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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Metastasis | Research article

High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer

Authors: Zaiping Chen, Guiyang Wu, Fubo Ye, Guoping Chen, Qinghao Fan, Hao Dong, Xiongwen Zhu, Chongshan Wu

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Matrix metalloproteinase 19 (MMP19) is a member of zinc-dependent endopeptidases, which have been involved in various physiological and pathological processes. Its expression has been demonstrated in some types of cancers, but the clinical significance of MMP19 in colorectal cancer (CRC) has not been reported. Thus, we aimed to analyze the clinical significance of MMP19 in CRC in present study.

Methods

The expression of MMP19 was first explored in The Cancer Genome Atlas (TCGA) cohort, and then validated in the GSE39582 cohort and our own database. Clinicopathological features and survival rate were also investigated.

Results

MMP19 was found to be a predictor for overall survival (OS) in both univariate (hazard ratio [HR]: 1.449, 95% confidence interval [CI]: 1.108–1.893, P = 0.007) and multivariate survival analyses (HR: 1.401, 95% CI: 1.036–1.894, P = 0.028) in the TCGA database. MMP19 was further validated as an independent factor for recurrence free survival in the GSE39582 database by both univariate analysis (HR: 2.061, 95%CI: 1.454–2.921, P < 0.001) and multivariate analysis (HR = 1.470, 95% CI: 1.025–2.215, P = 0.032). In an in-house cohort, MMP19 was significantly upregulated in CRC tissues when compared with their adjacent normal controls (P < 0.001). Ectopic MMP19 expression was positively associated with lymph node metastases (P = 0.029), intramural vascular invasion (P = 0.015) and serum carcinoembryonic antigen levels (P = 0.045). High MMP19 expression correlated with a shorter OS (HR = 5.595; 95% CI: 2.573–12.164; P < 0.001) and disease free survival (HR = 4.699; 95% CI: 2.461–8.974; P < 0.001) in multivariate cox regression analysis.

