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Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer.
- Source :
-
Cancer [Cancer] 2013 Feb 01; Vol. 119 (3), pp. 575-85. Date of Electronic Publication: 2012 Aug 01. - Publication Year :
- 2013
-
Abstract
- Background: The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC.<br />Methods: Plasma and bile M2-PK concentrations were measured by enzyme-linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing techniques.<br />Results: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas silencing in an M2-PK-positive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PK-transfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation.<br />Conclusions: Bile M2-PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA-mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target.<br /> (Copyright © 2012 American Cancer Society.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Bile chemistry
Bile metabolism
Biliary Tract Neoplasms genetics
Biliary Tract Neoplasms mortality
Biliary Tract Neoplasms pathology
Carcinoma genetics
Carcinoma mortality
Carcinoma pathology
Case-Control Studies
Cell Line, Tumor
Disease Progression
Female
Humans
Male
Middle Aged
Prognosis
Pyruvate Kinase blood
Pyruvate Kinase genetics
Pyruvate Kinase metabolism
Survival Analysis
Biliary Tract Neoplasms diagnosis
Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Biomarkers, Tumor physiology
Carcinoma diagnosis
Pyruvate Kinase physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 119
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 22864959
- Full Text :
- https://doi.org/10.1002/cncr.27611