Early Detection of Digestive System Cancers: Insights from Enzymatic and Non-Enzymatic Tumour Markers

Biomarkers in Digestive System Cancer

Keywords: carcinoembryonic antigen, α-enolase, α-fetoprotein, calprotectin, colon cancer, rectum cancer, stomach cancer, digestive system cancer

Abstract


Background: Digestive system cancer is a silent yet dangerous disease and represents a major cause of death worldwide. Among these cancers, colon cancer is the second leading cause of cancer-related deaths globally. This study aimed to detect malignant cells at an early stage by analyzing biochemical indicators associated with the transformation of digestive cancer cells. Tumor markers, primarily proteins associated with malignant cells, may play a role in preventing the spread and progression of the disease.

Methods: In this study, the tumor markers analyzed included carcinoembryonic antigen (CEA), α-enolase (ENO1), α-fetoprotein (AFP), and calprotectin (CP) to detect digestive system cancer. These markers were measured in serum samples obtained from sixty patients with digestive system cancer (the patient group) and sixty healthy individuals (the control group).

Results: The results revealed highly significant changes (p-value < 0.00001) in the levels of CEA (56.698 ± 44.558 ng/mL), ENO1 (51.784 ± 10.395 ng/mL), AFP (116.275 ± 38.956 ng/mL), and CP (287.425 ± 33.181 ng/mL) in the cancerous group compared to the control group, suggesting their potential utility in early diagnosis. Furthermore, significant differences (p-value < 0.05) in liver enzymes and body mass index (BMI) provided additional evidence of pathological changes.

Conclusions: The biomarkers investigated in this study demonstrate promising potential for early diagnosis while contributing to a deeper understanding of the biological mechanisms underlying digestive system cancers. 

References

Jelski, W. andMroczko, B. (2020). Biochemical Markers of Colorectal Cancer - Present and Future. Cancer Manag Res, 12, 4789-4797. doi:10.2147/CMAR.S253369

Cueva, C., Gil-Sánchez, I., Ayuda-Durán, B., González-Manzano, S., González-Paramás, A.M., Santos-Buelga, C., Bartolomé, B., and Moreno-Arribas, M.V. (2017). An integrated view of the effects of wine polyphenols and their relevant metabolites on gut and host health. Molecules, 22(1), 99.

Harriss, D.J., Atkinson, G., George, K., Cable, N.T., Reilly, T., Haboubi, N., Zwahlen, M., Egger, M., Renehan, A.G., and group, C.C. (2009). Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index. Colorectal Dis, 11(6), 547-63. doi:10.1111/j.1463-1318.2009.01766.x

Espín, J.C., González-Sarrías, A., and Tomás-Barberán, F.A. (2017). The gut microbiota: A key factor in the therapeutic effects of (poly) phenols. Biochemical pharmacology, 139, 82-93.

Risan, T.Z. andAli, B.M. (2024). Study the effect of amphetamine on neurotransmitter factors in abusers individuals. Paper presented at the AIP Conference Proceedings.

Mileo, A.M., Nisticò, P., and Miccadei, S. (2019). Polyphenols: immunomodulatory and therapeutic implication in colorectal cancer. Frontiers in immunology, 10, 729.

Borzì, A.M., Biondi, A., Basile, F., Luca, S., Vicari, E.S.D., and Vacante, M. (2018). Olive oil effects on colorectal cancer. Nutrients, 11(1), 32.

Ali Numan, H., Almohanna, T., Q. Almayali, M., Adday Ali, R., Khazal Abdulghareeb Taha, H., and Addai Ali, H. (2024). The effect of Clusterin level as a potential marker in women with polycystic ovary syndrome. Edelweiss Applied Science and Technology, 8(5), 616-623. doi:10.55214/25768484.v8i5.1725

Swiderska, M., Choromanska, B., Dabrowska, E., Konarzewska-Duchnowska, E., Choromanska, K., Szczurko, G., Mysliwiec, P., Dadan, J., Ladny, J.R., and Zwierz, K. (2014). The diagnostics of colorectal cancer. Contemp Oncol (Pozn), 18(1), 1-6. doi:10.5114/wo.2013.39995

Cheng, Z., Shao, X., Xu, M., Zhou, C., and Wang, J. (2019). ENO1 Acts as a Prognostic Biomarker Candidate and Promotes Tumor Growth and Migration Ability Through the Regulation of Rab1A in Colorectal Cancer. Cancer Manag Res, 11, 9969-9978. doi:10.2147/CMAR.S226429

Jukic, A., Bakiri, L., Wagner, E.F., Tilg, H., and Adolph, T.E. (2021). Calprotectin: from biomarker to biological function. Gut, 70(10), 1978-1988.

Quentmeier, A., Möller, P., Schwarz, V., Abel, U., and Schlag, P. (1987). Carcinoembryonic antigen, CA 19‐9, and CA 125 in normal and carcinomatous human colorectal tissue. Cancer, 60(9), 2261-2266.

Gold, P. andFreedman, S.O. (1965). Specific carcinoembryonic antigens of the human digestive system. The Journal of experimental medicine, 122(3), 467-481.

Koness, R. (1995). CEA: is it of value in colorectal cancer? Rhode Island Medicine, 78(6), 164-166.

Zhu, X., Miao, X., Wu, Y., Li, C., Guo, Y., Liu, Y., Chen, Y., Lu, X., Wang, Y., and He, S. (2015). ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas. Exp Cell Res, 335(2), 216-23. doi:10.1016/j.yexcr.2015.05.020

Gao, J., Zhao, R., Xue, Y., Niu, Z., Cui, K., Yu, F., Zhang, B., and Li, S. (2013). Role of enolase-1 in response to hypoxia in breast cancer: exploring the mechanisms of action. Oncol Rep, 29(4), 1322-32. doi:10.3892/or.2013.2269

Tu, S.H., Chang, C.C., Chen, C.S., Tam, K.W., Wang, Y.J., Lee, C.H., Lin, H.W., Cheng, T.C., Huang, C.S., Chu, J.S., Shih, N.Y., Chen, L.C., Leu, S.J., Ho, Y.S., and Wu, C.H. (2010). Increased expression of enolase alpha in human breast cancer confers tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat, 121(3), 539-53. doi:10.1007/s10549-009-0492-0

Tsai, S.T., Chien, I.H., Shen, W.H., Kuo, Y.Z., Jin, Y.T., Wong, T.Y., Hsiao, J.R., Wang, H.P., Shih, N.Y., and Wu, L.W. (2010). ENO1, a potential prognostic head and neck cancer marker, promotes transformation partly via chemokine CCL20 induction. Eur J Cancer, 46(9), 1712-23. doi:10.1016/j.ejca.2010.03.018

Duijvesz, D., Burnum-Johnson, K.E., Gritsenko, M.A., Hoogland, A.M., Vredenbregt-van den Berg, M.S., Willemsen, R., Luider, T., Pasa-Tolic, L., and Jenster, G. (2013). Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer. PLoS One, 8(12), e82589. doi:10.1371/journal.pone.0082589

Bai, Z., Ye, Y., Liang, B., Xu, F., Zhang, H., Zhang, Y., Peng, J., Shen, D., Cui, Z., Zhang, Z., and Wang, S. (2011). Proteomics-based identification of a group of apoptosis-related proteins and biomarkers in gastric cancer. Int J Oncol, 38(2), 375-83. doi:10.3892/ijo.2010.873

Stříž, I. andTrebichavský, I. (2004). Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiol Res, 53, 245-253.

Savaş, O. andİpek, V. (2021). Investigation of Calprotectin positive leukocytes in canine soft tissue tumors. Journal of Research in Veterinary Medicine, 40(2), 77-87.

Shiojima, Y., Moriyama, H., Takahashi, M., Takahashi, R., Maruyama, K., Bagchi, M., and Bagchi, D. (2022). Novel ELISA technology in assessing undenatured type II collagen in functional foods and dietary supplements used for knee joint health care: its sensitivity, precision, and accuracy. Functional Foods in Health and Disease, 12(5), 234. doi:10.31989/ffhd.v12i5.933

Almohanna, T., Ahmed, S.A., and Hussain, M.K. (2012). Relevance of sex hormones levels with spermogram of infertile men. Global J Med Res2012, 12, 15-18.

Rifai, N. (2023). Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics-E-Book: Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics-E-Book: Elsevier Health Sciences.

Auda, F.M., Ali, A.M., and Dhyaa, S. (2021). Levels of Heavy Metal and Trace Element among Children with Autism Spectrum Disorders. Paper presented at the Journal of Physics: Conference Series.

Rathore, G.S. (2023). Biostatistics And Research Methodology: Academic Guru Publishing House.

Hsiao, K.-C., Shih, N.-Y., Fang, H.-L., Huang, T.-S., Kuo, C.-C., Chu, P.-Y., Hung, Y.-M., Chou, S.-W., Yang, Y.-Y., and Chang, G.-C. (2013). Surface α-enolase promotes extracellular matrix degradation and tumor metastasis and represents a new therapeutic target. PloS one, 8(7), e69354.

Johnson, P.J. (2001). The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clinics in liver disease, 5(1), 145-159.

Goldstein, M.J. andMitchell, E.P. (2005). Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer investigation, 23(4), 338-351.

Duffy, M.J. (2001). Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clinical chemistry, 47(4), 624-630.

Dooley, J.S., Lok, A.S., Garcia-Tsao, G., and Pinzani, M. (2018). Sherlock's diseases of the liver and biliary system: John Wiley & Sons.

Giannini, E.G., Testa, R., and Savarino, V. (2005). Liver enzyme alteration: a guide for clinicians. Cmaj, 172(3), 367-379.

Ali, B. and Mohammed, U.J. (2024). The association of atherosclerosis with cortisol and alpha-enolase levels and lipid profile. Anaesthesia, Pain & Intensive Care, 28(6), 1097-1104.

Rehman, A. andAuda, F.M. (2025). Evaluation of midkine, cortisol, and other biochemical indicators in patients with atherosclerosis. Anaesthesia, Pain & Intensive Care, 29(1), 40-46.

Shokrgozar, M.A., Zali, H., Rezaei-Tavirani, M., and Moghadamnia, S. (2007). Evaluation of proliferation inhibition effect of human calprotectin on human gastric cancer cell line (AGS) in vitro. Cell Journal (Yakhteh), 8(4), 258-263.

Ross, F.A., Park, J.H., Mansouri, D., Combet, E., Horgan, P.G., McMillan, D.C., and Roxburgh, C.S.D. (2022). The role of faecal calprotectin in diagnosis and staging of colorectal neoplasia: a systematic review and meta-analysis. BMC Gastroenterol, 22(1), 176. doi:10.1186/s12876-022-02220-1

Díaz-Ramos, À., Roig-Borrellas, A., García-Melero, A., and López-Alemany, R. (2012). α‐enolase, a multifunctional protein: its role on pathophysiological situations. BioMed Research International, 2012(1), 156795.

Song, Y., Luo, Q., Long, H., Hu, Z., Que, T., Zhang, X.a., Li, Z., Wang, G., Yi, L., and Liu, Z. (2014). Alpha-enolase as a potential cancer prognostic marker promotes cell growth, migration, and invasion in glioma. Molecular cancer, 13, 1-12.

Vander Heiden, M.G., Cantley, L.C., and Thompson, C.B. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. science, 324(5930), 1029-1033.

Yang, J., Zhou, M., Zhao, R., Peng, S., Luo, Z., Li, X., Cao, L., Tang, K., Ma, J., Xiong, W., Fan, S., Schmitt, D.C., Tan, M., Li, X., and Li, G. (2014). Identification of candidate biomarkers for the early detection of nasopharyngeal carcinoma by quantitative proteomic analysis. J Proteomics, 109, 162-75. doi:10.1016/j.jprot.2014.06.025

Zhan, P., Zhao, S., Yan, H., Yin, C., Xiao, Y., Wang, Y., Ni, R., Chen, W., Wei, G., and Zhang, P. (2017). α‐enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer. Molecular carcinogenesis, 56(5), 1427-1437.

Thomas, J.D., Zhang, Y.-J., Wei, Y.-H., Cho, J.-H., Morris, L.E., Wang, H.-Y., and Zheng, X.S. (2014). Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer cell, 26(5), 754-769.

Almohanna, T. and Al-Aadily, I. (2021). RNA Editing with CRISPR Cas13. Academia Letters, 2. doi:10.20935/al1129.

Published
2025/04/02
Section
Original paper