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The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Year 2018, Volume: 2 Issue: 1, 7 - 14, 01.03.2018
https://doi.org/10.30621/jbachs.2018.259

Abstract

Purpose: Colorectal cancer CRC is one of the most common and death related cancers in the world. Therefore, the early diagnosis of CRC remains with a great importance to prevent its further progression and increase survival rates. Colonoscopy and pathological examinations which are invasive and painful procedures, are needed to make a definitive diagnosis of CRC. The carcinoembryonic antigen CEA is particularly used for postoperative follow-up of CRC patients. The imbalance between matrix metalloproteinases MMPs and their tissue inhibitors of metalloproteinases TIMPs leads to degradation of extracellular matrix which is the most important step in invasion and metastasis. It was also observed that cyclooxygenase-2 COX-2 has crucial roles in the development and progression of colorectal cancer. The purpose of our study is to detect fecal and plasma MMP-7, COX-2, TIMP-1, and CEA protein levels in patients with colorectal cancer, colorectal polyps, and healthy individuals, and assess their association with each other and with clinicopathological variables. We also aimed to evaluate plasma and fecal MMP-7, COX-2, TIMP-1, and CEA protein levels as potential diagnostic markers in colorectal carcinoma.Methods: Plasma and fecal samples were taken from patients with fifteen colorectal cancers, twenty-six colorectal polyps, and thirty-three healthy volunteers. Protein extraction was carried out from fecal samples. Plasma and fecal MMP-7, TIMP-1, and COX-2 protein levels were determined by ELISA whereas plasma and fecal CEA protein levels were detected with CEIA.Results: Plasma and fecal CEA levels were significantly higher in CRC than the control. In addition, plasma TIMP-1 and plasma CEA levels were significantly elevated in cancer according to polyp group. We also detected decreased plasma MMP-7 levels in polyps compared to control group. Positive correlations were observed among plasma COX-2 and TIMP-1 levels r=0.571 , fecal COX-2 and CEA levels r=0.764 in CRC. However, no association was found between biochemical parameters and clinicopathological variables. ROC analysis for discriminating CRC from healthy controls showed that area under curves AUC for fecal and plasma CEA levels were 0.763 and 0.692, respectively. Plasma CEA AUC=0.735 , plasma TIMP-1 AUC=0.706 , and their combination AUC=0.760 exhibited significant diagnostic performances to differentiate CRC from polyp. In discrimination colorectal polyps from healthy tissues, MMP-7 showed the highest AUC value 0.667 .Conclusion: Here we suggested that plasma and fecal CEA protein levels may be potential predictive noninvasive markers for diagnosis of colorectal adenocarcinoma. In addition, plasma CEA and TIMP-1 are also valuable biomarker candidates in differentiating colorectal cancer from colorectal polyps

