Tümör Biyobelirteçleri: Enzimler
Synopsis
In this review, the clinical significance and roles of enzymes in tumor diagnosis, treatment, prognosis, and recurrence monitoring are examined in detail. Since tumor cells possess a distinct protein and enzyme integrity compared to healthy tissues, enzymatic alterations serve as valuable disease-specific biomarkers. Key tumor-associated enzymes highlighted in the text include Prostate-Specific Antigen (PSA), used for screening, diagnosis, and follow-up in prostate carcinoma; Prostatic Acid Phosphatase (PAP), involved in metastatic prostate cancer diagnosis and immunotherapy targeting; and Lysozyme, elevated in acute myeloid and monocytic leukemias. Additionally, Neuron-Specific Enolase (NSE), utilized for staging and evaluating prognosis in small cell lung cancer and neuroblastoma, and Alkaline Phosphatase (ALP), which increases in primary or secondary liver tumors and bone metastases, are detailed. Furthermore, variations in tumor tissues of diverse enzymes—such as Matrix Metalloproteinases (MMPs) involved in tissue remodeling, the angiogenic protein Angiogenin, Thymidine Kinase as an important prognostic parameter in leukemia, CK-BB, Cyclin-Dependent Kinase 6, Caspase 3, and Pepsinogen 1 engaged in cell cycle and apoptosis processes, and Trypsin, whose activity decreases in hepatocellular carcinoma—are discussed. Consequently, while enzymatic biomarkers offer critical tools in cancer management, no single ideal biomarker exists due to relative limitations in sensitivity and specificity, highlighting the need for further research.
References
Wang M, Valenzuela L, Murphy G, et al. Purification of a human prostate specific antigen. Invest Urol, 1979; 17 (2), 159-163.
Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med, 1991; 324 (17), 1156-1161.
Stamey TA, Yang N, Hay AR, et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med, 1987; 317 (15), 909-916.
Taira A, Merrick G, Wallner K, et al. Reviving the acid phosphatase test for prostate cancer. Oncology (Williston Park), 2007; 21 (8), 1003-1010.
Babu GS, Supriya AN, Kumar NGR, et al. Tumor markers: An overview. J Orofac Sci, 2012; 4 (2), 87.
Malati T. Tumour markers: An overview. Indian J Clin Biochem, 2007; 22 (2), 17-31.
Afzal S, Ahmad M, Mushtaq S, et al. Morphological features correlation with serum tumour markers in prostatic carcinoma. J Coll Physicians Surg Pak, 2003; 13 (9), 511-514.
Potluri HK, Ng TL, Newton MA, et al. Antibody profiling of patients with prostate cancer reveals differences in antibody signatures among disease stages. J Immunother Cancer, 2020; 8 (2).
Keshav S, Chung P, Milon G, et al. Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization. J Exp Med, 1991; 174 (5), 1049-1058.
Osserman EF, Lawlor DP. Serum and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukemia. J Exp Med, 1966; 124 (5), 921-952.
Bancroft J, Marilyn G. (2002). Immunohistochemistry and diagnostic pathology. Theory and Practice of Histological Techniques. (5th edition) NY: Elsevier.
Shaikh NA, Memon F, Samro RP. Tumor Markers. T Pro Med J, 2014; 21 (04), 621-627.
Burtis CA, Bruns DE. (2014). Tietz fundamentals of clinical chemistry and molecular diagnostics. (7th edition) NY: Elsevier Health Sciences.
Neuschwander-Tetri BA. Common blood tests for liver disease. Which ones are most useful? Postgrad Med, 1995; 98 (1), 49-56.
Maldonado O, Demasi R, Maldonado Y, et al. Extremely high levels of alkaline phosphatase in hospitalized patients. J Clin Gastroenterol, 1998; 27 (4), 342-345.
Fishman WH, Inglis NI, Stolbach LL, et al. A serum alkaline phosphatase isoenzyme of human neoplastic cell origin. Cancer Res, 1968; 28 (1), 150-154.
Fishman WH, Inglis NR, Green S, et al. Immunology and biochemistry of Regan isoenzyme of alkaline phosphatase in human cancer. Nature, 1968; 219 (5155), 697-699.
Jung K, Lein M, Stephan C, et al. Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. Int J Cancer, 2004; 111 (5), 783-791.
Diamandis EP. (2002). Tumor markers: physiology, pathobiology, technology, and clinical applications. (1st edition) NY: Amer. Assoc. for Clinical Chemistry
Niewczas M, Paczek L, Krawczyk M, et al. Enzymatic activity of cathepsin B, cathepsin B and L, plasmin, trypsin and collagenase in hepatocellular carcinoma. Pol Arch Med Wewn, 2002; 108 (1), 653-662.
Peltonen R, Hagstrom J, Tervahartiala T, et al. High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases. Oncology, 2020; 1-17.
Kuropkat C, Plehn S, Herz U, et al. Tumor marker potential of serum matrix metalloproteinases in patients with head and neck cancer. Anticancer Res, 2002; 22 (4), 2221-2227.
Liutkevicius V, Lesauskaite V, Liutkeviciene R, et al. Matrix Metalloproteinases (MMP-2,-3,-9) Gene Polymorphisms in Cases of Benign Vocal Fold Lesions and Laryngeal Carcinoma. In Vivo, 2020; 34 (1), 267-274.
Pavlov N, Badet J. Angiogenin: involvement in angiogenesis and tumour growth. Bull Cancer, 2001; 88 (8), 725-732.
Lucas JJ, Domenico J, Gelfand EW. Cyclin-dependent kinase 6 inhibits proliferation of human mammary epithelial cells. Mol Cancer Res, 2004; 2 (2), 105-114.
Konturek SJ, Konturek PC, Bielanski W, et al. Serum progastrin and its products, gastric acid secretion and serum pepsinogen I in gastric cancer. Digestion, 2003; 68 (4), 169-177.
Akcay MN, Polat MF, Yilmaz I, et al. Serum paraoxonase levels in pancreatic cancer. Hepatogastroenterology, 2003; 50
Akcay MN, Yilmaz I, Polat MF, et al. Serum paraoxonase levels in gastric cancer. Hepatogastroenterology, 2003; 50
Soderberg A, Sahaf B, Rosen A. Thioredoxin reductase, a redox-active selenoprotein, is secreted by normal and neoplastic cells: presence in human plasma. Cancer Res, 2000; 60 (8), 2281-2289.
Hallek M, Wanders L, Ostwald M, et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma, 1996; 22 (5-6), 439-447.
Sun H, Zheng H, Yang X, et al. Expression of PTEN and Caspase-3 and their clinicopathological significance in primary gastric malignant lymphoma. Chin Med Sci J, 2004; 19 (1), 19-24.
Silverman LM, Dermer GB, Zweig MH, et al. Creatine kinase BB: a new tumor-associated marker. Clin Chem, 1979; 25 (8), 1432-1435.
