Research Article
BibTex RIS Cite

Evaluation of Serum Cystatin C Levels And Its Relation with CEA, CA 19-9 in Patients with Gastric and Colorectal Cancer

Year 2020, Volume: 17 Issue: 3, 372 - 377, 25.12.2020
https://doi.org/10.35440/hutfd.689952

Abstract


Background: Cystatin C, a marker of kidney function, is thought to have inhibiting effects in tumor growth. In the study comparing serum concentrations of cystatin C among gastric, colorectal cancer patients, controls and determination of its relation between serum CEA and CA 19-9 levels are aimed.
Materials and Methods: Gastric cancer patients (n=35), colorectal cancer patients (n=35) and healthy subjects (n=40) without any known systemic disease were included in the study. None of the participants had previously known kidney disease, serum creatinine level out of reference interval or eGFR<60 mL/min. Serum CEA and CA 19-9 levels were analysed using chemiluminescence immunoassay on Beckman Coulter UniCel® DxI 800 Immunoassay System and cystatin C was analysed with particle-enhanced turbidimetric immunoassay on Roche Diagnostics Cobas® Modular P® analyzer.
Results: Cystatin C levels were significantly higher in patients’ sera (p<0.001) while there was no significant difference between groups for serum creatinine (p=0.571). Multivariate logistic regression analysis revealed that creatinine level and participation in the patient groups were the determinants of the elevated serum cystatin C concentration, respectively. Each 0.1 mg/dL elevation in creatinine level increased the possibility of having high cystatin C level 2.531 times (95% CI: 1.562-4.100). Besides the possibility of finding high cystatin C levels were 20.384 times more in the patient group (95% CI:2.992-142.196). No significant relation between CEA, CA 19-9 and cystatin C was observed when participation in patient groups, age, sex and creatinine concentration were taken into consideration (p>0.05).
Conclusion: Serum cystatin C concentrations of gastric and colorectal cancer patients may be affected due to the presence of cancer besides kidney function.

Project Number

Ankara Numune Eğitim ve Araştırma Hastanesi'nden 25/01/2012 tarih ve 2012-302 Karar no ile Etik Kurul onayı alınmıştır.