Conclusions

Expression of MMP19 was upregulated in CRC. High expression of MMP19 was determined to be an independent and poor prognostic factor in CRC. These results suggest that MMP19 may be a good biomarker for CRC.
Literature
1.
go back to reference Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93.
2.
go back to reference Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef
3.
go back to reference Peng J, Ou Q, Guo J, Pan Z, Zhang R, Wu X, Zhao Y, Deng Y, Li C, Wang F et al. Expression of a novel CNPY2 isoform in colorectal cancer and its association with oncologic prognosis. Aging 2017;9(11):2334–51.CrossRef Peng J, Ou Q, Guo J, Pan Z, Zhang R, Wu X, Zhao Y, Deng Y, Li C, Wang F et al. Expression of a novel CNPY2 isoform in colorectal cancer and its association with oncologic prognosis. Aging 2017;9(11):2334–51.CrossRef
4.
go back to reference Van Cutsem E, Nordlinger B, Cervantes A, Group EGW. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol. 2010;21(Suppl 5):v93–7.CrossRef Van Cutsem E, Nordlinger B, Cervantes A, Group EGW. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol. 2010;21(Suppl 5):v93–7.CrossRef
5.
go back to reference Jacob H, Stanisavljevic L, Storli KE, Hestetun KE, Dahl O, Myklebust MP. Identification of a sixteen-microRNA signature as prognostic biomarker for stage II and III colon cancer. Oncotarget. 2017;8(50):87837–47.CrossRef Jacob H, Stanisavljevic L, Storli KE, Hestetun KE, Dahl O, Myklebust MP. Identification of a sixteen-microRNA signature as prognostic biomarker for stage II and III colon cancer. Oncotarget. 2017;8(50):87837–47.CrossRef
6.
go back to reference Osumi H, Shinozaki E, Suenaga M, Matsusaka S, Konishi T, Akiyoshi T, Fujimoto Y, Nagayama S, Fukunaga Y, Ueno M, et al. RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. Int J Cancer. 2016;139(4):803–11.CrossRef Osumi H, Shinozaki E, Suenaga M, Matsusaka S, Konishi T, Akiyoshi T, Fujimoto Y, Nagayama S, Fukunaga Y, Ueno M, et al. RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. Int J Cancer. 2016;139(4):803–11.CrossRef
7.
go back to reference Nakaji Y, Oki E, Nakanishi R, Ando K, Sugiyama M, Nakashima Y, Yamashita N, Saeki H, Oda Y, Maehara Y. Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer. J Cancer Res Clin Oncol. 2017;143(1):151–60.CrossRef Nakaji Y, Oki E, Nakanishi R, Ando K, Sugiyama M, Nakashima Y, Yamashita N, Saeki H, Oda Y, Maehara Y. Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer. J Cancer Res Clin Oncol. 2017;143(1):151–60.CrossRef
8.
go back to reference Sinicrope FA, Mahoney MR, Smyrk TC, Thibodeau SN, Warren RS, Bertagnolli MM, Nelson GD, Goldberg RM, Sargent DJ, Alberts SR. Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol. 2013;31(29):3664–72.CrossRef Sinicrope FA, Mahoney MR, Smyrk TC, Thibodeau SN, Warren RS, Bertagnolli MM, Nelson GD, Goldberg RM, Sargent DJ, Alberts SR. Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol. 2013;31(29):3664–72.CrossRef
9.
go back to reference Alaseem A, Alhazzani K, Dondapati P, Alobid S, Bishayee A, Rathinavelu A. Matrix Metalloproteinases: A challenging paradigm of cancer management. Seminars in cancer biology 2017;S1044-579X (17)30184–0. Alaseem A, Alhazzani K, Dondapati P, Alobid S, Bishayee A, Rathinavelu A. Matrix Metalloproteinases: A challenging paradigm of cancer management. Seminars in cancer biology 2017;S1044-579X (17)30184–0.
10.
go back to reference Brown GT, Murray GI. Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 2015;237(3):273–81.CrossRef Brown GT, Murray GI. Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 2015;237(3):273–81.CrossRef
11.
go back to reference Cao L, Chen C, Zhu H, Gu X, Deng D, Tian X, Liu J, Xiao Q,.MMP16 is a marker of poor prognosis in gastric cancer promoting proliferation and invasion. Oncotarget 2016;7(32):51865–74. Cao L, Chen C, Zhu H, Gu X, Deng D, Tian X, Liu J, Xiao Q,.MMP16 is a marker of poor prognosis in gastric cancer promoting proliferation and invasion. Oncotarget 2016;7(32):51865–74.
12.
go back to reference Arii S, Mise M, Harada T, Furutani M, Ishigami S, Niwano M, Mizumoto M, Fukumoto M, Imamura M. Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential. Hepatology. 1996;24(2):316–22.CrossRef Arii S, Mise M, Harada T, Furutani M, Ishigami S, Niwano M, Mizumoto M, Fukumoto M, Imamura M. Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential. Hepatology. 1996;24(2):316–22.CrossRef
13.
go back to reference Dong Y, Chen G, Gao M, Tian X. Increased expression of MMP14 correlates with the poor prognosis of Chinese patients with gastric cancer. Gene. 2015;563(1):29–34.CrossRef Dong Y, Chen G, Gao M, Tian X. Increased expression of MMP14 correlates with the poor prognosis of Chinese patients with gastric cancer. Gene. 2015;563(1):29–34.CrossRef
14.
go back to reference Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10(24):8229–34.CrossRef Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10(24):8229–34.CrossRef
15.
go back to reference Cui G, Cai F, Ding Z, Gao L. MMP14 predicts a poor prognosis in patients with colorectal cancer. Hum Pathol. 2019;83:36–42.CrossRef Cui G, Cai F, Ding Z, Gao L. MMP14 predicts a poor prognosis in patients with colorectal cancer. Hum Pathol. 2019;83:36–42.CrossRef
16.
