Enzymes are biological catalysts. More than this, enzymes can function as diagnostic tools. Therefore, this study explores various enzymes used as tumor markers.

1. LECTURER IN-CHARGE: DR (MRS) AYELAAGBE
THE USE OF ENZYMES AS TUMOR MARKERS
PRESENTED BY: BABALOLA, ISAAC OLAMIDE
TO THE DEPARTMENT OF MEDICAL
LABORATORY SCIENCES, LAUTECH

2. CANCER
• Cancer is a genetic disease caused by an uncontrolled
division of abnormal cells in the part of the body.
• It is often referred to as a Tumor
• Tumor means swelling of a part of the body, generally
without inflammation
• Also called Neoplasm, a new and abnormal growth of
tissue in some part of the body.
• Cancer can be Benign or Malignant
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3. TUMOR MARKERS
• Substances produced by the body in response to cancer
growth or by cancerous tissue itself.
• They are proteins, hormones, antigens, carbohydrates,
and enzymes.
• Tumor markers can be Cancer-specific markers
• Tumor markers can be Tissue-specific markers
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4. • According to their originated tissues cancers are classified as:
• Carcinoma Adenocarcinomas develop in organs and glands such as the prostate, liver, breast
cancer
• Squamous cell carcinomas develop in the epithelial such as the lung, skin, bladder
• Sarcomas developed from connective tissue (bone, ligament, tendon, fat
• Leukemia’s cancer of the blood that originates from bone marrow
CANCER CONT’D

5. Table 1.0: shows the statistics of prevalent cancer cases and cancer deaths
Cancer Cases Death
Breast 2.26 million 685,000
Lung 2.21 million 1.80 million
Colon and rectum 1.93 million 916,000
Prostate 1.41 million 375,000
Skin 1.20 million 57,000
Stomach 1.09 million 769,000
Liver 905,700 Thousand 830,000

6. CLASSIFICATION OF TUMOR
MARKERS
CANCER-SPECIFIC
MARKERS
• For screening the presence of cancer in
certain tissues.
• They are not specific for the diagnosis
• To determine disease progression
• Good for treatment monitoring
• Monitor cancer recurrence
• CEA, CA19-9, CA125
TISSUE-SPECIFIC MARKERS
• Related to specific tissue that
developed cancer
• Maybe be elevated in some other
related disease conditions of the
tissue.
• PSA, Thyroglobulin, AFP-L3, and
beta-hCG

7. Classification of tumor
markers according to
molecules
PROTEINS, HORMONES, AND
ENZYME MARKERS
Alpha-Feto protein
Beta-2 microglobulin
Calcitonin
Human Chorionic Gonadotropin(hCG)
Carcinoembryonic antigen (CEA)
Prostate-specific antigen (PSA)
Creatine kinase
Telomerase
Alkaline phosphatase (ALP)
CARBOHYDRATE MARKERS
Carbohydrate/Cancer antigen 15-3
Carbohydrate/Cancer antigen 125
Carbohydrate/Cancer antigen 19-9
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GENETIC MARKERS
Proto-oncogene: BCRA-1 and BCRA-2 causes
breast and ovarian cancer.
Tumor suppressor genes: P53, P21 and
Retinoblastoma gene