References

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  • Edwards BK, Howe HL, Ries LA, et al. Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U. S. cancer burden. Cancer 2002;94:2766–2792.
  • Hundt S, Haug U, Brenner H. Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev 2007;16:1935–1953. [CrossRef]
  • Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res 1999;59:3313–3316.
  • Aihara R, Mochiki E, Nakabayashi T, Akazawa K, Asao T, Kuwano H. Clinical significance of mucin phenotype, beta-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma. Br J Surg 2005;92:454–462. [CrossRef]
  • Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y, Imai K. Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut 1999;45:252–258.
  • Yamamoto H, Itoh F, Iku S, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 2001;19:1118–1127. [CrossRef]
  • Takeuchi N, Ichikawa Y, Ishikawa T, et al. Matrilysin gene expression in sporadic and familial colorectal adenomas. Mol Carcinog 1997;19:225–229.
  • Tomita T, Iwata K. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in colonic adenomas-adenocarcinomas. Dis Colon Rectum 1996;39:1255–1264.
  • Chandrasekharan NV, Simmons DL. The cyclooxygenases. Genome Biol 2004;5(9):241. [CrossRef]
  • Dubois MA, Sabatier P, Durand B, Calavas D, Ducrot C, Chalvet- Monfray K. Multiplicative genetic effects in scrapie disease susceptibility. C R Biol 2002;325:565–570.
  • Nastase A, Paslaru L, Niculescu AM, et al. Prognostic and predictive potential molecular biomarkers in colon cancer. Chirurgia (Bucur) 2011;106:177–185.
  • Keles D, Arslan B, Terzi C, et al. Expression and activity levels of matrix metalloproteinase-7 and in situ localization of caseinolytic activity in colorectal cancer. Clin Biochem 2014;47:1265–1271. [CrossRef]
  • Maurel J, Nadal C, Garcia-Albeniz X, et al. Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 2007;121:1066–1071. [CrossRef]
  • Waas ET, Hendriks T, Lomme RM, Wobbes T. Plasma levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 correlate with disease stage and survival in colorectal cancer patients. Dis Colon Rectum 2005;48:700–710.
  • Giaginis C, Nikiteas N, Margeli A, et al. Serum tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) levels in colorectal cancer patients: associations with clinicopathological variables and patient survival. Int J Biol Markers 2009;24:245–252.
  • Holten-Andersen MN, Fenger C, Nielsen HJ, et al. Plasma TIMP-1 in patients with colorectal adenomas: a prospective study. Eur J Cancer 2004;40:2159–2164. [CrossRef]
  • Holten-Andersen MN, Stephens RW, Nielsen HJ, et al. High preoperative plasma tissue inhibitor of metalloproteinase-1 levels are associated with short survival of patients with colorectal cancer. Clin Cancer Res 2000;6:4292–4299.
  • Kawasaki T, Nosho K, Ohnishi M, et al. Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma. BMC Cancer 2008;8:33. [CrossRef]
  • Wasilewicz MP, Kolodziej B, Bojulko T, Kaczmarczyk M, Sulzyc- Bielicka V, Bielicki D. Expression of cyclooxygenase-2 in colonic polyps. Pol Arch Med Wewn 2010;120:313–320.
  • Han YD, Hong YK, Kang JG, Choi YJ, Park Ch. Relation of the expression of cyclooxygenase-2 in colorectal adenomas and adenocarcinomas to angiogenesis and prognosis. J Korean Soc Coloproctol 2010;26:339– 346. [CrossRef]
  • Wang WS, Lin JK, Chiou TJ, et al. Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience. Jpn J Clin Oncol 2000;30:12–16.
  • Irvine T, Scott M, Clark CI. A small rise in CEA is sensitive for recurrence after surgery for colorectal cancer. Colorectal Dis 2007;9:527–531. [CrossRef]
  • Stubbs RS, Nadkarni DM, Monsey HA. Faecal carcinoembryonic antigen in colorectal cancer patients. Gut 1986;27:901–905.
  • Sugano K, Ohkura H, Hirohashi S, et al. Detection of increased fecal carcinoembryonic antigen and its characterization as a membrane- bound form in colorectal carcinoma and other gastrointestinal disorders. Jpn J Cancer Res 1989;80:1156–1160.
  • Kim Y, Lee S, Park S, et al. Gastrointestinal tract cancer screening using fecal carcinoembryonic antigen. Ann Clin Lab Sci 2003;33:32–38.
  • Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365–1371. [CrossRef]
  • Ransohoff DF, Lang CA. Screening for colorectal cancer with the fecal occult blood test: a background paper. American College of Physicians. Ann Intern Med 1997;126:811–822.
  • Takai T, Kanaoka S, Yoshida K, et al. Fecal cyclooxygenase 2 plus matrix metalloproteinase 7 mRNA assays as a marker for colorectal cancer screening. Cancer Epidemiol Biomarkers Prev 2009;18:1888– 1893. [CrossRef]
  • Karl J, Wild N, Tacke M, et al. Improved diagnosis of colorectal cancer using a combination of fecal occult blood and novel fecal protein markers. Clin Gastroenterol Hepatol 2008;6:1122–1128. [CrossRef]
  • Hamaya Y, Yoshida K, Takai T, et al. Factors that contribute to faecal cyclooxygenase-2 mRNA expression in subjects with colorectal cancer. Br J Cancer 2010;102:916–921. [CrossRef]
  • Mroczko B, Groblewska M, Okulczyk B, Kedra B, Szmitkowski M. The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients. Int J Colorectal Dis 2010;25:1177–1184. [CrossRef]
Year 2018, Volume: 2 Issue: 1, 7 - 14, 01.03.2018
https://doi.org/10.30621/jbachs.2018.259

