvey, S.; Brooks, J.J.; Wiseman, S.M.; Khoury, T.; Loewen, G.; Slocum, H.K.; Anderson, T.M.; Bepler, G.; Tan, D. Upregulation of the tissue inhibitor of metalloproteinase-1 protein is associated with progression of human non-small-cell lung cancer. J. Clin. Oncol., 2004, 22(16), 3218-3229.
[] [PMID: 15249585]
An, H.J.; Lee, Y-J.; Hong, S.A.; Kim, J-O.; Lee, K.Y.; Kim, Y.K.; Park, J.K.; Kang, J-H. The prognostic role of tissue and serum MMP-1 and TIMP-1 expression in patients with non-small cell lung cancer. Pathol. Res. Pract., 2016, 212(5), 357-364.
[ 10.1016/j.prp.2015.11.014] [PMID: 26995105]
Blumenschein, G.R., Jr; Reck, M.; Fossella, F.; Stewart, D.J.; Lathia, C.; Peña, C. Plasma biomarkers correlating with clinical outcome in a phase II study of sorafenib in advanced NSCLC. Cancer Biomark., 2011-2012, 10(6), 287-298.
[] [PMID: 22820084]
Gouyer, V.; Conti, M.; Devos, P.; Zerimech, F.; Copin, M.C.; Créme, E.; Wurtz, A.; Porte, H.; Huet, G. Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent. Cancer, 2005, 103(8), 1676-1684.
[] [PMID: 15754326]
Hoikkala, S.; Pääkkö, P.; Soini, Y.; Mäkitaro, R.; Kinnula, V.; Turpeenniemi-Hujanen, T. Tissue MMP-2 and MMP-9 [corrected] are better prognostic factors than serum MMP-2/TIMP-2--complex or TIMP-1 [corrected] in stage [corrected] I-III lung carcinoma. Cancer Lett., 2006, 236(1), 125-132.
[] [PMID: 15982804]
Iniesta, P.; Morán, A.; De Juan, C.; Gómez, A.; Hernando, F.; García-Aranda, C.; Frías, C.; Díaz-López, A.; Rodríguez-Jiménez, F.J.; Balibrea, J.L.; Benito, M. Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer. Oncol. Rep., 2007, 17(1), 217-223.
[] [PMID: 17143501]
Lou, E.; Johnson, M.; Sima, C.; Gonzalez-Espinoza, R.; Fleisher, M.; Kris, M.G.; Azzoli, C.G. Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer. Cancer Biomark., 2014, 14(4), 207-214.
[] [PMID: 24934363]
Simi, L.; Andreani, M.; Davini, F.; Janni, A.; Pazzagli, M.; Serio, M.; Orlando, C. Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR. Lung Cancer, 2004, 45(2), 171-179.
[] [PMID: 15246188]
Ylisirniö, S.; Höyhtyä, M.; Mäkitaro, R.; Pääakkö, P.; Risteli, J.; Kinnula, V.L.; Turpeenniemi-Hujanen, T.; Jukkola, A. Elevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer. Clin. Cancer Res., 2001, 7(6), 1633-1637.
[PMID: 11410500]
Cao, J.W.; Liud, S.; Panh, H. Expressions of MMP-9 and TIMP-1 in non-small cell lung cancer and the relations to Metastasis and prognosis. Chin. J. Oncol. Prev. Treat., 2010, 2(3), 179-182.
Chen, G.Q.; Gu, Y.; Liu, F. The expression and signif-icance of immunohistochemical indexesin the prognosis of non-small cell lung cancer patients. China Trop. Med., 2006, 6(10), 1755-1757.
Fong, K.M.; Kida, Y.; Zimmerman, P.V.; Smith, P.J. TIMP1 and adverse prognosis in non-small cell lung cancer. Clin. Cancer Res., 1996, 2(8), 1369-1372.
