OBJECTIVETo evaluate the clinical significance of blood and fecal expression of tumor M2-pyruvate kinase (Tumor M2-PK) in patients with colorectal cancer.

METHODSWith 22 healthy subjects as controls, 44 patients with CRC were examined for tumor M2-PK in serum and fecal samples using a sandwich enzyme immunoassay.

RESULTSThe sensitivity of serum and fecal tumor M2-PK for detecting CRC was 59.1% and 63.6% with a specificity of 86.4% and 81.8%, respectively. The serum and fecal levels of tumor M2-PK showed a significant correlation in CRC patients.

CONCLUSIONTumor M2-PK has good sensitivity and specificity in the diagnosis of CRC.

Biomarkers, Tumor ; metabolism ; Case-Control Studies ; Colorectal Neoplasms ; blood ; metabolism ; Feces ; enzymology ; Female ; Humans ; Male ; Pyruvate Kinase ; blood ; metabolism

BACKGROUND/AIMS: Pyruvate kinase (PK) is a key enzyme of glycolysis. Different isoforms of this enzyme are tissue-specifically expressed (M2-PK, M1-PK, R-PK, L-PK). The concentration of the dimeric M2-PK is increased in a metabolic state of tumor cells. In this case, the dimeric M2-PK is termed Tumor M2-PK. We investigated EDTA-plasma of 73 patients with gastrointestinal (GI) cancer and 61 healthy controls to evaluate its significance in diagnosing GI cancer. METHODS: Plasma Tumor M2-PK was measured using an ELISA assay based on two monoclonal antibodies which specifically react with the dimeric Tumor M2-PK. RESULTS: The sensitivity of Tumor M2-PK was 67.1% for all GI cancers, that of CA 19-9 was 38.4% and that of CEA was 34.3%. The specificity of Tumor M2-PK was 91.8% (cutoff=20 U/mL). Tumor M2-PK showed a high sensitivity in gastric cancer (62.2%), colorectal cancer (66.7%) and bile duct cancer (75.0%). In colorectal cancer, the combination of Tumor M2-PK with CEA resulted in a remarkable increase in the sensitivity (86.2%). The average Tumor M2-PK levels were generally elevated in the metastatic GI cancer patients compared to nonmetastatic patients, especially in stomach cancer with statistical significance (p=0.005). CONCLUSIONS: Tumor M2-PK in EDTA-plasma seems to be a new valuable tumor marker in GI cancer.
Adult ; Aged ; Digestive System Neoplasms/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Gastrointestinal Neoplasms/diagnosis ; Humans ; Male ; Middle Aged ; Pyruvate Kinase/*blood ; Sensitivity and Specificity ; Tumor Markers, Biological/*blood

A kinetic assay for total calcium in serum was developed which is based on the activation of Ca++-ATPase by free Ca++ [Ca++]f maintained by EGTA in the reaction mixture. The concentration of Caf++ was dependent on total reference calcium added or serum calcium. Ca++-ATPase activity was coupled to the reduction of NADH by pyruvate kinase (PK) and lactate dehydrogenase (LDH) and monitored by change in absorbance at 340 nm. The calcium in normal serum was 10.08 +/- 0.24 mg/ dl (n = 35) by our method while with o-cresolphthalein complexone (CPC) method, the total calcium in the same 35 serum samples was 10.14 +/- 0.54 mg/dl. The range of within-run coefficient of variations (CVs) by this method was 0.9-2.87% at 8-12 mg/dl and day-to-day CVs were 0.72-3.17%. The presence of other ions and standard clinical interfering agents did not affect this assay system. The correlation between values obtained with our method (y) and CPC method (x) for normal serum was: y = 1.064x-0.580 mg/dl (r = 0.912, n = 59).
Adenosinetriphosphatase/metabolism ; Adolescent ; Adult ; Calcium/*blood ; Comparative Study ; Enzyme Activation ; Female ; Human ; Kinetics ; Male ; NAD/metabolism ; Pyruvate Kinase/metabolism ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity

BACKGROUND/AIMS: M2 pyruvate kinase (M2-PK) is an enzyme that is produced in undifferentiated and proliferating tissues. This study aims to evaluate the usefulness of the immunochromatographic M2 pyruvate kinase (iM2-PK) for the screening of colorectal cancer (CRC) and premalignant lesions. METHODS: Healthy volunteers and patients with colorectal neoplasia were enrolled in six academic hospitals in the capital province of Korea. The iM2-PK value was compared with the immunochromatographic fecal occult blood test (iFOBT) and fecal tumor M2-PK enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 323 subjects were enrolled. The sensitivity of iM2-PK for CRC was 92.8%, which was superior to iFOBT (47.5%, p<0.0001). For adenomatous lesions, the sensitivity of iM2-PK was 69.4%, which was also superior to iFOBT (12.1%, p<0.001). Compared with M2-PK ELISA, iM2-PK exhibited significantly enhanced sensitivity for CRC (97.5% vs 80.0%, p=0.0289). The sensitivity of iM2-PK was higher in advanced stages of CRC compared with cancers confined to the mucosa and submucosa (p<0.05). However, lymph node metastasis had no influence on the sensitivity of iM2-PK. CONCLUSIONS: The iM2-PK exhibited increased sensitivity for identifying CRC and adenomatous lesions compared with iFOBT. Given its rapid results and convenience, CRC screening using iM2-PK is promising.
Adenoma/*diagnosis ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Clinical Enzyme Tests/*instrumentation ; Colorectal Neoplasms/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Feces/*enzymology ; Female ; Healthy Volunteers ; Humans ; Immunochromatography/methods ; Male ; Middle Aged ; Occult Blood ; Precancerous Conditions/diagnosis/enzymology ; Predictive Value of Tests ; Pyruvate Kinase/*analysis ; Reagent Kits, Diagnostic ; Republic of Korea ; Sensitivity and Specificity