Transglutaminase 3 expression in hepatocellular carcinoma patients: Correlation with tumor features and survival profile |
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| Affiliation: | 1. Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;2. Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China;1. Department of Clinical Medicine, The First Clinical Medical College of Lanzhou University, Lanzhou, China;2. Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China;3. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China;4. Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors of Gansu Province, Lanzhou, China;5. Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China;1. Paris University; Siric CARPEM, Assistance Publique - Hôpitaux de Paris, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France;2. Paris University; Assistance Publique - Hôpitaux de Paris, Pathology Department, Hôpital Européen GeorgesPompidou, Paris, France;3. Paris University; Assistance Publique - Hôpitaux de Paris, Dermatology Department, Hôpital Beaujon, Clichy, France;1. MRI Department, the First Affiliated Hospital of Henan University of Chinese Medicine, No 19 Renmin Road, Zhengzhou, Henan, China;2. Department of Radiology, Gold Coast University Hospital, Queensland, Australia;1. Department of Digestive and Surgical Oncology, University Hospital, Dijon, France;2. Digestive Cancer Registry of Burgundy, Dijon, France;3. Department of Medical Oncology, Georges-Francois Leclerc Centre, Dijon, France;4. Department of Geriatrics and Internal Medicine, University Hospital, Dijon, France;5. Department of Digestive and Surgical Oncology, University Hospital, Dijon, France;1. Registre des tumeurs, Parc Euromedecine, 208 rue des Apothicaires 34298 Montpellier, France;2. Research Unit INSERM University of Montpellier, IDESP Institute Desbrest of Epidemiology and Public Health, Montpellier, France;3. Department of Digestive surgery, CHU Carémeau, Place du Pr Debré, 30 090 Nîmes, France;1. Sorbonne Université, INSERM, Centre de recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), F-75012 Paris, France;2. AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Service d''Hépato-Gastroentérologie, Unité de Soins Intensifs d''Hépatologie, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, F-75013 Paris, France;3. AP-HP.Sorbonne Université, Hôpital Saint-Antoine, Service d''Anatomo-Pathologie, Service d''Hépatologie, Centre de Référence Maladie Rare (CRMR) Maladies Inflammatoires des Voies Biliaires-Hépatites Auto-immunes (MIVB-H), Service de Biochimie, F-75012 Paris, France;4. INSERM U 1016, Institut Cochin, Paris, France;5. AP-HP.Sorbonne Université, Hôpital Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE), F-75013 Paris, France |
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| Abstract: | BackgroundTransglutaminase 3 (TGM3) regulates multiple oncogene pathways (GSK-3β/β-catenin pathway, Akt/ERK pathway, etc.) to promote hepatocellular carcinoma (HCC) cell proliferation, migration and invasion, however, its clinical value for HCC management is still limited. Therefore, we conducted this study to compare the TGM3 expression between tumor tissue and paired adjacent noncancerous tissue, aiming to explore the clinical application of TGM3 in HCC patients.MethodsTotally, 208 HCC patients were enrolled and their clinicopathological features were collected. Then, 208 pairs of HCC specimens and adjacent noncancerous specimens were used to detect TGM3 protein expression by IHC assay and assessed by a semi-quantitative scoring method. Besides, 157 pairs were proposed to detect TGM3 mRNA expression by RT-qPCR.ResultsBoth TGM3 protein (P<0.001) and mRNA (P<0.001) levels were increased in HCC specimens compared to adjacent noncancerous specimens. Besides, TGM3 high protein expression correlated with multifocal tumor nodules (P<0.001), advanced Barcelona Clinic Liver Cancer (BCLC) stage (P = 0.006), higher carcinoembryonic antigen (P = 0.038) and alpha-fetoprotein (AFP) (P<0.001). While TGM3 high mRNA expression correlated with multifocal tumor nodules (P = 0.025), largest tumor size ≥ 5.0 cm (P = 0.042) and higher AFP (P = 0.019). Furthermore, both TGM3 protein (P = 0.002) and mRNA (P = 0.028) high expressions correlated with shorter overall survival (OS). While after adjustment by multivariant Cox's regression, TGM3 protein high expression (vs. low) independently predicted worse OS (P = 0.004).ConclusionsTMG3 expression is increased in tumor tissue, also its high expression correlates with multiple tumor nodules, higher BCLC stage, abnormal AFP and reduced OS in HCC patients. |
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