[PMID: 9816309]
Han, Q.; Kong, N.; Wu, G. Expression and clinical signifi-cance of vascular endothelial growth factor, matrix metallo-proteinase-9 and tissue inhibitor of metalloproteinase in non-small cell lung cancer. China Med. Frontier J., 2015, 7(5), 109-111.
He, B.; Li, L.; Wu, D. Expression of MMP-9 and TIMP-1 in non-small cell lung carcinoma. Shaanxi Med. J., 2007, 36(9), 1232-1235.
Jiang, X.; Meng, Q.; Chen, D.; Fan, H.; Gu, Li. Expression of MMP-9 and TIMP-1 in non-small cell lung cancer and their clinical value. Med. J. Chin. People' s Armed Police Forces., 2002, 13(02), 67.
Kim, R.H.; Yang, S.H.; Jeong, E.T. The relationship between expression of matrix metalloproteinase (MMPs)-2,9 and Tis-sue inhibitors of metalloproteinase (TIMPs) - 1, 2 and sur-vival time in resected non-small cell lung cancer. Tuberc. Respir. Dis. (Seoul), 2002, 52(5), 453-462.
Kumaki, F.; Matsui, K.; Kawai, T.; Ozeki, Y.; Yu, Z.X.; Ferrans, V.J.; Travis, W.D. Expression of matrix metalloproteinases in invasive pulmonary adenocarcinoma with bronchioloalveolar component and atypical adenomatous hyperplasia. Am. J. Pathol., 2001, 159(6), 2125-2135.
[] [PMID: 11733363]
Li, Q.; Wang, Y.; Xie, C.; Qiu, X.; Wang, E. Expression of MMP-2, MMP-9, TIMP-1 in non-small cell lung cancer and its relationship with prognosis. Chin. J. Lung Cancer., 2004, 7(6), 497-500.
[PMID: 21251406]
Li, J.; Liu, A.; Chen, B. Expression and clinical significance of S100A 4, MMP 9 and TIMP 1 in non-small cell lung cancer. Shaanxi Med. J., 2007, 9(36), 1149-1152.
Liang, N.; Wan, X. Correlation between expression of MMP-9, TIMP-1 and VEGF and the invasion of non small cell lung cancer. J. Kunming Med. Univ., 2016, 37(10), 67-70.
Lim, B.J.; Jung, S.S.; Choi, S.Y.; Lee, C.S. Expression of metastasis-associated molecules in non-small cell lung cancer and their prognostic significance. Mol. Med. Rep., 2010, 3(1), 43-49.
[ 10.3892/mmr_00000216] [PMID: 21472198]
Nawrocki, B.; Polette, M.; Marchand, V.; Monteau, M.; Gillery, P.; Tournier, J.M.; Birembaut, P. Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses. Int. J. Cancer, 1997, 72(4), 556-564.
[<556:AID-IJC2>3.0.CO;2-P] [PMID: 9259391]
Nie, C.; Xie, H.; Ke, H.; Zhou, Z. The relationship between TIMP-1 and MMP-9 and the prognosis of patients with non-small cell lung cancer. J. Clin. Med., 2017, 4(89), 17438-17439.
Rui, J.; Cuihuan, W.; Shiying, Y. Expression of MMP-13 And TIMP-1 and their correlation with prognosis in nonsmall cell lung cancer. Chinese J. Histochem. Cytochem, 2008, 2, 00.
Tang, C.; Luo, D.; Yang, H.; Wang, Q.; Zhang, R.; Liu, G.; Zhou, X. Expression of SHP2 and related markers in non-small cell lung cancer: a tissue microarray study of 80 cases. Appl. Immunohistochem. Mol. Morphol., 2013, 21(5), 386-394.
[] [PMID: 23343958]
Thomas, P.; Khokha, R.; Shepherd, F.A.; Feld, R.; Tsao, M.S. Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer. J. Pathol., 2000, 190(2), 150-156.