Abstract

References

  • Ries LA, Wingo PA, Miller DS, et al. The annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer. Cancer 2000;88:2398–2424.
  • Edwards BK, Howe HL, Ries LA, et al. Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U. S. cancer burden. Cancer 2002;94:2766–2792.
  • Hundt S, Haug U, Brenner H. Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev 2007;16:1935–1953. [CrossRef]
  • Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res 1999;59:3313–3316.
  • Aihara R, Mochiki E, Nakabayashi T, Akazawa K, Asao T, Kuwano H. Clinical significance of mucin phenotype, beta-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma. Br J Surg 2005;92:454–462. [CrossRef]
  • Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y, Imai K. Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut 1999;45:252–258.
  • Yamamoto H, Itoh F, Iku S, et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 2001;19:1118–1127. [CrossRef]
  • Takeuchi N, Ichikawa Y, Ishikawa T, et al. Matrilysin gene expression in sporadic and familial colorectal adenomas. Mol Carcinog 1997;19:225–229.
  • Tomita T, Iwata K. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in colonic adenomas-adenocarcinomas. Dis Colon Rectum 1996;39:1255–1264.
  • Chandrasekharan NV, Simmons DL. The cyclooxygenases. Genome Biol 2004;5(9):241. [CrossRef]
  • Dubois MA, Sabatier P, Durand B, Calavas D, Ducrot C, Chalvet- Monfray K. Multiplicative genetic effects in scrapie disease susceptibility. C R Biol 2002;325:565–570.
  • Nastase A, Paslaru L, Niculescu AM, et al. Prognostic and predictive potential molecular biomarkers in colon cancer. Chirurgia (Bucur) 2011;106:177–185.
  • Keles D, Arslan B, Terzi C, et al. Expression and activity levels of matrix metalloproteinase-7 and in situ localization of caseinolytic activity in colorectal cancer. Clin Biochem 2014;47:1265–1271. [CrossRef]
  • Maurel J, Nadal C, Garcia-Albeniz X, et al. Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 2007;121:1066–1071. [CrossRef]
  • Waas ET, Hendriks T, Lomme RM, Wobbes T. Plasma levels of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 correlate with disease stage and survival in colorectal cancer patients. Dis Colon Rectum 2005;48:700–710.
  • Giaginis C, Nikiteas N, Margeli A, et al. Serum tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) levels in colorectal cancer patients: associations with clinicopathological variables and patient survival. Int J Biol Markers 2009;24:245–252.
  • Holten-Andersen MN, Fenger C, Nielsen HJ, et al. Plasma TIMP-1 in patients with colorectal adenomas: a prospective study. Eur J Cancer 2004;40:2159–2164. [CrossRef]
  • Holten-Andersen MN, Stephens RW, Nielsen HJ, et al. High preoperative plasma tissue inhibitor of metalloproteinase-1 levels are associated with short survival of patients with colorectal cancer. Clin Cancer Res 2000;6:4292–4299.
  • Kawasaki T, Nosho K, Ohnishi M, et al. Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma. BMC Cancer 2008;8:33. [CrossRef]
  • Wasilewicz MP, Kolodziej B, Bojulko T, Kaczmarczyk M, Sulzyc- Bielicka V, Bielicki D. Expression of cyclooxygenase-2 in colonic polyps. Pol Arch Med Wewn 2010;120:313–320.
  • Han YD, Hong YK, Kang JG, Choi YJ, Park Ch. Relation of the expression of cyclooxygenase-2 in colorectal adenomas and adenocarcinomas to angiogenesis and prognosis. J Korean Soc Coloproctol 2010;26:339– 346. [CrossRef]
  • Wang WS, Lin JK, Chiou TJ, et al. Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience. Jpn J Clin Oncol 2000;30:12–16.
  • Irvine T, Scott M, Clark CI. A small rise in CEA is sensitive for recurrence after surgery for colorectal cancer. Colorectal Dis 2007;9:527–531. [CrossRef]
  • Stubbs RS, Nadkarni DM, Monsey HA. Faecal carcinoembryonic antigen in colorectal cancer patients. Gut 1986;27:901–905.
  • Sugano K, Ohkura H, Hirohashi S, et al. Detection of increased fecal carcinoembryonic antigen and its characterization as a membrane- bound form in colorectal carcinoma and other gastrointestinal disorders. Jpn J Cancer Res 1989;80:1156–1160.
  • Kim Y, Lee S, Park S, et al. Gastrointestinal tract cancer screening using fecal carcinoembryonic antigen. Ann Clin Lab Sci 2003;33:32–38.
  • Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365–1371. [CrossRef]
  • Ransohoff DF, Lang CA. Screening for colorectal cancer with the fecal occult blood test: a background paper. American College of Physicians. Ann Intern Med 1997;126:811–822.
  • Takai T, Kanaoka S, Yoshida K, et al. Fecal cyclooxygenase 2 plus matrix metalloproteinase 7 mRNA assays as a marker for colorectal cancer screening. Cancer Epidemiol Biomarkers Prev 2009;18:1888– 1893. [CrossRef]
  • Karl J, Wild N, Tacke M, et al. Improved diagnosis of colorectal cancer using a combination of fecal occult blood and novel fecal protein markers. Clin Gastroenterol Hepatol 2008;6:1122–1128. [CrossRef]
  • Hamaya Y, Yoshida K, Takai T, et al. Factors that contribute to faecal cyclooxygenase-2 mRNA expression in subjects with colorectal cancer. Br J Cancer 2010;102:916–921. [CrossRef]
  • Mroczko B, Groblewska M, Okulczyk B, Kedra B, Szmitkowski M. The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients. Int J Colorectal Dis 2010;25:1177–1184. [CrossRef]
There are 32 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Rabia Kıyak This is me