References

  • 1. Cancer Fact Sheet [Internet]. World Health Organization. 2018 [cited 31.01.2020]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer.
  • 2. Talieri M, Papadopoulou S, Scorilas A, Xynopoulos D, Arnogianaki N, Plataniotis G, et al. Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer letters. 2004;205(1):97-106.
  • 3. Chen S, Dong H, Yang S, Guo H. Cathepsins in digestive cancers. Oncotarget. 2017;8(25):41690.
  • 4. Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2012;1824(1):68-88.
  • 5. George JA, Gounden V. Novel glomerular filtration markers. Advances in clinical chemistry. 88: Elsevier; 2019. p. 91-119.
  • 6. Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. The journal of medical investigation. 2005;52(1, 2):1-9.
  • 7. Kos J, Nielsen H-J, Krasovec M, Christensen IJ, Cimerman N, Stephens R, et al. Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients with colorectal cancer. Clinical cancer research. 1998;4(6):1511-6.
  • 8. Zeng Q, Zhao Y, Yang Y, Chen XX, Wang G, Zhang P, et al. Expression of Cystatin C in human stomach neoplasms. Molecular medicine reports. 2010;3(4):607-11.
  • 9. Saleh Y, Sebzda T, Warwas M, Kopec W, Ziólkowska J, Siewinski M. Expression of cystatin C in clinical human colorectal cancer tissues. Journal of experimental therapeutics & oncology. 2005;5(1).
  • 10. Bierie B, Moses HL. TGFβ: the molecular Jekyll and Hyde of cancer. Nature Reviews Cancer. 2006;6(7):506-20.
  • 11. Sokol JP, Schiemann WP. Cystatin C Antagonizes Transforming Growth Factor β Signaling in Normal and Cancer Cells11Start-up fund from the National Jewish Medical and Research Center and by a grant from the Elsa U. Pardee Foundation to W. Schiemann. Molecular cancer research. 2004;2(3):183-95.
  • 12. Kos J, S̆tabuc B, Cimerman N, Brünner N. Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clinical chemistry. 1998;44(12):2556-7.
  • 13. Nakai K, Kikuchi M, Fujimoto K, Kaneko Y, Omori S, Nakai K, et al. Serum levels of cystatin C in patients with malignancy. Clinical and experimental nephrology. 2008;12(2):132-9.
  • 14. Zhai H, Huang J, Yang C, Fu Y, Yang B. Serum CEA and CA19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia. Clinical laboratory. 2018;64(3):351-6.
  • 15. Shin JK, Kim HC, Lee WY, Yun SH, Cho YB, Huh JW, et al. High preoperative serum CA 19-9 levels can predict poor oncologic outcomes in colorectal cancer patients on propensity score analysis. Annals of surgical treatment and research. 2019;96(3):107-15.
  • 16. Saito H, Kono Y, Murakami Y, Kuroda H, Matsunaga T, Fukumoto Y, et al. Influence of prognostic nutritional index and tumor markers on survival in gastric cancer surgery patients. Langenbeck's archives of surgery. 2017;402(3):501-7.
  • 17. Bodnar L, Wcislo GB, Smoter M, Gasowska-Bodnar A, Stec R, Synowiec A, et al. Cystatin C as a parameter of glomerular filtration rate in patients with ovarian cancer. Kidney and Blood Pressure Research. 2010;33(5):360-7.
  • 18. Strojan P, Budihna M, Šmid L, Svetic B, Vrhovec I, Kos J, et al. Prognostic significance of cysteine proteinases cathepsins B and L and their endogenous inhibitors stefins A and B in patients with squamous cell carcinoma of the head and neck. Clinical Cancer Research. 2000;6(3):1052-62.
  • 19. Kos J, Lah TT. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer. Oncology reports. 1998;5(6):1349-410.
  • 20. Karcher D, McPherson R. Cerebrospinal, synovial, serous body fluids and alternative specimens. Henry’s clinical diagnosis and management by laboratory methods, 22th edition Richard A McPherson, Matthew R Pincus eds Elsevier Saunders, Philadelphia (PA). 2011:480-506.
  • 21. Herszényi L, Farinati F, Cardin R, István G, Molnár LD, Hritz I, et al. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer. BMC cancer. 2008;8(1):194.
  • 22. Štabuc B, Vrhovec L, Štabuc-Šilih M, Cizej TE. Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clinical chemistry. 2000;46(2):193-7.
  • 23. Kleber M, Cybulla M, Bauchmüller K, Ihorst G, Koch B, Engelhardt M. Monitoring of renal function in cancer patients: an ongoing challenge for clinical practice. Annals of oncology. 2007;18(5):950-8.
  • 24. Kos J, Krašovec M, Cimerman N, Nielsen HJ, Christensen IJ, Brünner N. Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clinical Cancer Research. 2000;6(2):505-11.
  • 25. Grubb AO. Cystatin C-properties and use as diagnostic marker. Advances in clinical chemistry. 2001;35:63-99.
  • 26. Massey D. Commentary: clinical diagnostic use of cystatin C. Journal of clinical laboratory analysis. 2004;18(1):55-60.
  • 27. Kos J, Stabuc B, Schweiger A, Krasovec M, Cimerman N, Kopitar-Jerala N, et al. Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clinical cancer research. 1997;3(10):1815-22.
  • 28. Kos J, Werle B, Lah T, Brunner N. Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. The International journal of biological markers. 2000;15(1):84-9.
  • 29. Zore I, Krasovec M, Cimerman N, Kuhelj R, Werle B, Nielsen HJ, et al. Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer. Biological chemistry. 2001;382(5):805-10.
  • 30. Iacobuzio-Donahue CA, Shuja S, Cai J, Peng P, Murnane MJ. Elevations in cathepsin B protein content and enzyme activity occur independently of glycosylation during colorectal tumor progression. Journal of Biological Chemistry. 1997;272(46):29190-9.

Mide ve Kolorektal Kanserli Hastalarda Serum Sistatin C Düzeyi ve CEA, CA 19-9 ile İlişkisinin İncelenmesi

Year 2020, Volume: 17 Issue: 3, 372 - 377, 25.12.2020
https://doi.org/10.35440/hutfd.689952

Abstract

Amaç: Böbrek fonksiyonun bir belirteci olarak bilinen sistatin C’nin tümör gelişiminde inhibör etki gösterdiği düşünülmektedir. Çalışmada bilinen böbrek hastalığı olmayan mide ve kolorektal kanserli olgularla sağlıklı bireylerin serum sistatin C düzeyleri arasındaki olası farkın, serum karsinoembriyonik antijen (CEA) ve karbohidrat antijen 19-9 (CA19-9) düzeyleri arasındaki ilişkinin incelenmesi amaçlanmıştır.
Materyal ve metod: Çalışmaya serum kreatinin konsantrasyonu referans aralığı içerisinde yer alan ve tahmini glomerüler filtrasyon hızı (eGFH) >60 mL/dk olan mide (n=35) ve kolorektal kanserli (n=35) hastalar ile bilinen herhangi bir sistemik hastalığı olmayan sağlıklı bireyler (n=40) dahil edilmiştir. CEA ve CA 19-9 testleri kemilüminesans temelli immün yöntemle (Beckman Coulter UniCel® DxI 800 Immunoassay System) Sistatin C analizi ise partikül yüzeyi genişletilmiş immünotürbidimetrik yöntem (Roche Diagnostics Cobas® Modular P®) kullanılarak yapılmıştır.
Bulgular: Mide, KRK (kolorektal kanser) ve kontrol grupları arasında serum kreatinin konsantrasyonu açısından önemli fark izlenmezken (p=0,571) sistatin C düzeyi hasta gruplarında kontrol grubuna göre anlamlı olarak daha yüksek izlenmiştir (p<0,001). Çoklu değişkenli lojistik regresyon analizinde sistatin C düzeyinin yüksek olması üzerinde sırasıyla; kreatinin düzeyi ve kanser hastası olmanın etkili olduğu bulunmuştur. Kreatinindeki her 0,1 mg/dL’lik artış sistatin C düzeyinin yüksek olma ihtimalini 2,531 kat (%95 güven aralığı: 1,562-4,100) arttırmaktadır (p<0,001). Ayrıca kontrol grubuna göre kanserli grupta sistatin C’nin yüksek olma ihtimalinin 20,384 kat (%95 güven aralığı: 2,992-142,196) fazla olduğu bulunmuştur (p=0,002). Hasta grubunda yer almak, yaş, cinsiyet ve kreatinin konsantrasyonu gibi faktörlerin etkileri göz önünde bulundurulduğunda CEA ve CA 19-9 yüksekliği ile serum sistatin C düzeyi arasında anlamlı ilişki izlenmemiştir (p>0,05).
Sonuç: Mide veya kolorektal kanserli olgularda serum sistatin C düzeyinin böbrek fonksiyonunun yanısıra kanser varlığından da etkilenebileceği gözlenmiştir.

Anahtar Kelimeler: Sistatin C, Katepsin, Mide Kanseri, Kolorektal Kanser

Project Number

Ankara Numune Eğitim ve Araştırma Hastanesi'nden 25/01/2012 tarih ve 2012-302 Karar no ile Etik Kurul onayı alınmıştır.