[<150:AID-PATH510>3.0.CO;2-W] [PMID: 10657012]
Wang, W.; Chen, S.; Wen, J.; Xiao, G.; Zhou, S. Expression and metastasis prognosis of CD44V6 MMP2, MMP9, TIMP1 and TIMP2 in non- small cell lung cancer. China Med. Engg., 2007, 15(2), 122-130.
Wills, B.; Cardona, A.F.; Rojas, L.; Ruiz-Patiño, A.; Arrieta, O.; Reguart, N.; Carranza, H.; Vargas, C.; Otero, J.; Corrales, L.; Martín, C.; Cuello, M.; Pino, L.E.; Rolfo, C.; Rosell, R.; Zatarain-Barrón, Z.L. Latin-american consortium for the investigation of lung cancer (CLICaP). Survival outcomes according to TIMP1 and EGFR expression in heavily treated patients with advanced non-small cell lung cancer who received biweekly irinotecan plus bevacizumab. Anticancer Res., 2017, 37(11), 6429-6436.
[PMID: 29061829]
Xu, H.; Chen, X.; Huang, D.; Huang, X.; Wang, D.; Huo, Q. Expression and significance of MMP-9 and TIMP-1 in Non-small cell lung cancer. J. Clin. Exp. Pathol., 2011, 27(10), 1084-1086.
Yang, B.; Sheng, H.; Yuan, C. Expression of MMP-9 and its inhibitor TIMP-1 in non-small cell lung cancer and its correlation with pathological features. Chin J. Lab. Diagn., 2009, 13(9), 1166-1167.
Zhou, J.; Wang, W.; Wen, J. Clinicopathological significance of MMP2, MMP9, TIMP1 and TIMP2 expressions in human non-small cell lung cancer. Pract. Prev. Med., 2006, 13(1), 23-26.
Zhu, B.; Zhao, H.; Wang, Y.; Lao, M.; Huang, Z.; Liu, Z.; Xie, J.; Ou, C. Research on the expressions of KAI1 gene, TIMP-1 and MMP-9 and their correlations with clinico-pathologic features of non-small cell lung cancer. Lab. Med., 2014, 29(3), 279-282.
Higgins, J.P.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med., 2002, 21(11), 1539-1558.
[] [PMID: 12111919]
Egger, M.; Davey Smith, G.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109), 629-634.
[] [PMID: 9310563]
Duval, S.; Tweedie, R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 2000, 56(2), 455-463.
[] [PMID: 10877304]
Zhong, A. Expression of MMP-2 and TIMP-1 and the corre-lation with clinical stages and metastasis in lung carcinoma patients. J. North China Coal Med. College, 2007, 9(5), 305-307.
Jiang, Y.; Goldberg, I.D.; Shi, Y.E. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene, 2002, 21(14), 2245-2252.
[] [PMID: 11948407]
Lempinen, M.; Lyytinen, I.; Nordin, A.; Tervahartiala, T.; Mäkisalo, H.; Sorsa, T.; Isoniemi, H. Prognostic value of serum MMP-8, -9 and TIMP-1 in patients with hepatocellular carcinoma. Ann. Med., 2013, 45(7), 482-487.
[] [PMID: 23962148]
Tsagaraki, I.; Tsilibary, E.C.; Tzinia, A.K. TIMP-1 interaction with αvβ3 integrin confers resistance to human osteosarcoma cell line MG-63 against TNF-α-induced apoptosis. Cell Tissue Res., 2010, 342(1), 87-96.
[] [PMID: 20798956]
Roy, R.; Zurakowski, D.; Wischhusen, J.; Frauenhoffer, C.; Hooshmand, S.; Kulke, M.; Moses, M.A. Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies. Br. J. Cancer, 2014, 111(9), 1772-1779.
[] [PMID: 25137018]
Bodnar, M.; Szylberg, Ł.; Kazmierczak, W.; Marszalek, A. Tumor progression driven by pathways activating matrix metalloproteinases and their inhibitors. J. Oral Pathol. Med., 2015, 44(6), 437-443.
