Cathepsin D as a Biomarker in Colon Cancer Patients

Download Article

DOI: 10.21522/TIJPH.2013.13.01.Art090

Authors : Rafad R. S. Mohammed, Mujda A. M. Murad

Abstract:

Colon cancer is a relatively common life-threatening malignancy for both sexes. Cancer cells are depicted by the upregulation of lysosomal proteases – cathepsin D. The study aimed to determine human cathepsin D activity in the control group as well as its role in metastasis and invasion of colon cancer. Enzymatic assay(manual) was used to measure the activity of cathepsin D and catalase, other parameters were measured using analytical kits provided by reputable companies. Carcinoembryonic antigen CEA has been determined as a biomarker for colon cancer, patients were subdivided into two classes based on carcinoembryonic antigen values: group 1, ≤5 ng/mL group 2 >5 ng/mL. The results explained that the normal value of Cathepsin D for the control group was (8.61±0.294 ngml) and the activity of the enzyme was not affected by gender, age, smoking and BMI. The results also proved a highly significant increase in cathepsin D activity in the patient's group (17.81±0. 652 ng/ml) compared to the control. A remarkable elevation in the action of cathepsin D in colon cancer patients was associated with a positive relationship with carcinoembryonic antigen levels. This supports the application of cathepsin D as a marker of tumor occurrence as well as evidence of tumor metastasis and invasion after treatment in colon cancer patients.


References:

[1].   Merkhan, M. M., Faisal, I. M., Alsaleem, D. Z., Shindala, O. M., Almukhtar, H. M., Thanoon, I. A., 2020, Immunodepressant and oxidant potential of standard leukaemia drug regimen. International Journal of Research in Pharmaceutical Sciences, 11(4), 1-4.

[2].   Patel, S., Homaei, A., El-Seedi, H. R., Akhtar, N., 2018, Cathepsins: Proteases that are vital for survival but can also be fatal. Biomedicine & Pharmacotherapy, 105, 526-532.

[3].   Rawlings, N. D., Barrett, A. J., Finn, R., 2016, Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic acids research, 44(D1), D343-D350.

[4].   Metcalf, P., Fusek, M., 1993, Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. The EMBO Journal, 12(4), 1293-1302.‏

[5].   Chen, S., Dong, H., Yang, S., Guo, H., 2017, Cathepsins in digestive cancers. Oncotarget, 8(25), 41690.

[6].   Benes, P., Vetvicka, V., Fusek, M., 2008, Cathepsin D—many functions of one aspartic protease. Critical reviews in oncology/hematology, 68(1), 12-28.

[7].   Pranjol, M. Z. I., Gutowski, N. J., Hannemann, M., Whatmore, J. L., 2018, Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1865(1), 25-33.

[8].   Buck, M. R., Karustis, D. G., Day, N. A., Honn, K. V., Sloane, B. F., 1992, Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochemical Journal, 282(1), 273-278.

[9].   Yoshinari, M., Taurog, A., 1985, Lysosomal digestion of thyroglobulin: role of cathepsin D and thiol proteases. Endocrinology, 117(4), 1621-1631.

[10].  Seo, S. U., Woo, S. M., Im, S. S., Jang, Y., Han, E., Kim, S. H., Kwon, T. K., 2022, Cathepsin D as a potential therapeutic target to enhance anticancer drug-induced apoptosis via RNF183-mediated destabilization of Bcl-xL in cancer cells. Cell Death & Disease, 13(2), 115.

[11].  Office for National Statistics: Mortality Statistics-Deaths registered in England and Wales Published online. 2014. [Available at: http://www.ons.gov.uk/ons/publications/allreleases.html?definition=tcm%3A77-27475

[12].  WHO. Leading cause of death in Europe: fact sheet Copenhagen: WHO Regional Office for Europe; 2012 [Available at: https://data.euro.who.int/hfadb]

[13].  Mohammadpour, A. H., Salehinejad, Z., Elyasi, S., Mouhebati, M., Mirhafez, S. R., Samadi, S., Sahebkar, A., 2018, Evaluation of serum cathepsin D concentrations in coronary artery disease. Indian Heart Journal, 70(4), 471-475.

[14].  Botteri, E., Iodice, S., Bagnardi, V., Raimondi, S., Lowenfels, A. B., Maisonneuve, P., 2008, Smoking and colorectal cancer: a meta-analysis. Jama, 300(23), 2765-2778.

[15].  Liang, P. S., Chen, T. Y., Giovannucci, E., 2009, Cigarette smoking and colorectal cancer incidence and mortality: Systematic review and meta‐analysis. International Journal of cancer, 124(10), 2406-2415.

[16].  Meester, R. G., Mannalithara, A., Lansdorp-Vogelaar, I., Ladabaum, U., 2019, Trends in incidence and stage at diagnosis of colorectal cancer in adults aged 40 through 49 years, 1975-2015. Jama, 321(19), 1933-1934.

[17].  Burkitt, D. P., 1971, Epidemiology of cancer of the colon and rectum. Cancer, 28(1), 3-13.

[18].  Giovannucci, E., 2002, Modifiable risk factors for colon cancer. Gastroenterology Clinics, 31(4), 925-943.

[19].  Hastuti, S., 2024, Breast Cancer Screening Access Among Low-Income Women Under Social Health Insurance: A Scoping Review. Public Health of Indonesia, 10(1), 21-32.

[20].  Thoke, G. M., PP, A. S. U., Ganapathy, D., Sekar, D., 2024, Analysis of TGF-β Gene Expression in Carboplatin Treated Lung Cancer Cells. exila International Journal of Public Health, 12(3).

[21].  Kumar, R. S., Amudha, P., Vidya, R., Kalpana, C. S., Sudhashini, S., 2024, A Review on Anticancer Properties of Chebulagic Acid from Terminalia chebula. Texila International Journal of Public Health, 12(3).‏

[22].  Eshrati Yeganeh, F., Tabarzad, M., Khazraei, H., Bourbour, M., 2023, Synthesis and evaluation of Escitalopram-loaded niosomes on colon cancer cell lines. Physiology and Pharmacology, 27(3), 307-318.‏

[23].  Hariani, H., Wiralis, W., Faturrahman, T. F. T., Suwarni, S., 2025, Medium Time Heating of Syrop from Red Betel Leaf (Piper crocatum ruiz pav) Can Reduce Carcinoembryonic Antigen (CEA) Level Among Adult Women in Southeast Sulawesi, Indonesia. Public Health of Indonesia, 11(S1), 80-88.

[24].  Oliveira, C. S. F., Pereira, H., Alves, S., Castro, L., Baltazar, F., Chaves, S. R., Côrte-Real, M., 2015, Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria. Cell Death & Disease, 6(6), e1788-e1788.

[25].  Mijanovic, O., Petushkova, A. I., Brankovic, A., Turk, B., Solovieva, A B., Nikitkina, A. I., Zamyatnin Jr, A. A., 2021, Cathepsin D—managing the delicate balance. Pharmaceutics, 13(6), 837.

[26].  Skrzydlewska, E., Sulkowska, M., Wincewicz, A., Koda, M., Sulkowski, S., 2005, Evaluation of serum cathepsin B and D in relation to clinicopathological staging of colorectal cancer. World Journal of Gastroenterology: WJG, 11(27), 4225.

[27].  Piecuch, A., Kurek, J., Kucharzewski, M., Wyrobiec, G., Jasiński, D., Brzozowa-Zasada, M., 2020, Catalase immunoexpression in colorectal lesions. Gastroenterology Review/Przegląd Gastroenterologiczny, 15(4), 330-337.

[28].  Hong, S. W., Lee, H. J., Han, K., Moon, J. M., Park, S., Soh, H., Kim, J. S., 2021, Risk of gastrointestinal cancer in patients with an elevated level of gamma-glutamyltransferase: A nationwide population-based study, PloS One, 16(2), e0245052.

[29].  Abdul‐Wahid, A., Cydzik, M., Fischer, N. W., Prodeus, A., Shively, J. E., Martel, A., Gariépy, J., 2018, S erum‐derived carcinoembryonic antigen (CEA) activates fibroblasts to induce a local re‐modeling of the extracellular matrix that favors the engraftment of CEA‐expressing tumor cells. International Journal of Cancer, 143(8), 1963-1977.

[30].  Digala1, P., Muthu, S., Subramani, N., Duraisamy, N., Sundararaj, D., 2024, Understand the Fatty Acid Metabolic Reprogramming of Immune Cells in Colorectal Cancer. Texila International Journal of Public Health, 12(3): 1-8.