Aim To determine the serum levels of matrix metalloproteinase 9 (MMP-9) concentration and their association with the stage and histopathologic sizes of colorectal cancer (CRC). Methods One hundred and two patients with clinically diagnosed and histologically confirmed colorectal cancer ready for surgical treatment were included in the study. In each patient, preoperative peripheral venous blood samples were taken for determination of the concentration of MMP-9 using ELISA immunoassay test. Resected tumour specimens were studied pathologically according to the criteria of the TNM classification. All patients were divided into groups according to the TNM classification. The control group presented 30 subjects of the appropriate age and gender with no family history of cancer, clinical signs of malignancy or inflammatory bowel disease. Results The serum levels of MMP-9 were progressively increased in patients with CRC reaching the highest value in the fourth stage of CRC. It was also confirmed that the serum concentrations of MMP-9 were significantly higher in patients with pericolonic lymph nodes involvement compared to the patients with no involvement of lymph nodes, 456.4 (445.9-464.7) ng/mL vs. 438.4 (418.4-447.8) ng/mL (p<0.001). Significantly higher serum levels of MMP-9 were found in the patients with metastatic CRC, 458.5 (452.0-468.1) ng/mL compared with the CRC patients without metastasis, 445.8 (436.9-456.5) ng/mL (p<0.001). Conclusion It was confirmed that serum concentration of MMP-9 presented the significant independent risk factors for the progression of CRC.
Siegel R, Miller K, Jemal A. Cancer statistics. CA Cancer J Clin. 2016;7–30.
2.
Malvezzi M, Bertuccio P, Rosso T, Rota M, Levi F, Vecchia L, et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol. 2015;779–86.
3.
Fearonn E, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;759–67.
4.
Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interac. 2006;1–40.
5.
Gopčević K, Rovčanin B, Tatić S, Krivokapić Z, Gajić M, Dragutinović V. Activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in different stages of colorectal carcinoma. Dig Dis Sci. 2013;2646–52.
6.
Herszényi L, Barabás L, Hritz I, István G, Tulassay Z. Impact of proteolytic enzymes in colorectal cancer development and progression. World J Gastroenterol. 2014;13246–57.
7.
Iyer R, Patterson N, Fields G, Lindsey M. The history of matrix metalloproteinases: milestones, myths, and misperceptions. Am J Physiol Heart Circ Physiol. 2012;919–30.
8.
Roy R, Yang J, Moses M. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clinl Oncol. 2009;5287–97.
9.
Hong S, Kang Y, Lee B, Lee W, Jang Y, Paik I, et al. Matrix metalloproteinase-2 and -7 expression in colorectal cancer. J Korean Soc Coloproctol. 2011;133–9.
10.
El-Badrawy M, Yousef A, Shaalan D, Elsamanoudy A. Matrix metalloproteinase-9 expression in lung cancer patients and its relation to serum MMP-9 activity, pathologic type, and prognosis. J Bronchology Interv Pulmonol. 2014;327–34.
11.
Mroczko B, Lukaszewicz-Zajac M, Wereszczynska-Siemiatkowska U, Groblewska M, Gryko M, Kedra B, et al. Clinical significance of the measurements of serum matrix metalloproteinase-9 and its inhibitor (tissue inhibitor of metalloproteinase-1) in patients with pancreatic cancer: metalloproteinase-9 as an independent prognostic factor. Pancreas. 2009;613–8.
12.
Zhang W, Hu X, -X, Yang XZ, Wang Q, Cheng H, et al. Combined detection of serum matrix metalloproteinase 9, acetyl heparinase and cathepsin L in diagnosis of ovarian cancer. Chin J Cancer Res. 2012;67–71.
13.
Zhang L, Shi J, Feng J, Klocker H, Lee C, Zhang J. Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer. Prostate Cancer Prostatic Dis. 2004;327–32.
14.
FUNDING No specific funding was received for this study. TRANSPARENCY DECLARATIONS Competing interests: none to declare.
15.
Provatopoulou X, Gounaris A, Kalogera E, Zagouri F, Flessas I, Goussetis E, et al. Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/ NGAL in breast cancer disease. BMC Cancer. 2009;390.
16.
Hormigo A, Gu B, Karimi S, Riedel E, Panageas K, Edgar M, et al. YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res. 2017;1422–31.
17.
Herszényi L, Hritz I, Lakatos G, Varga M, Tulassay Z. The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci. 2012;13240–63.
18.
Yang B, Su K, Gao J, Rao Z. Expression and prognostic value of matrix metalloproteinase-7 in colorectal cancer. Asian Pac J Cancer Prev. 2012;1049–52.
19.
Hurst N, Stocken D, Wilson S, Keh C, Wakelam M, Ismail T. Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients. Br J Cancer. 2007;971–7.
20.
Wilson S, Damery S, Stocken D, Dowswell G, Holder R, Ward S, et al. Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test. Br J Cancer. 2012;1431–8.
21.
Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;52–67.
22.
Chu D, Zhao Z, Zhou Y, Li Y, Li J, Zheng J, et al. Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 2012;318–25.
23.
Emara M, Cheung PY, Grabowski K, Sawicki G, Wozniak M. Serum levels of matrix metalloproteinase-2 and -9 and conventional tumor markers (CEA and CA 19-9) in patients with colorectal and gastric cancers. Clin Chem Lab Med. 2009;993–1000.
24.
Hamilton S, Aaltonen L. Pathology and Genetics of Tumours of the Digestive System. 2000;104.
25.
Edge S, Byrd D, Compton C, Fritz A, Greene F, Trotti A. AJCC cancer staging manual. 2010;(7).
26.
Sun J. Matrix metalloproteinases and tissue inhibitor of metalloproteinases are essential for the inflammatory response in cancer cells. J Signal Transduct. 2010;985132.
27.
Bendardaf R, Lamlum H, Pyrhönen S. Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res. 2004;2519–30.
28.
Vihinen P, Kähäri V. Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer. 2002;157–66.
29.
Biasi F, Guina T, Maina M, Nano M, Falcone A, Aroasio E, et al. Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract. PLoS ONE. 2012;41839.
30.
Talmadge J, Fidler I. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010;5649–69.
31.
Damery S, Nichols L, Holder R, Ward S, Warmington S, Wilson S, et al. Assessing the value of matrix metalloproteinase 9 (MMP9) in improving the appropriateness of referrals for colorectal cancer. Br J Cancer. 2013;1149–56.
32.
Jonsson A, Hjalmarsson C, Falk P, Ivarsson M. Levels of matrix metalloproteinases differ in plasma and serum -aspects regarding analysis of biological markers in cancer. Br J Cancer. 2016;703–6.
33.
Herszényi L, Hritz I, Lakatos G, Varga M, Tulassay Z. The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci. 2012;13240–63.
34.
Ting W, Chen L, Pao J, Yang Y, You B, Chang T, et al. Genetic polymorphisms of matrix metalloproteinases and clinical outcomes in colorectal cancer patients. Int J Med Sci. 2013;1022–7.
35.
Asano T, Tada M, Cheng S, Takemato N, Kuramae T, Abe M, et al. Prognostic values of matrix metalloproteinase family expression in human colorectal carcinoma. J Surg Res. 2008;32–42.
36.
Van Der Jagt M, Wobbes T, Strobbe L, Sweep F, Span P. Metalloproteinases and their regulators in colorectal cancer. J Surg Oncol. 2010;259–69.
37.
Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004;101–17.
38.
Said A, Raufman JP, Xie G. The role of matrix metalloproteinases in colorectal cancer. Cancers. 2014;366–75.
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