[] [PMID: 25244188]
Cui, H.; Seubert, B.; Stahl, E.; Dietz, H.; Reuning, U.; Moreno-Leon, L.; Ilie, M.; Hofman, P.; Nagase, H.; Mari, B.; Krüger, A. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene, 2015, 34(28), 3640-3650.
[] [PMID: 25263437]
Song, T.; Dou, C.; Jia, Y.; Tu, K.; Zheng, X. TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma. Oncotarget, 2015, 6(14), 12061-12079.
[] [PMID: 25909286]
Ikenaka, Y.; Yoshiji, H.; Kuriyama, S.; Yoshii, J.; Noguchi, R.; Tsujinoue, H.; Yanase, K.; Namisaki, T.; Imazu, H.; Masaki, T.; Fukui, H. Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model. Int. J. Cancer, 2003, 105(3), 340-346.
[] [PMID: 12704667]
Liao, C.; Yu, Z.; Guo, W.; Liu, Q.; Wu, Y.; Li, Y.; Bai, L. Prognostic value of circulating inflammatory factors in non-small cell lung cancer: a systematic review and meta-analysis. Cancer Biomark., 2014, 14(6), 469-481.
[] [PMID: 25335739]
Zheng, C.L.; Qiu, C.; Shen, M.X.; Qu, X.; Zhang, T.H.; Zhang, J.H.; Du, J.J. Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis. Asian Pac. J. Cancer Prev., 2015, 16(5), 1881-1895.
[] [PMID: 25773840]
Gong, L.; Wu, D.; Zou, J.; Chen, J.; Chen, L.; Chen, Y.; Ni, C.; Yuan, H. Prognostic impact of serum and tissue MMP-9 in non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget, 2016, 7(14), 18458-18468.
[] [PMID: 26918342]
Wang, X.F.; Zhu, Y.T.; Wang, J.J.; Zeng, D.X.; Mu, C.Y.; Chen, Y.B.; Lei, W.; Zhu, Y.H.; Huang, J.A. The prognostic value of interleukin-17 in lung cancer: A systematic review with meta-analysis based on Chinese patients. PLoS One, 2017, 12(9)e0185168
[] [PMID: 28934305]
Alevizakos, M.; Kaltsas, S.; Syrigos, K.N. The VEGF pathway in lung cancer. Cancer Chemother. Pharmacol., 2013, 72(6), 1169-1181.
[] [PMID: 24085262]
Guo, Y.; Xu, F.; Lu, T.; Duan, Z.; Zhang, Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat. Rev., 2012, 38(7), 904-910.
[] [PMID: 22651903]
Pan, B.; Shen, J.; Cao, J.; Zhou, Y.; Shang, L.; Jin, S.; Cao, S.; Che, D.; Liu, F.; Yu, Y. Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer. Sci. Rep., 2015, 5, 16053.
[] [PMID: 26524953]
Jung, K.K.; Liu, X.W.; Chirco, R.; Fridman, R.; Kim, H.R. Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J., 2006, 25(17), 3934-3942.
[] [PMID: 16917503]
Toricelli, M.; Melo, F.H.; Peres, G.B.; Silva, D.C.; Jasiulionis, M.G. Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation. Mol. Cancer, 2013, 12, 22.
[] [PMID: 23522389]
Tierney, J.F.; Stewart, L.A.; Ghersi, D.; Burdett, S.; Sydes, M.R. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8, 16.
[] [PMID: 17555582]
Langfort, R. The new recommendation of the seventh edition of TNM classification for Lung Cancer in pathologic as-sesssment (pTNM).Adv. Respir. Med; , 2010, 78, pp. (6)379-383.
[PMID: 21077028]
Langfort, R. The new recommendation of the 7th edition of TNM classification for Lung Cancer in pathologic assesssment (pTNM).Adv. Respir. Med; , 2010, 78, pp. (6)379-383.
[PMID: 21077028]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy