Sureerat Padthaisong1, Malinee Thanee2,3, Nisana Namwat1,2,3, Jutarop Phetcharaburanin1,2,3, Poramate Klanrit1,2,3, Narong Khuntikeo2,3,4, Attapol Titapun2,3,4, Watcharin Loilome5,6,7. 1. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mittraparp Road, Muang District, Khon Kaen, 40002, Thailand. 2. Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, 40002, Thailand. 3. Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. 4. Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. 5. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mittraparp Road, Muang District, Khon Kaen, 40002, Thailand. watclo@kku.ac.th. 6. Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, 40002, Thailand. watclo@kku.ac.th. 7. Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. watclo@kku.ac.th.
Abstract
BACKGROUND: Cancer recurrence is one of the most concerning clinical problems of cholangiocarcinoma (CCA) patients after treatment. However, an identification of predictive factor on Opisthorchis viverrini (OV)-associated CCA recurrence is not well elucidated. In the present study, we aimed to investigate the correlation of twelve targeted protein kinases with CCA recurrence. METHODS: Twelve protein kinases, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, 3, 4 (HER2, HER3, HER4), vascular endothelial growth factor receptor 3 (VEGFR3), vascular endothelial growth factor-C (VEGF-C), erythropoietin-producing hepatocellular carcinoma receptor type-A3 (EphA3), EphrinA1, phosphor-serine/threonine kinase 1 (p-Akt1), serine/threonine kinase 1 (Akt1), beta-catenin and protein Wnt5a (Wnt5a) were examined using immunohistochemistry. Pre-operative serum tumor markers, CA19-9 and CEA were also investigated. RESULTS: Among twelve protein kinases, EGFR, HER4, and EphA3 were associated with tumor recurrence status, recurrence-free survival (RFS) and overall survival (OS). Multivariate cox regression demonstrated that EGFR, HER4, EphA3 or the panel of high expression of these proteins was an independent prognostic factor for tumor recurrence. The combination of high expression of these proteins with a high level of CA19-9 could improve the predictive ability on tumor recurrence. Moreover, the patients were stratified more accurately when analyzed using the combination of high expression of these proteins with primary tumor (T) or lymph node metastasis (N) status. CONCLUSION: EGFR, HER4, EphA3 or the panel of high expression of these proteins is an independent prognostic factor for post-operative CCA recurrence.
BACKGROUND:Cancer recurrence is one of the most concerning clinical problems of cholangiocarcinoma (CCA) patients after treatment. However, an identification of predictive factor on Opisthorchis viverrini (OV)-associated CCA recurrence is not well elucidated. In the present study, we aimed to investigate the correlation of twelve targeted protein kinases with CCA recurrence. METHODS: Twelve protein kinases, epidermal growth factor receptor (EGFR), humanepidermal growth factor receptor 2, 3, 4 (HER2, HER3, HER4), vascular endothelial growth factor receptor 3 (VEGFR3), vascular endothelial growth factor-C (VEGF-C), erythropoietin-producing hepatocellular carcinoma receptor type-A3 (EphA3), EphrinA1, phosphor-serine/threonine kinase 1 (p-Akt1), serine/threonine kinase 1 (Akt1), beta-catenin and protein Wnt5a (Wnt5a) were examined using immunohistochemistry. Pre-operative serum tumor markers, CA19-9 and CEA were also investigated. RESULTS: Among twelve protein kinases, EGFR, HER4, and EphA3 were associated with tumor recurrence status, recurrence-free survival (RFS) and overall survival (OS). Multivariate cox regression demonstrated that EGFR, HER4, EphA3 or the panel of high expression of these proteins was an independent prognostic factor for tumor recurrence. The combination of high expression of these proteins with a high level of CA19-9 could improve the predictive ability on tumor recurrence. Moreover, the patients were stratified more accurately when analyzed using the combination of high expression of these proteins with primary tumor (T) or lymph node metastasis (N) status. CONCLUSION:EGFR, HER4, EphA3 or the panel of high expression of these proteins is an independent prognostic factor for post-operative CCA recurrence.
Entities:
Keywords:
Cancer recurrence; Cholangiocarcinoma; Prognostic factor; Protein kinase; Tumor marker