CA 19-9 AND ITS SIGNIFICANCE IN DIAGNOSIS AND SCREENING OF COLORECTAL CANCER
Keywords:
Са 19 9, Вevacizumab, vascular endothelial growth factor, colorectal cancerAbstract
The large intestine, as the final part of the digestive system, is a muscular-mucous organ, which is divided into: cecum, colon, and rectum. The digestion of food ends in it, assisted by intestinal juice containing alkaline mucin and beneficial microflora that participates in the synthesis of vitamins K, B12, B2, and B1. Feces are produced in the large intestine, which are then expelled from the body by the movement of the intestinal muscles. Colorectal cancer, as the most common cancer of the large intestine, develops from growths of the intestinal mucosa called polyps. Symptoms of colorectal cancer are most often bleeding, anemia, weight loss, changes in the rhythm of the stool. The most common causes of colorectal cancer are polyps, inflammatory bowel diseases, diabetes mellitus, excessive alcohol use, and reduced physical activity. The disease develops in several stages: from stage 0 when the intestinal mucosa is not affected to stage 4 when the cancer spreads into the muscular layer of the colon and metastasizes to other organs and the mucosa of the stomach wall. The tumor marker Ca 19-9 is the most commonly used marker when there is a suspicion that the patient suffers from colorectal cancer. It is not a tissue-specific marker and its concentration can also be increased in inflammatory processes of the colon, cirrhosis, hepatitis, Crohn's disease, ulcerative colitis, pancreatitis, gallstones. According to its chemical composition, it is a monoclonal antibody that also occurs in cancer of the colon, pancreas, stomach and bile ducts. Its synthesis requires the enzyme 1,4-fucosyl-transferase, which is not present in 5% of the world's population, in whom colorectal cancer may exist, but the concentration of Ca 19-9 should be within the reference limits of < 37 U/ml. Our goal was to prove the significance of determining the concentration of the tumor marker Ca 19-9 and therefore its concentration was measured in patients aged 50-75 years, divided into three groups: a control group of patients with a Ca 19-9 concentration within normal reference limits, a group diagnosed with colorectal cancer, and a group of patients undergoing anticancer therapy Bevacizumab. The method used to measure the level of Ca 19-9 concentration is an ELISA method that uses a solid-phase enzyme and is based on a sandwich system. The results obtained from the studies showed that patients diagnosed with Colorectal cancer have significantly higher results for the level of Ca 19-9 concentration compared to patients in the control group, while patients treated with therapy to reduce the level of Ca 19-9 in the blood, i.e. with Bevacizumab, have clearly reduced results for the level of Ca 19-9 to levels close to the control group, from which the effect of the treatment with Bevacizumab can be seen. The determination of Ca 19-9 is an auxiliary diagnosis in the diagnosis and treatment of colorectal cancer, and is not a primary diagnostic parameter of the disease. The diagnosis must be defined by histopathological analysis of the tumor, with increased values for Ca 19-9 together with a positive pathological finding confirming the diagnosis. When neoplastic polyp cells in the colon mucosa undergo mutations in the BRCA1 and BRCA2 genes and they lose their tumor suppressor function, the cells divide uncontrollably and form their own network of blood vessels, resulting in colorectal cancer. The drug Bevacizumab is an inhibitor of vascular endothelial growth factor, which prevents the formation of new blood vessels, resulting in tumor death. The effect of the use of anticancer therapy to reduce the level of Ca 19-9 in the serum, i.e. the inhibition of VEGF, and its binding to Bevacizumab, is visible, which prevents angiogenesis and thus tumor metastasis.
References
Aliseda, D., Arredondo, J., Sánchez-Justicia, C., Alvarellos, A, Rodríguez, J., Matos, I., Rotellar, F., Baixauli, J., Pastor, C. (2024). Survival and safety after neoadjuvant chemotherapy or upfront surgefor locally advanced colon cancer: meta-analysis. Br J Surg, 111(2):znae021. doi: 10.1093/bjs/znae021.
Boublikova, L., Novakova, A., Simsa, J., Lohynska, R. (2023). Total neoadjuvant therapy in rectal cancer: the
evidence and expectations. Crit Rev Oncol Hematol, 192:104196. doi: 10.1016/j.critrevonc.(2023).104196.
Backes, Y., Elias, SG., Groen, JN., Wolfhagen, W.H.J., Cercek, A.,Lumish, M., Sinopoli, J., Weiss, J., Shia, J.,
Lamendola-Essel, M., El Dika, H.I., Segal, N., Shcherba, M., Sugarman, R., Stadler, Z., Yaeger, R., Smith, J., Rousseau, B., Argiles, G. (2022). PD-1 Blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med, 386(25), 2363–76. doi: 10.1056/NEJMoa2201445.