go back to reference Sedlacek R, Mauch S, Kolb B, Schatzlein C, Eibel H, Peter HH, Schmitt J, Krawinkel U. Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology. 1998;198(4):408–23.CrossRef Sedlacek R, Mauch S, Kolb B, Schatzlein C, Eibel H, Peter HH, Schmitt J, Krawinkel U. Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology. 1998;198(4):408–23.CrossRef
17.
go back to reference Chan KC, Ko JM, Lung HL, Sedlacek R, Zhang ZF, Luo DZ, Feng ZB, Chen S, Chen H, Chan KW, et al. Catalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma. Int J Cancer. 2011;129(8):1826–37.CrossRef Chan KC, Ko JM, Lung HL, Sedlacek R, Zhang ZF, Luo DZ, Feng ZB, Chen S, Chen H, Chan KW, et al. Catalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma. Int J Cancer. 2011;129(8):1826–37.CrossRef
18.
go back to reference Pendas AM, Knauper V, Puente XS, Llano E, Mattei MG, Apte S, Murphy G, Lopez-Otin C. Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution. J Biol Chem. 1997;272(7):4281–6.CrossRef Pendas AM, Knauper V, Puente XS, Llano E, Mattei MG, Apte S, Murphy G, Lopez-Otin C. Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution. J Biol Chem. 1997;272(7):4281–6.CrossRef
19.
go back to reference Li Y, Jia H, Yu W, Xu Y, Li X, Li Q, Cai S. Nomograms for predicting prognostic value of inflammatory biomarkers in colorectal cancer patients after radical resection. Int J Cancer. 2016;139(1):220–31.CrossRef Li Y, Jia H, Yu W, Xu Y, Li X, Li Q, Cai S. Nomograms for predicting prognostic value of inflammatory biomarkers in colorectal cancer patients after radical resection. Int J Cancer. 2016;139(1):220–31.CrossRef
20.
go back to reference Li Q, Qin Y, Wei P, Lian P, Li Y, Xu Y, Li X, Li D, Cai S. Gas1 inhibits metastatic and metabolic phenotypes in colorectal carcinoma. Mol Cancer Res. 2016;14(9):830–40.CrossRef Li Q, Qin Y, Wei P, Lian P, Li Y, Xu Y, Li X, Li D, Cai S. Gas1 inhibits metastatic and metabolic phenotypes in colorectal carcinoma. Mol Cancer Res. 2016;14(9):830–40.CrossRef
21.
go back to reference Jiang Z, Yu T, Fan Z, Yang H, Lin X. Kruppel-like factor 7 is a marker of aggressive gastric Cancer and poor prognosis. Cell Physiol Biochem. 2017;43(3):1090–9.CrossRef Jiang Z, Yu T, Fan Z, Yang H, Lin X. Kruppel-like factor 7 is a marker of aggressive gastric Cancer and poor prognosis. Cell Physiol Biochem. 2017;43(3):1090–9.CrossRef
22.
go back to reference Wu G, Yuan S, Chen Z, Chen G, Fan Q, Dong H, Ye F, Li J, Zhu X. The KLF14 transcription factor regulates glycolysis by Downregulating LDHB in colorectal Cancer. Int J Biol Sci. 2019;15(3):628–35.CrossRef Wu G, Yuan S, Chen Z, Chen G, Fan Q, Dong H, Ye F, Li J, Zhu X. The KLF14 transcription factor regulates glycolysis by Downregulating LDHB in colorectal Cancer. Int J Biol Sci. 2019;15(3):628–35.CrossRef
23.
go back to reference Li Q, Qin Y, Wei P, Lian P, Li Y, Xu Y, Li X, Li D, Cai S. Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma. Molecular cancer research : MCR 2016;14(9):830–40.CrossRef Li Q, Qin Y, Wei P, Lian P, Li Y, Xu Y, Li X, Li D, Cai S. Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma. Molecular cancer research : MCR 2016;14(9):830–40.CrossRef
24.
go back to reference Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.CrossRef Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.CrossRef
25.
go back to reference Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, et al. Matrix metalloproteinase-19 promotes metastatic behavior in vitro and is associated with increased mortality in non-small cell lung cancer. Am J Respir Crit Care Med. 2014;190(7):780–90.CrossRef Yu G, Herazo-Maya JD, Nukui T, Romkes M, Parwani A, Juan-Guardela BM, Robertson J, Gauldie J, Siegfried JM, Kaminski N, et al. Matrix metalloproteinase-19 promotes metastatic behavior in vitro and is associated with increased mortality in non-small cell lung cancer. Am J Respir Crit Care Med. 2014;190(7):780–90.CrossRef
26.
go back to reference Muller M, Beck IM, Gadesmann J, Karschuk N, Paschen A, Proksch E, Djonov V, Reiss K, Sedlacek R. MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells. Modern Pathol. 2010;23(4):511–21.CrossRef Muller M, Beck IM, Gadesmann J, Karschuk N, Paschen A, Proksch E, Djonov V, Reiss K, Sedlacek R. MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells. Modern Pathol. 2010;23(4):511–21.CrossRef
27.
go back to reference Lettau I, Hattermann K, Held-Feindt J, Brauer R, Sedlacek R, Mentlein R. Matrix metalloproteinase-19 is highly expressed in astroglial tumors and promotes invasion of glioma cells. J Neuropathol Exp Neurol. 2010;69(3):215–23.CrossRef Lettau I, Hattermann K, Held-Feindt J, Brauer R, Sedlacek R, Mentlein R. Matrix metalloproteinase-19 is highly expressed in astroglial tumors and promotes invasion of glioma cells. J Neuropathol Exp Neurol. 2010;69(3):215–23.CrossRef
28.
go back to reference Sena P, Mariani F, Marzona L, Benincasa M, Ponz de Leon M, Palumbo C, Roncucci L. Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages. Int J Oncol. 2012;41(1):260–6.PubMed Sena P, Mariani F, Marzona L, Benincasa M, Ponz de Leon M, Palumbo C, Roncucci L. Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages. Int J Oncol. 2012;41(1):260–6.PubMed
Metadata
Title
High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer
Authors
Zaiping Chen
Guiyang Wu
Fubo Ye
Guoping Chen
Qinghao Fan
Hao Dong
Xiongwen Zhu
Chongshan Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5673-6

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