8. SOME OF THE
COMMONLY
ACCESSED TUMOR
MARKERS
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9. ASPARTATE AMINOTRANSFERASE (AST)
• Previously known as Serum Glutamate Oxaloacetate Transaminase (SGOT) but now has an EC
nomenclature of EC 2.6.1.1.
• Commonly found in the brain, kidneys, heart, and muscles but mostly found in the liver.
• Involved in transamination reaction between aspartate and glutamate that requires pyridoxal
phosphate as a cofactor. Important in amino acid metabolism and used as a biomarker of liver
health.
• Has two isoenzymes of cytosolic and mitochondrial forms. GOT1 or cAST- cytosolic isoenzyme
derived majorly from the RBCs and heart, and GOT2 or mAST- mitochondrial isoenzyme
peculiarly found in the liver.
• The isoenzymes evolved via gene duplication, sharing a sequence homology of approximately 45%
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10. AST CONT’D
• AST cal also serve as tumor markers
• Elevated level of AST can indicate Liver cancer
• Higher level of AST is significantly associated with an unfavorable prognosis in numerous cancer
such as hepatocellular and renal cell carcinoma as well as colonic, pancreatic, and breast cancer.
• Normal serum level: 8-20U/L. A range that is significantly elevated in liver diseases. Marked
increase is seen in Primary hepatoma (liver malignancy that results in cancer). A higher level
(>1000U/L) is seen in alcoholic hepatitis and liver injury.
• Other indications of elevated AST levels include: Chronic hepatitis, Cholestatis, and liver cirrhosis.
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11. ALKALINE PHOSPHATASE (ALP)
• Has an E.C nomenclature of EC 3.1.3.1
• Produced by osteoblast and localized in the cell membrane
• Normal Serum Level 40-150 U/L. May be increased in Children due Osteoblastic activities
• Moderate (2-3 times of the upper limit) increase is seen in infective hepatitis, alcoholic hepatitis,
and hepatocellular carcinoma.
• Very high (10-12 times of upper limit) increase may indicate extrahepatic obstruction (obstructive
jaundice) .
• Drastically high levels are seen in bone diseases e.g osteomalacia, and metastatic carcinoma.
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12. PROSTATE SPECIFIC ANTIGEN (PSA)
• Glycoprotein enzyme encoded by KLK3 gene in humans
• Specific for early screening and detection of prostate cancer.
• Tissue-specific tumor marker
• PSA is produced mainly by the prostate gland
• Serum PSA is the most sensitive tumor marker for monitoring individuals with prostate
cancer,
• including the progression of the disease and response to therapy
• In general, normal findings are 0 – 4.0 nanograms per milliliter (ng/ml).
• Optimal normal range is 0 – 2.6 ng/ml.
• May also be increased in Benign prostatic hyperplasia, prostatitis, and urinary tract
infections.
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13. LACTATE DEHYDROGENASE (LDH)
• It belongs to the oxidoreductase class and has an EC nomenclature of EC 1.1.1.27.
• Catalyses the reversible conversion of pyruvate to lactate with the reduction of NAD+ to
NADH in an anaerobic metabolic pathway. Serves as an important checkpoint in
gluconeogenesis and DNA metabolism.
• Hemolysis of RBCs increases LDH in circulation. Hence, producing false positive results.
Cellular necrosis can also result in increased serum concentration. There is also increased
LDH in malignancy as cancer cells predominantly undergo anaerobic glycolysis.
• Found in many tissues such as the muscles, heart, liver, kidney, pancreas, brain, and RBCs.
Serum percentage is capped at 10% and has slow electrophoretic mobility at pH 8.6
• Has a tetramer of 4 subunits that may either be H (heart) or M (muscle) polypeptide chains.
The chains have 5 different combinations producing 5 isoenzymes that are separated by
cellulose acetate electrophoresis.
• LDH-4 is the isoenzyme peculiar to the liver.
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14. LDH CONT’D
• Normal serum level: 100-200U/L. More concentrated in the RBC than in the serum.
• Increased LDH levels are seen in carcinomas, leukemia, and conditions that cause body cell
necrosis where a total LDH test is done.
• LDH-4 isoenzyme is measured to confirm a marked increase to determine a disorder in the liver.
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15. ALDOLASE
• Aldolase is a cytoplasmic enzyme involved in glucose and fructose metabolism
• Aldolase catalyzes the reversible reaction of converting fructose 1,6-bisphosphate into
dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate
• EC NUMBER 4.1.2.13;
• There are three subclasses of aldolase; A, B, and C.
• Aldolase A is expressed in muscles erythrocytes, and the brain;
• Aldolase B is expressed in the liver, kidneys, and enterocytes;
• Aldolase C is expressed in the brain.
• ALDOA is one of the most abundant glycolytic enzymes in tumor cells
• ALDOA promotes tumor growth and metastasis in hepatocellular carcinoma, cervical
adenocarcinoma, osteosarcoma, pancreatic cancer, lung cancer, and other tumors.
• Reference range : Adult: 3-8.2 Sibley-Lehninger units/dL or 22-59 mU/L at 37°C (SI units)
• Child: Approximately two times the adult values
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16. ALDOLASE CONT’D
• Newborn: Approximately four times the adult values
• Laboratory diagnosis:
• Aldolase is indirectly measured from a product using a substance that will react with the aldolase enzyme
within the collected sample.
• The measurement of the end product determines the level of aldolase contained in the patient’s serum.
A higher-than-normal level may be due to:
• Damage to skeletal muscles.
• Heart attack.
• Liver, pancreatic, or prostate cancer.
• Muscle diseases such as dermatomyositis, muscular dystrophy, and polymyositis.
• Swelling and inflammation of the liver (hepatitis)
• High aldolase expression was also related to colon cancer progression and metastasis
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17. 17
The application of the concept of tumor marker to
diagnose, detect as well as monitor tumor growth and
regression rely on the isolation and identification of
specific antigens. However, it is worth noting that in cases
where tumor-specific markers are used, tissue biopsy
should be done for confirmation.
CONCLUSION

18. Thank you for Listening