Demir, N., Ozel, C., Avci, H., Dincer, M. (2021). Determination of therapeutic agents efficiencies of
microsatellite instability high colon cancer cells in post-metastatic liver biochip modeling. FASEB J, 35(9),e21834. doi: 10.1096/fj.202100333R. Chu, Q.D., Zhou, M.,
Ebata, Y., Nakanishi, R., Tanaka, Y., Tajiri, H., Zaitsu, Y., Nakashima, Y., Ota, M., Oki, E., Yoshizumi, T. (2024).
Neoadjuvant Chemotherapy in Patients With T4b or Obstructive Colon Cancer: A Single Center Retrospective Cohort Study. Anticancer Res, 44(3), 1281-1287. doi: 10.21873/anticanres.16923.
Gupta, K., Elfiky, A., Patel, E. (2023). Clinical Evidence for the Benefits of Neoadjuvant Chemotherapy and
Immunotherapy in Colon Cancer: A Concise Review. Discov Med, 35(179), 928-935. doi: 10.24976/Discov.Med.202335179.88.
Ludford, K., Ho, W.J., Thomas, J.V, Blum Murphy, M.B., Fleming, N.D., Lee, M.S., Smaglo, B.G., You, Y.N.,
Tillman, M.M., Kamiya-Matsuoka, C., Thirumurthi, S., Messick, C. (2023). Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors. J Clin Oncol, 41(12), 2181–2190. doi: 10.1200/JCO.22.01351.
Liu, S., Jiang, T., Xiao, L., Yang, S., Liu, Q., Gao, Y., Chen, G., Xiao, W. (2021). Total Neoadjuvant Therapy
(TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist, 26(9), e1555-e1566. doi: 10.1002/onco.13824.
Mestdagh, F., Steyaert, A., Lavand'homme, P. (2023). Cancer Pain Management: A Narrative Review of Current
Concepts, Strategies, and Techniques. Curr Oncol, 30(7), 6838-6858. doi: 10.3390/curroncol30070500.
Morton, D., Seymour, M., Magill, L., Glasbey, J., Glimelius, B., Palmer, A., Seligmann, J., Laurberg, S.,
Murakami, K., West, N., Quirke, P., Gray, R. (2023). Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol, 41(8), 1541-1552. doi: 10.1200/JCO.22.00046.
Nair, K.G., Kamath, S.D., Chowattukunnel, N., Krishnamurthi, S.S. (2024). Preoperative Strategies for Locally
Advanced Colon Cancer. Curr Treat Options Oncol, 25(3), 376- 388. doi: 10.1007/s11864-024-01184-6.
Patton, L., Avsar, P., Nugent, D.L., O'Connor, T., Patton, D., Moore, Z. (2021). What is the impact of specialist
palliative care outpatient consultations on pain in adult patients with cancer? A systematic review. Eur J Oncol Nurs, 55:102034. doi: 10.1016/j.ejon.2021.102034.
Popescu, I., Dudău, A.M., Dima, S., Herlea, V., Croitoru, V.M., Dinu, I.M., Miron, M., Lupescu, I., Croitoru-
Cazacu, I.M., Dumitru, R., Croitoru, A.E. (2024). Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review. Medicina (Kaunas), 60(5), 696. doi: 10.3390/medicina60050696.
Rathin, G., Clemente, C., Michel, M., Warrier, S.K., Kong, J.C. (2021). Neoadjuvant chemotherapy in locally
advanced colon cancer: a systematic review and metaanalysis. Int J Colorectal Dis, 36(10), 2063-2070. doi: 10.1007/s00384-021-03945-3.
Sugimoto, S., Arita, A., Shima, T., Takayama, S., Yamamoto, M., Okuda, J. (2023). A Case of Descending Colon
Cancer with Distant Metastasis That Was Controlled Severe Side Effects of Chemotherapy and Achieved Long-Term CR. Gan To Kagaku Ryoho, 50(13), 1906-1908. PMID: 38303248
Turri, G., Ostuzzi, G., Vita, G., Scarpa, A., Milella, M., Mazzarotto, R., Ruzzenente, A., Barbui, C., Pedrazzani,
C. (2024). Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta- 50 Analysis.C. JAMA Netw Open, 7(6), e2414702. doi: 10.1001/jamanetworkopen.2024.14702.
Tamburini, E., Tassinari, D., Ramundo, M., Viola M.G., Romano, C., Elia, M.T., Zanaletti, N., Rudnas, B.,
Casadei-Gardini, A., Delrio, P., Toma, I., Granata, V., Petrucelli, L., Avallone, A. (2022). Adjuvant chemotherapy after neoadjuvant chemo-radiotherapy and surgery in locally advanced rectal cancer. A systematic review of literature with a meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol, 172, 103627. doi: 10.1016/j.critrevonc.2022.103627.
Vendrely, V., Rivin Del Campo, E., Modesto, A., Jolnerowski, M., Meillan, N., Chiavassa, S., Serre, A., Gérard,
J.P., Créhanges, G., Huguet, F., Lemanski, C., Peiffert, D. (2022). Cancer Radiother, 26(12), 272-278. doi: 10.1016/j.canrad.202