Didem Keleş This is me

Göksel Bengi This is me

Mustafa Yalçın This is me

Ömer Topalak This is me

Gülgün Oktay This is me

Publication Date March 1, 2018
Published in Issue Year 2018 Volume: 2 Issue: 1

Cite

APA Kıyak, R., Keleş, D., Bengi, G., Yalçın, M., et al. (2018). The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer. Journal of Basic and Clinical Health Sciences, 2(1), 7-14. https://doi.org/10.30621/jbachs.2018.259
AMA Kıyak R, Keleş D, Bengi G, Yalçın M, Topalak Ö, Oktay G. The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer. JBACHS. March 2018;2(1):7-14. doi:10.30621/jbachs.2018.259
Chicago Kıyak, Rabia, Didem Keleş, Göksel Bengi, Mustafa Yalçın, Ömer Topalak, and Gülgün Oktay. “The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer”. Journal of Basic and Clinical Health Sciences 2, no. 1 (March 2018): 7-14. https://doi.org/10.30621/jbachs.2018.259.
EndNote Kıyak R, Keleş D, Bengi G, Yalçın M, Topalak Ö, Oktay G (March 1, 2018) The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer. Journal of Basic and Clinical Health Sciences 2 1 7–14.
IEEE R. Kıyak, D. Keleş, G. Bengi, M. Yalçın, Ö. Topalak, and G. Oktay, “The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer”, JBACHS, vol. 2, no. 1, pp. 7–14, 2018, doi: 10.30621/jbachs.2018.259.
ISNAD Kıyak, Rabia et al. “The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer”. Journal of Basic and Clinical Health Sciences 2/1 (March 2018), 7-14. https://doi.org/10.30621/jbachs.2018.259.
JAMA Kıyak R, Keleş D, Bengi G, Yalçın M, Topalak Ö, Oktay G. The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer. JBACHS. 2018;2:7–14.
MLA Kıyak, Rabia et al. “The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer”. Journal of Basic and Clinical Health Sciences, vol. 2, no. 1, 2018, pp. 7-14, doi:10.30621/jbachs.2018.259.
Vancouver Kıyak R, Keleş D, Bengi G, Yalçın M, Topalak Ö, Oktay G. The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer. JBACHS. 2018;2(1):7-14.