References

  • 1. Cancer Fact Sheet [Internet]. World Health Organization. 2018 [cited 31.01.2020]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer.
  • 2. Talieri M, Papadopoulou S, Scorilas A, Xynopoulos D, Arnogianaki N, Plataniotis G, et al. Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer letters. 2004;205(1):97-106.
  • 3. Chen S, Dong H, Yang S, Guo H. Cathepsins in digestive cancers. Oncotarget. 2017;8(25):41690.
  • 4. Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2012;1824(1):68-88.
  • 5. George JA, Gounden V. Novel glomerular filtration markers. Advances in clinical chemistry. 88: Elsevier; 2019. p. 91-119.
  • 6. Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. The journal of medical investigation. 2005;52(1, 2):1-9.
  • 7. Kos J, Nielsen H-J, Krasovec M, Christensen IJ, Cimerman N, Stephens R, et al. Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients with colorectal cancer. Clinical cancer research. 1998;4(6):1511-6.
  • 8. Zeng Q, Zhao Y, Yang Y, Chen XX, Wang G, Zhang P, et al. Expression of Cystatin C in human stomach neoplasms. Molecular medicine reports. 2010;3(4):607-11.
  • 9. Saleh Y, Sebzda T, Warwas M, Kopec W, Ziólkowska J, Siewinski M. Expression of cystatin C in clinical human colorectal cancer tissues. Journal of experimental therapeutics & oncology. 2005;5(1).
  • 10. Bierie B, Moses HL. TGFβ: the molecular Jekyll and Hyde of cancer. Nature Reviews Cancer. 2006;6(7):506-20.
  • 11. Sokol JP, Schiemann WP. Cystatin C Antagonizes Transforming Growth Factor β Signaling in Normal and Cancer Cells11Start-up fund from the National Jewish Medical and Research Center and by a grant from the Elsa U. Pardee Foundation to W. Schiemann. Molecular cancer research. 2004;2(3):183-95.
  • 12. Kos J, S̆tabuc B, Cimerman N, Brünner N. Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clinical chemistry. 1998;44(12):2556-7.
  • 13. Nakai K, Kikuchi M, Fujimoto K, Kaneko Y, Omori S, Nakai K, et al. Serum levels of cystatin C in patients with malignancy. Clinical and experimental nephrology. 2008;12(2):132-9.
  • 14. Zhai H, Huang J, Yang C, Fu Y, Yang B. Serum CEA and CA19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia. Clinical laboratory. 2018;64(3):351-6.
  • 15. Shin JK, Kim HC, Lee WY, Yun SH, Cho YB, Huh JW, et al. High preoperative serum CA 19-9 levels can predict poor oncologic outcomes in colorectal cancer patients on propensity score analysis. Annals of surgical treatment and research. 2019;96(3):107-15.
  • 16. Saito H, Kono Y, Murakami Y, Kuroda H, Matsunaga T, Fukumoto Y, et al. Influence of prognostic nutritional index and tumor markers on survival in gastric cancer surgery patients. Langenbeck's archives of surgery. 2017;402(3):501-7.
  • 17. Bodnar L, Wcislo GB, Smoter M, Gasowska-Bodnar A, Stec R, Synowiec A, et al. Cystatin C as a parameter of glomerular filtration rate in patients with ovarian cancer. Kidney and Blood Pressure Research. 2010;33(5):360-7.
  • 18. Strojan P, Budihna M, Šmid L, Svetic B, Vrhovec I, Kos J, et al. Prognostic significance of cysteine proteinases cathepsins B and L and their endogenous inhibitors stefins A and B in patients with squamous cell carcinoma of the head and neck. Clinical Cancer Research. 2000;6(3):1052-62.
  • 19. Kos J, Lah TT. Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer. Oncology reports. 1998;5(6):1349-410.
  • 20. Karcher D, McPherson R. Cerebrospinal, synovial, serous body fluids and alternative specimens. Henry’s clinical diagnosis and management by laboratory methods, 22th edition Richard A McPherson, Matthew R Pincus eds Elsevier Saunders, Philadelphia (PA). 2011:480-506.
  • 21. Herszényi L, Farinati F, Cardin R, István G, Molnár LD, Hritz I, et al. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer. BMC cancer. 2008;8(1):194.
  • 22. Štabuc B, Vrhovec L, Štabuc-Šilih M, Cizej TE. Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clinical chemistry. 2000;46(2):193-7.
  • 23. Kleber M, Cybulla M, Bauchmüller K, Ihorst G, Koch B, Engelhardt M. Monitoring of renal function in cancer patients: an ongoing challenge for clinical practice. Annals of oncology. 2007;18(5):950-8.
  • 24. Kos J, Krašovec M, Cimerman N, Nielsen HJ, Christensen IJ, Brünner N. Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis. Clinical Cancer Research. 2000;6(2):505-11.
  • 25. Grubb AO. Cystatin C-properties and use as diagnostic marker. Advances in clinical chemistry. 2001;35:63-99.
  • 26. Massey D. Commentary: clinical diagnostic use of cystatin C. Journal of clinical laboratory analysis. 2004;18(1):55-60.
  • 27. Kos J, Stabuc B, Schweiger A, Krasovec M, Cimerman N, Kopitar-Jerala N, et al. Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clinical cancer research. 1997;3(10):1815-22.
  • 28. Kos J, Werle B, Lah T, Brunner N. Cysteine proteinases and their inhibitors in extracellular fluids: markers for diagnosis and prognosis in cancer. The International journal of biological markers. 2000;15(1):84-9.
  • 29. Zore I, Krasovec M, Cimerman N, Kuhelj R, Werle B, Nielsen HJ, et al. Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer. Biological chemistry. 2001;382(5):805-10.
  • 30. Iacobuzio-Donahue CA, Shuja S, Cai J, Peng P, Murnane MJ. Elevations in cathepsin B protein content and enzyme activity occur independently of glycosylation during colorectal tumor progression. Journal of Biological Chemistry. 1997;272(46):29190-9.
There are 30 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Emiş Deniz Akbulut 0000-0003-1107-9650

Serpil Erdoğan 0000-0002-4234-8094

Serkan Akbulut 0000-0002-2043-2754

Fatma Meriç Yılmaz 0000-0002-8252-6975

Project Number Ankara Numune Eğitim ve Araştırma Hastanesi'nden 25/01/2012 tarih ve 2012-302 Karar no ile Etik Kurul onayı alınmıştır.
Publication Date December 25, 2020
Submission Date February 17, 2020
Acceptance Date November 9, 2020
Published in Issue Year 2020 Volume: 17 Issue: 3

Cite

Vancouver Akbulut ED, Erdoğan S, Akbulut S, Yılmaz FM. Mide ve Kolorektal Kanserli Hastalarda Serum Sistatin C Düzeyi ve CEA, CA 19-9 ile İlişkisinin İncelenmesi. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(3):372-7.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty