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Sun J, Xia Y, Shen F, Cheng S. Chinese expert consensus on the diagnosis and treatment of hepatocellular carcinoma with microvascular invasion (2024 edition). Hepatobiliary Surg Nutr 2025; 14:246-266. [PMID: 40342785 PMCID: PMC12057508 DOI: 10.21037/hbsn-24-359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/10/2024] [Indexed: 05/11/2025]
Abstract
Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Surgical resection is the preferred treatment for HCC, but the postoperative recurrence and metastasis rates are high. Current evidence shows that microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis, but there are still many controversies about the diagnosis, classification, prediction, and treatment of MVI worldwide. Methods Systematic literature reviews to identify knowledge gaps and support consensus statements and a modified Delphi method to develop evidence- and expert-based guidelines and finalization of the clinical consensus statements based on recommendations from a panel of experts. Results After many discussions and revisions, the Chinese Association of Liver Cancer of the Chinese Medical Doctor Association organized domestic experts in related fields to form the "Chinese expert consensus on the diagnosis and treatment of hepatocellular carcinoma with microvascular invasion (2024 edition)" which included eight recommendations to better guide the prediction, diagnosis and treatment of HCC patients with MVI. The MVI pathological grading criteria as outlined in the "Guidelines for Pathological Diagnosis of Primary Liver Cancer" and the Eastern Hepatobiliary Surgery Hospital (EHBH) nomogram for predicting MVI are highly recommended. Conclusions We present an expert consensus on the diagnosis and treatment of MVI and potentially improve recurrence-free survival (RFS) and overall survival (OS) for HCC patients with MVI.
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Affiliation(s)
- Juxian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yong Xia
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
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Yang CK, Wei ZL, Shen XQ, Jia YX, Wu QY, Wei YG, Su H, Qin W, Liao XW, Zhu GZ, Peng T. Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy. World J Gastrointest Oncol 2024; 16:4579-4596. [PMID: 39678799 PMCID: PMC11577363 DOI: 10.4251/wjgo.v16.i12.4579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 09/12/2024] [Accepted: 09/29/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) levels in patients with solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following radical resection has not been established. AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBV-related HCC patients. METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed. GPR levels were compared with 908 non-HCC individuals. Overall survival (OS) and recurrence-free survival (RFS) were evaluated, and cox proportional hazard model analyses were performed to identify independent risk factors. Differences in characteristics were adjusted by propensity score matching (PSM). Subgroup and stratified survival analyses for HCC risks were performed, and a linear trend of the hazard ratio (HR) according to GPR levels was constructed. RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas, chronic hepatitis B and healthy control (adjusted P < 0.05). Variable bias was diminished after the PSM balance test. The low GPR group had improved OS (P < 0.001) and RFS (P < 0.001) in the PSM analysis and when combined with other variables. Multivariate cox analyses suggested that low GPR levels were associated with a better OS (HR = 0.5, 95%CI: 0.36-0.7, P < 0.001) and RFS (HR = 0.57, 95%CI: 0.44-0.73, P < 0.001). This same trend was confirmed in subgroup analyses. Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction. Moreover, stratified survival analyses found that GPR > 0.6 was associated with a worse OS and higher recurrence rate (P for trend < 0.001). CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBV-related HCC.
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Affiliation(s)
- Cheng-Kun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhong-Liu Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Qiang Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Xuan Jia
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qiong-Yuan Wu
- Department of Tuina, Nanning Hospital of Traditional Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Yong-Guang Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Shen X, Niu X. Gamma-Glutamyl Transpeptidase to Neutrophil Ratio as Prognostic Indicator for Hepatocellular Carcinoma Patients Post-Curative Resection. J Hepatocell Carcinoma 2024; 11:2077-2085. [PMID: 39483455 PMCID: PMC11526730 DOI: 10.2147/jhc.s478186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/23/2024] [Indexed: 11/03/2024] Open
Abstract
Background The close association between inflammation and the clinical outcomes of hepatocellular carcinoma (HCC) has been extensively documented. This study aims to analyze the association between a novel inflammatory indicator, the gamma-glutamyl transpeptidase to neutrophil ratio (GNR), and HCC prognosis following curative resection. Methods A cohort of 204 eligible HCC cases were included. Based on an optimal cut-off value determined utilizing the X-tile software, patients were categorized into low- and high-GNR groups. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier analysis method with Log rank tests. Multivariate Cox proportional hazard regression was used to investigate the independent association between GNR and HCC prognosis. Restricted cubic splines were used to explore the nonlinear relationship between GNR and the risk of death or recurrence. Results The low GNR group exhibited significantly higher 3-year OS and RFS rates than the high GNR group. Multivariate Cox analysis indicated that a high GNR level was independently associated with poor OS and RFS. A linear correlation between GNR and the risk of death, as well as a nonlinear inverted "U" shape correlation between GNR and the risk of recurrence, were observed. Conclusion The findings provide evidence supporting the independent association of GNR with HCC prognosis. These results offer promise for enhancing prognosis assessments and guiding active monitoring strategies for patients with HCC post-curative resection.
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Affiliation(s)
- Xueqin Shen
- Department of Clinical Nutrition, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China
| | - Xiaoping Niu
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China
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Jiao N, Yan C, He L, Jin HL, Oiu S, Li C, Zheng ZS, Lu B, Wu FD, Yang Y, Chen XG, Zhang Q. Liver transplantation for hepatocellular carcinoma: a proposal for including preoperative serological indicators improves the Milan criteria expanded. Transl Gastroenterol Hepatol 2024; 9:63. [PMID: 39503026 PMCID: PMC11535812 DOI: 10.21037/tgh-24-40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 07/22/2024] [Indexed: 11/08/2024] Open
Abstract
Background Liver transplantation (LT) is the most effective and radical treatment for hepatocellular carcinoma (HCC). Most LT criteria are based on the morphological characteristics of tumors, which are not enough to predict the risk of tumor recurrence. It is found that some serological biomarkers can predict tumor recurrence and may be a good indicator for selecting suitable HCC patients for LT. This article aims to evaluate the predictive effect of preoperative serological indicators on long-term overall survival (OS) and tumor recurrence-free survival (TFS) of patients with HCC after LT, and to explore its significance for expanding the Milan criteria. Methods Clinical data of 253 patients after LT in HCC were collected retrospectively. The receiver operating characteristic curve was used to calculate the best cut-off value. χ2 test was used to analyze the correlation between preoperative serological indicators and tumor pathological features. Univariate and multivariate analyses were used to analyze the risk factors affecting the OS and TFS rates and the predictive values of different LT criteria were compared. Nomogram model was used to predict the OS and TFS rates of patients exceeding Milan criteria. Results Independent risk factors for poor OS and TFS rates were alpha-fetoprotein (AFP) >200 ng/mL, gamma-glutamyl transpeptidase (GGT) >80 IU/L, total tumor diameter (TTD) >8 cm and microsatellite lesions. Nomogram model showed patients beyond Milan criteria had better survival when AFP ≤200 ng/mL and GGT ≤80 IU/L or AFP >200 ng/mL, GGT ≤80 IU/L and TTD ≤8 cm. According to Milan criteria, AFP, GGT and TTD, Milan-AFP-GGT-TTD (M-AGT) criteria was established. There was no significant difference in OS and TFS rates among patients in M-AGT, Milan, Hangzhou, Malaya and the University of California at San Francisco (UCSF) criteria. Conclusions Preoperative serological indicators AFP and GGT can effectively predict long-term OS and TFS in HCC patients after LT. Establishing M-AGT criteria based on serological indicators is helpful to supplement the Milan criteria.
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Affiliation(s)
- Ning Jiao
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
- Department of Health Statistics, Fourth Military Medical University, Xi’an, China
- Department of Gastroenterology, People’s Hospital of Jiyang County, Jinan, China
| | - Cheng Yan
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Li He
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Hai-Long Jin
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shuang Oiu
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Chao Li
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Sheng Zheng
- Department of Orthopaedics, People’s Hospital of Jiyang County, Jinan, China
| | - Bin Lu
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Feng-Dong Wu
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yang Yang
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xin-Guo Chen
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Qing Zhang
- Department of Organ Transplantation, Third Medical Center of Chinese PLA General Hospital, Beijing, China
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Li J, Wang Q, Yan Y, Sun L, Zhang G, Li G, Jin R. Development and validation of a prognostic nomogram to predict the recurrence of AFP-negative and DCP-positive hepatocellular carcinoma after curative resection. Front Oncol 2024; 14:1414083. [PMID: 39175473 PMCID: PMC11338900 DOI: 10.3389/fonc.2024.1414083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/22/2024] [Indexed: 08/24/2024] Open
Abstract
Purpose Approximately one-third of hepatocellular carcinoma (HCC) cases are characterized by alpha-fetoprotein (AFP) negativity (AFP-NHCC. Among these patients, around 60% exhibit des-gamma-carboxyprothrombin (DCP) positivity, and DCP-positive patients have a poorer prognosis. As a curative treatment, recurrence after liver resection poses significant challenges to the prognosis of HCC patients. Therefore, it is necessary to determine the relevant risk factors of these patients and provide timely treatment options. Methods This study included 540 patients who underwent resection at Beijing You'an Hospital. 292 patients from 2014 to 2018 constituted the training cohort, while 248 patients from 2018 to 2020 constituted the validation cohort. All patients underwent routine follow-ups until December 2023. Variables were identified through Cox regression, and a nomogram was developed. The nomogram was evaluated using time-dependent receiver operating characteristic curves (ROC), calibration curves, Decision curve analysis (DCA), and Kaplan-Meier (KM) curve analysis. Results We found that age, tumor number, tumor size, γ-glutamyl transpeptidase (γ-GT), and prothrombin time (PT) are independent risk factors for HCC recurrence, and a nomogram was developed and validated based on this result to predict recurrence-free survival (RFS) at 1, 2, and 3 years. The performance of the nomogram was further confirmed by the ROC curve, calibration curve, and DCA, all of which showed favorable results. The KM curve analysis clearly distinguishes between two groups of people with different risks in terms of prognosis in both the training and validation sets. Conclusion In summary, we established and validated a novel nomogram by multivariate Cox regression analysis to predict recurrence in DCP-positive patients with AFP-NHCC after resection. The nomogram, including age, tumor number, tumor size, γ-GT, and PT, demonstrates better predictive ability for AFP-NHCC patients with DCP positive.
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Affiliation(s)
- Junnan Li
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Qi Wang
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yadong Yan
- People’s Hospital of Donghai County, Lianyungang, China
| | - Lina Sun
- Beijing Institute of Hepatology, Beijing You 'an Hospital, Capital Medical University, Beijing, China
| | - Gongming Zhang
- Department of General Surgery, Beijing You 'an Hospital, Capital Medical University, Beijing, China
| | - Guangming Li
- Department of General Surgery, Beijing You 'an Hospital, Capital Medical University, Beijing, China
| | - Ronghua Jin
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Zhang H, Sheng S, Qiao W, Sun Y, Jin R. Nomogram built based on machine learning to predict recurrence in early-stage hepatocellular carcinoma patients treated with ablation. Front Oncol 2024; 14:1395329. [PMID: 38800405 PMCID: PMC11116608 DOI: 10.3389/fonc.2024.1395329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 04/29/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction To analyze the risk factors affecting recurrence in early-stage hepatocellular carcinoma (HCC) patients treated with ablation and then establish a nomogram to provide a clear and accessible representation of the patients' recurrence risk. Methods Collect demographic and clinical data of 898 early-stage HCC patients who underwent ablation treatment at Beijing You'an Hospital, affiliated with Capital Medical University from January 2014 to December 2022. Patients admitted from 2014 to 2018 were included in the training cohort, while 2019 to 2022 were in the validation cohort. Lasso and Cox regression was used to screen independent risk factors for HCC patients recurrence, and a nomogram was then constructed based on the screened factors. Results Age, gender, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, globulin (Glob) and γ-glutamyl transpeptidase (γ-GT) were finally incorporated in the nomogram for predicting the recurrence-free survival (RFS) of patients. We further confirmed that the nomogram has optimal discrimination, consistency and clinical utility by the C-index, Receiver Operating Characteristic Curve (ROC), calibration curve and Decision Curve Analysis (DCA). Moreover, we divided the patients into different risk groups and found that the nomogram can effectively identify the high recurrence risk patients by the Kaplan-Meier curves. Conclusion This study developed a nomogram using Lasso-Cox regression to predict RFS in early-stage HCC patients following ablation, aiding clinicians in identifying high-risk groups for personalized follow-up treatments.
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Affiliation(s)
- Honghai Zhang
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Shugui Sheng
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wenying Qiao
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Yu Sun
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Ronghua Jin
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
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Luo XY, Chang KW, Ye N, Gao CH, Zhu QB, Liu JP, Zhou X, Zheng SS, Yang Z. The predictive value of γ-glutamyl transferase to serum albumin ratio in hepatocellular carcinoma patients after liver transplantation. Front Med (Lausanne) 2024; 11:1380750. [PMID: 38799149 PMCID: PMC11122022 DOI: 10.3389/fmed.2024.1380750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 04/08/2024] [Indexed: 05/29/2024] Open
Abstract
Background Elevated preoperative γ-glutamyl transferase (GGT) levels or reduced serum albumin levels have been established as negative prognostic factors for patients with hepatocellular carcinoma (HCC) and various other tumors. Nonetheless, the prognostic significance of the GGT to serum albumin ratio (GAR) in liver transplantation (LT) therapy for HCC is still not well-defined. Methods A retrospective analysis was conducted on the clinical data of 141 HCC patients who underwent LT at Shulan (Hangzhou) Hospital from June 2017 to November 2020. Using the receiver operating characteristic (ROC) curve, the optimal GAR cutoff value to predict outcomes following LT was assessed. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent risk factors associated with both overall survival (OS) and recurrence-free survival (RFS). Results A GAR value of 2.04 was identified as the optimal cutoff for predicting both OS and RFS, with a sensitivity of 63.2% and a specificity of 74.8%. Among these patients, 80 (56.7%) and 90 (63.8%) met the Milan and the University of California San Francisco (UCSF) criteria, respectively. Univariate Cox regression analysis showed that microvascular invasion (MVI), maximum tumor size (>5 cm), total tumor size (>8 cm), liver cirrhosis, TNM stage (III), and GAR (≥2.04) were significantly associated with both postoperative OS and RFS in patients with HCC (all p < 0.05). Multivariate Cox regression analysis indicated that GAR (≥2.04) was independently linked with RFS and OS. Conclusion Pre-transplant GAR ≥2.04 is an independent correlate of prognosis and survival outcomes after LT for HCC and can be used as a prognostic indicator for both mortality and tumor recurrence following LT.
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Affiliation(s)
- Xing-Yu Luo
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Kai-Wun Chang
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Nan Ye
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Chen-Hao Gao
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qing-Bo Zhu
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jian-Peng Liu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xing Zhou
- MSK Laboratory, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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Wang F, Yan CY, Qin Y, Wang ZM, Liu D, He Y, Yang M, Wen L, Zhang D. Multiple Machine-Learning Fusion Model Based on Gd-EOB-DTPA-Enhanced MRI and Aminotransferase-to-Platelet Ratio and Gamma-Glutamyl Transferase-to-Platelet Ratio to Predict Microvascular Invasion in Solitary Hepatocellular Carcinoma: A Multicenter Study. J Hepatocell Carcinoma 2024; 11:427-442. [PMID: 38440051 PMCID: PMC10911084 DOI: 10.2147/jhc.s449737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 02/20/2024] [Indexed: 03/06/2024] Open
Abstract
Background Currently, it is still confused whether preoperative aminotransferase-to-platelet ratio (APRI) and gamma-glutamyl transferase-to-platelet ratio (GPR) can predict microvascular invasion (MVI) in solitary hepatocellular carcinoma (HCC). We aimed to develop and validate a machine-learning integration model for predicting MVI using APRI, GPR and gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI. Methods A total of 314 patients from XinQiao Hospital of Army Medical University were divided chronologically into training set (n = 220) and internal validation set (n = 94), and recurrence-free survival was determined to follow up after surgery. Seventy-three patients from Chongqing University Three Gorges Hospital and Luzhou People's Hospital served as external validation set. Overall, 387 patients with solitary HCC were analyzed as whole dataset set. Least absolute shrinkage and selection operator, tenfold cross-validation and multivariate logistic regression were used to gradually filter features. Six machine-learning models and an ensemble of the all models (ENS) were built. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model's performance. Results APRI, GPR, HBPratio3 ([liver SI‒tumor SI]/liver SI), PLT, peritumoral enhancement, non-smooth margin and peritumoral hypointensity were independent risk factors for MVI. Six machine-learning models showed good performance for predicting MVI in training set (AUCs range, 0.793-0.875), internal validation set (0.715-0.832), external validation set (0.636-0.746) and whole dataset set (0.756-0.850). The ENS achieved the highest AUCs (0.879 vs 0.858 vs 0.839 vs 0.851) in four cohorts with excellent calibration and more net benefit. Subgroup analysis indicated that ENS obtained excellent AUCs (0.900 vs 0.809 vs 0.865 vs 0.908) in HCC >5cm, ≤5cm, ≤3cm and ≤2cm cohorts. Kaplan‒Meier survival curves indicated that ENS achieved excellent stratification for MVI status. Conclusion The APRI and GPR may be new potential biomarkers for predicting MVI of HCC. The ENS achieved optimal performance for predicting MVI in different sizes HCC and may aid in the individualized selection of surgical procedures.
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Affiliation(s)
- Fei Wang
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
- Department of Medical Imaging, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China
| | - Chun Yue Yan
- Department of Emergency Medicine, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China
| | - Yuan Qin
- Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing, 404031, People’s Republic of China
| | - Zheng Ming Wang
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
| | - Dan Liu
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
| | - Ying He
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
| | - Ming Yang
- Department of Medical Imaging, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China
| | - Li Wen
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
| | - Dong Zhang
- Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China
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Zhang L, Li S, Zhang D, Yin C, Wang Z, Chen R, Cheng N, Bai Y. Value of GPR, APPRI and FIB-4 in the early diagnosis of hepatocellular carcinoma: a prospective cohort study. Jpn J Clin Oncol 2024; 54:129-136. [PMID: 37869774 DOI: 10.1093/jjco/hyad147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 10/05/2023] [Indexed: 10/24/2023] Open
Abstract
OBJECTIVE There is an urgent need for novel biomarkers that are inexpensive, effective and easily accessible to complement the early diagnosis of hepatocellular carcinoma. This study aimed to analyze the relationship between serum gamma-glutamate-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index, fibrosis index based on four factors and the risk of hepatocellular carcinoma, and to determine the optimal cut-offs for predicting hepatocellular carcinoma. METHODS Based on a prospective cohort study, 44 215 participants who were cancer-free at baseline (2011-13) were included in the study. Cox proportional hazard models and receiver operating characteristics curves were used to analyze the diagnostic value and optimal cut-off value of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors in predicting hepatocellular carcinoma patients. RESULTS Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors can be used as early independent predictors of hepatocellular carcinoma risk. The risk of hepatocellular carcinoma in the fourth quantile of gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index was 4.04 times (hazard ratio = 4.04, 95% confidence interval: 2.09, 7.80) and 2.59 times (hazard ratio = 2.59, 95% confidence interval: 1.45, 4.61), respectively, compared with the first quantile. With fibrosis index based on four factors first quantile as a reference, fibrosis index based on four factors fourth quantile had the highest risk (hazard ratio = 18.58, 95% confidence interval: 7.55, 45.72). Receiver operating characteristic results showed that fibrosis index based on four factors had a stronger ability to predict the risk of hepatocellular carcinoma (area under curve = 0.81, 95% confidence interval: 0.80, 0.81), and similar results were shown for gender stratification. In the total population, the optimal cut-off values of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were 0.208, 0.629 and 1.942, respectively. CONCLUSIONS Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were independent predictors of hepatocellular carcinoma risk. Amongst them, fibrosis index based on four factors shows a stronger predictive ability for hepatocellular carcinoma risk, and gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index can be used as complementary indicators.
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Affiliation(s)
- Lizhen Zhang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, China
| | - Siyu Li
- Department of Epidemiology, Baotou Medical College, Baotou, China
| | - Desheng Zhang
- Jinchuan Group Co., LTD, Jinchuan Company Staff Hospital, Jinchang, China
| | - Chun Yin
- Jinchuan Group Co., LTD, Jinchuan Company Staff Hospital, Jinchang, China
| | - Zhongge Wang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, China
| | - Ruirui Chen
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, China
| | - Ning Cheng
- College of Basic Medicine, Lanzhou University, Lanzhou, China
| | - Yana Bai
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, China
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Patidar Y, Meena G, Mukund A, Sharma MK, Sarin SK. Association of Serum ɣ-Glutamyl Transpeptidase Levels With Overall Survival in Intermediate and Advanced Hepatocellular Carcinoma Treated With Transarterial Chemoembolization. J Clin Exp Hepatol 2023; 13:934-945. [PMID: 37975060 PMCID: PMC10643513 DOI: 10.1016/j.jceh.2023.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 04/26/2023] [Indexed: 11/19/2023] Open
Abstract
Introduction This article aims to evaluate the prognostic significance of pretreatment serum ɣ-glutamyl transpeptidase (GGT) levels in patients with intermediate (BCLC B) and advanced stage (BCLC C) hepatocellular carcinoma receiving transarterial chemoembolization (TACE) as first-line treatment. Methods In this single-center retrospective study, a total of 608 patients with BCLC B and BCLC C class were included who received TACE as first-line treatment modality. Patients were divided into low and high GGT groups based on a cutoff value of pretreatment serum GGT levels calculated by receiver operating curve. Overall survival was evaluated with Kaplan-Meier method, and intergroup significance was calculated by log-rank test for overall patients, each BCLC B and BCLC C group. Univariate and multivariate analysis were used for significance for prognostic factors. Results Median follow-up time was 20, 22, and 9 months for overall patients, BCLC B, and BCLC C group, respectively. Optimal cut value for GGT was calculated at 90.5 U/L. One-year and 3-year survival rates were 84.2% and 27.9% in low GGT, 49.4% and 8.6% in high-GGT group for overall patients. Multivariate analysis in overall patients showed Child-Pugh B (HR,1.801; 95%CI, 1.373-2.362, P < .001), ascites (1.393, 1.070-1.812; P = .014), multiple tumors (1.397, 1.137-1.716; P = .001), AST >40 (1.407, 1.095-1.808; P = .008), albumin <3.2 (.735, .612-.884; P = .001), AFP > 400 (1.648, 1.351-2.011; P < .001), high GGT (2.009, 1.631-2.475; P < .001), or receipt of chemo/ablation (.463, .377-.569; P < .001) as independent risk factors for overall survival. Serum GGT levels and AFP showed significant correlation in between with significance coefficient of .155 (P < .001). Conclusion Elevated pretreatment serum GGT level was feasible and promising independent prognostic marker for overall survival in intermediate and advanced stage hepatocellular carcinoma patients treated with TACE.
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Affiliation(s)
- Yashwant Patidar
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi-110070, India
| | - Gaurav Meena
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi-110070, India
| | - Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi-110070, India
| | - Manoj K. Sharma
- Department of Hepatology, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi-110070, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi-110070, India
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Wu Q, Zeng J, Zeng J. Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection. J Hepatocell Carcinoma 2023; 10:193-202. [PMID: 36789253 PMCID: PMC9922487 DOI: 10.2147/jhc.s393286] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 01/20/2023] [Indexed: 02/10/2023] Open
Abstract
Background The role of inflammation-related markers in alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) is not well known. This study aimed to investigate the clinical significance of inflammation-related markers in AFP-negative HCC patients after curative resection. Methods One thousand one hundred and seventy-nine AFP-negative HCC patients after curative resection were included. Survival rate and prognostic analysis were performed using Kaplan-Meier and Cox regression analysis. Propensity score matching (PSM) was used for patient selection. Results Multivariate Cox regression showed that neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NrLR) was the independent risk factor associated with OS (p = 0.002) and RFS (p = 0.017). Low NrLR groups (n = 628) had lower rates of albumin-bilirubin (ALBI) grade 2 (p < 0.001), lower rates of bleeding and blood transfusion (p < 0.001) than high NrLR groups. Considering tumor features, low NrLR groups had lower AFP levels (p < 0.001), smaller tumor size (p < 0.001), and lower rates of Edmondson grade III-IV (p = 0.024) than high NrLR groups. After PSM, the 1-year, 3 year-, and 5-year OS rates in the low NrLR and high NrLR groups were 96.3%, 86.9%, 64.9%, and 91.4%, 76.7%, 59.5% (p < 0.001), respectively. The 1-year, 3-year, and 5-year RFS rates in the low NrLR and high NrLR groups were 80.0%, 62.9%, 47.5%, and 71.7%, 52.6%, 39.5% (p < 0.001), respectively. Conclusion NrLR was a poor prognostic factor for mortality and tumor recurrence in AFP-negative HCC patients after curative resection. The simple and low-cost marker could help physician to determine patients at high risk of tumor recurrence for frequent clinical surveillance.
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Affiliation(s)
- Qionglan Wu
- Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China,Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
| | - Jinhua Zeng
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China,Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China,Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
| | - Jianxing Zeng
- Hepatobiliary Medical Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China,Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China,Correspondence: Jianxing Zeng, Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel/Fax +86 591 8811 6010, Email
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Xu L, Chen L, Zhang B, Liu Z, Liu Q, Liang H, Chen Y, Chen X, Leng C, Zhang B. Alkaline phosphatase combined with γ-glutamyl transferase is an independent predictor of prognosis of hepatocellular carcinoma patients receiving programmed death-1 inhibitors. Front Immunol 2023; 14:1115706. [PMID: 36761721 PMCID: PMC9905229 DOI: 10.3389/fimmu.2023.1115706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 01/09/2023] [Indexed: 01/27/2023] Open
Abstract
Background Immunotherapy plays an increasingly critical role in the systemic treatment of HCC. This current study aimed to establish a novel prognostic predictor of Programmed death 1 (PD-1) inhibitor therapy in hepatocellular carcinoma (HCC) independent of Child-Pugh grade. Methods Our study screened patients with HCC who received PD-1 inhibitors at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2018 to December 2020. ALG grade was determined by the patient's serum ALP and GGT levels before the initiation of PD-1 inhibitors. The endpoints of our study were overall survival (OS) and progression free survival (PFS). Follow-up ended at May 31, 2022. Results Eighty- five patients (77 with Child-Pugh grade A, 8 with Child-Pugh grade B at baseline) were enrolled according to the inclusion criteria. Patients with Child-Pugh grade A achieved longer PFS and OS than those with Child-Pugh grade B. Patients with ALG grade 3 at baseline showed worse tumor response and poorer survival, and ALG grade could stratify patients with Child-Pugh grade A into subgroups with significantly different prognosis. Conclusions ALG grade, combining ALP and GGT, is a novel and readily available prognostic marker and the predictive effect of ALG grade on patient prognosis is independent of Child-Pugh grade.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bin Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhichen Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qiumeng Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huifang Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yifa Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Xiaoping Chen, ; Chao Leng, ; Bixiang Zhang,
| | - Chao Leng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Xiaoping Chen, ; Chao Leng, ; Bixiang Zhang,
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China,*Correspondence: Xiaoping Chen, ; Chao Leng, ; Bixiang Zhang,
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Zhao JW, Shu X, Chen XX, Liu JX, Liu MQ, Ye J, Jiang HJ, Wang GS. Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram. Hepatobiliary Pancreat Dis Int 2022; 21:543-550. [PMID: 35705443 DOI: 10.1016/j.hbpd.2022.05.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 05/24/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT. METHODS A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram. RESULTS There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model. CONCLUSIONS Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.
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Affiliation(s)
- Jing-Wei Zhao
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, The Training Site for Postgraduate of Jinzhou Medical University, Beijing 100039, China; Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Xin Shu
- Medical School of Chinese PLA, Beijing 100853, China
| | - Xiao-Xia Chen
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Jia-Xiong Liu
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Mu-Qing Liu
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Ju Ye
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
| | - Hui-Jie Jiang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
| | - Gui-Sheng Wang
- Department of Radiology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China.
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Lozanovski VJ, Ramouz A, Aminizadeh E, Al-Saegh SAH, Khajeh E, Probst H, Picardi S, Rupp C, Chang DH, Probst P, Mehrabi A. Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis. BJS Open 2022; 6:zrab130. [PMID: 35211739 PMCID: PMC8874238 DOI: 10.1093/bjsopen/zrab130] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/27/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Heike Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Susanne Picardi
- Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Rupp
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - De-Hua Chang
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
- Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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Li H, Hai Z, Zou L, Zhang L, Wang L, Wang L, Liang G. Simultaneous enhancement of T 1 and T 2 magnetic resonance imaging of liver tumor at respective low and high magnetic fields. Theranostics 2022; 12:410-417. [PMID: 34987653 PMCID: PMC8690926 DOI: 10.7150/thno.67155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/27/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Nowadays, magnetic resonance imaging (MRI) is routinely applied in clinical diagnosis. However, using one contrast agent (CA) to simultaneously enhance the T1 and T2 MR contrast at low and high magnetic fields respectively has not been reported. Methods: Herein, we investigated the MR property of a γ-glutamyl transpeptidase (GGT)-instructed, intracellular formed gadolinium nanoparticle (DOTA-Gd-CBT-NP) at low and high magnetic fields. Results: Experimental results showed that DOTA-Gd-CBT-NP possesses a low r2/r1 ratio 0.91 which enables it to enhance T1 MR imaging of liver tumor at 1.0 T, and a high r2/r1 ratio 11.8 which renders the nanoparticle to largely enhance T2 MR imaging of liver tumor at 9.4 T. Conclusion: We expect that our GGT-responsive Gd-nanoparticle could be applied for simultaneous T1 and T2 MRI diagnosis of early liver cancer in clinic at respective low and high magnetic fields when the 9.4 T MR machine is clinically available in the future.
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Affiliation(s)
- Huan Li
- Department of Radiology, the Second Hospital of Anhui Medical University, Hefei, Anhui 230601, China
| | - Zijuan Hai
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Liwei Zou
- Department of Radiology, the Second Hospital of Anhui Medical University, Hefei, Anhui 230601, China
| | - Lele Zhang
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China
| | - Lulu Wang
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China
| | - Longsheng Wang
- Department of Radiology, the Second Hospital of Anhui Medical University, Hefei, Anhui 230601, China
| | - Gaolin Liang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
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Zhang Q, Jiao X. LDH and GGT/ALT Ratio as Novel Prognostic Biomarkers in Hepatocellular Carcinoma Patients after Liver Transplantation. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2021; 2021:9809990. [PMID: 34845414 PMCID: PMC8627343 DOI: 10.1155/2021/9809990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 11/01/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Liver inflammation indices reflect its inflammatory microenvironment, which may play a role in the proliferation, invasion, and migration of carcinoma. This study is aimed at exploring the prognostic significance of serum lactate dehydrogenase (LDH) levels and gamma-glutamyl transferase (GGT)/alanine aminotransferase (ALT) ratio in hepatocellular carcinoma after liver transplant (LT). METHODS We retrospectively analyzed data from 155 patients with a pathologically confirmed diagnosis of hepatocellular carcinoma who received LT between January 2013 and September 2017. We used receiver operating characteristics (ROC) curves to determine the optimal LDH and GGT/ALT ratio cut-off values. The Kaplan-Meier method and the logarithmic rank test were used to compare the survival curves without recurrence (RFS) and overall survival (OS). Univariate and multivariate analyses were used to identify factors associated with survival. RESULTS Serum LDH levels were significantly associated with the Child-Pugh score (P = 0.037), largest tumor size (<50 vs. ≥50 mm) (P = 0.017), tumor count (<3 vs. ≥3) (P = 0.009), microvascular invasion (P = 0.006), and the Milan criteria (P ≤ 0.001). The serum GGT/ALT ratio was significantly correlated with alpha-fetoprotein (AFP) levels (of <400 vs. ≥400 ng/ml) (P ≤ 0.001), largest tumor size (of <50 vs. ≥50 mm) (P ≤ 0.001), the Edmondson grade (I-II vs. III-IV) (P = 0.028), microvascular invasion (P ≤ 0.001), and the Milan (P = 0.002) and Hangzhou criteria (P = 0.018). The survival curves showed that the patients with high LDH and the GGT/ALT ratio were associated with poor RFS and OS (P < 0.05). Univariate and multivariate analyses showed that AFP levels of ≥400 ng/ml, largest tumor size of ≥50 mm, microvascular invasion, LDH levels of ≥213.5 U/l, and the GGT/ALT ratio of ≥3.1338 were factors independently associated with RFS. CONCLUSION Elevated LDH levels and the GGT/ALT ratio before LT were associated with poor OS and RFS in the present study. These factors could be used in the prognostication of patients with hepatocellular carcinoma undergoing LT.
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Affiliation(s)
- Qi Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xingyuan Jiao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Bioinformatic Evidence Reveals that Cell Cycle Correlated Genes Drive the Communication between Tumor Cells and the Tumor Microenvironment and Impact the Outcomes of Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2021; 2021:4092635. [PMID: 34746301 PMCID: PMC8564189 DOI: 10.1155/2021/4092635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 09/04/2021] [Indexed: 12/27/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein–protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan–Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes' expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.
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Jiang T, Lyu SC, Zhou L, Wang J, Li H, He Q, Lang R. Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma. World J Gastrointest Surg 2021; 13:1025-1038. [PMID: 34621478 PMCID: PMC8462080 DOI: 10.4240/wjgs.v13.i9.1025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 06/18/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Distal cholangiocarcinoma (DCC) presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis. Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies. Therefore, it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma.
AIM To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9 (CA19-9) level by adapting CA19-9 to γ-glutamyltransferase (GGT) as an indicator, to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC.
METHODS We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital. Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival. Based on this, patients were divided into two groups (group 1, low-ratio, n = 81; group 2, high-ratio, n = 105). Afterwards, by the way of univariate and multivariate analysis, the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out.
RESULTS Optimum cut-off value of CA19-9/GGT was 0.12. Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT, when compared with group 1 (P < 0.05). The 1-, 3- and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%, 59.2% and 48.1%, and 61.0%, 13.6% and 13.6%, respectively (P = 0.000). Multivariate analysis indicated that CA19-9/GGT, lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC.
CONCLUSION Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.
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Affiliation(s)
- Tao Jiang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Lin Zhou
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Jing Wang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Han Li
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
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Xu L, Leng C, Chen L, Dong H, Chen Y, Chen X. Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinoma. Int J Cancer 2021; 150:472-481. [PMID: 34536292 DOI: 10.1002/ijc.33813] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/13/2021] [Accepted: 09/09/2021] [Indexed: 12/19/2022]
Abstract
Programmed death 1 (PD-1) inhibitors are widely used for treatment of hepatocellular carcinoma (HCC). Hypothyroidism is commonly associated with this therapy, although the mechanism underlying this complication and effects on patient prognosis remain unclear. We retrospectively analysed the data of patients with HCC who received anti-PD-1 therapy at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 2018 and May 2020. Based on thyroid function evaluation, patients were categorised into hypothyroidism group and nonhypothyroidism group. Follow-up was completed on February 28, 2021. The primary endpoint of our study was progression free survival (PFS). The study included 74 patients, and the disease control rate was higher in hypothyroidism group (62.7%, 27/43) than in nonhypothyroidism group (36.4%, 11/31) (P = .020). The PFS was longer in hypothyroidism group (7.44 months) than in nonhypothyroidism group (5.68 months) (P = .006). Additionally, the PFS of patients with hypothyroidism before immunotherapy (6.27 months) was also longer than that in nonhypothyroidism group (5.68 months), although the difference was statistically nonsignificant (P = .527). Cox regression analysis showed that the hazard ratios of hypothyroidism, Child-Pugh grade B at initial admission and serum gamma-glutamyl transferase levels >71 U/L before immunotherapy were 0.404 (95% confidence interval [CI]: 0.207-0.791, P = .008), 2.753 (95%CI: 1.127-6.455, P = .026) and 2.469 (95%CI: 1.155-5.277, P = .020), respectively. Hypothyroidism was associated with prognosis in patients with HCC treated with PD-1 inhibitors, and prognosis was more favourable in patients with hypothyroidism than in those without hypothyroidism. Hypothyroidism and the Child-Pugh grade at initial admission were independently associated with patient prognosis.
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Affiliation(s)
- Lei Xu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chao Leng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lin Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hanhua Dong
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yifa Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Lyu SC, Wang J, Huang M, Wang HX, Zhou L, He Q, Lang R. CA19-9 Level to Serum γ-Glutamyltransferase as a Potential Prognostic Biomarker in Patients with Pancreatic Head Carcinoma. Cancer Manag Res 2021; 13:4887-4898. [PMID: 34188542 PMCID: PMC8232842 DOI: 10.2147/cmar.s313517] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/19/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The aim of this study was to reduce the influence of biliary obstruction on carbohydrate antigen 19-9 level (CA19-9) by introducing the CA19-9 level to serum γ-glutamyltransferase (GGT) ratio as an indicator, and ultimately to reveal the correlation between CA19-9/GGT and the prognosis of patients with pancreatic head carcinoma (PHC). METHODS A total of 339 enrolled patients who underwent pancreatoduodenectomy for PHC in Beijing ChaoYang Hospital from January 2010 to December 2019 were analyzed retrospectively. The optimal cut-off value, according to which patients were divided into a low-ratio group (Group 1, n=179) and a high-ratio group (Group 2, n=160), was determined by the ROC curve obtained from preoperative CA19-9/GGT and 1-year survival. Through univariate and multivariate analyses, risk factors for postoperative tumor recurrence and long-term survival were screened out among PHC patients. RESULTS The best cut-off value of CA19-9/GGT was 2.07 (area under the curve=0.567, 95% CI 0.498-0.636). Compared with Group 2, Group 1 had lower CA19-9, and higher GGT, total bilirubin (TB) and lymph-node metastasis rate (P<0.05). The 1-, 2- and 3-year disease-free survival rates of patients in Groups 1 and 2 were 68.2%, 42.5% and 28.2%, and 42.2%, 19.3% and 18.3%, respectively (P=0.000), and the 1-, 2- and 3-year overall survival rates were 79.1%, 50.7% and 29.1%, and 56.7%, 22.2% and 17.2%, respectively (P=0.000). Multivariate analysis showed that CA19-9/GGT, portal system invasion and lymph-node metastasis were independent risk factors for postoperative tumor recurrence and long-term survival among patients with PHC. CONCLUSION Compared with CA19-9 level alone, CA19-9/GGT plays a more precise role in the evaluation of postoperative tumor recurrence and the long-term prognosis of PHC patients. The lower the ratio, the better the long-term prognosis. The CA19-9/GGT ratio may prove to be a useful biomarker for identifying PHC patients at high risk of early recurrence and unfavorable prognosis.
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Affiliation(s)
- Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Jing Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Mengxiu Huang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Han-Xuan Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
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Han Y, Park IS, Kim SI, Wang W, Yoo J, Jo H, Lee J, Seol A, Han KD, Song YS. Increasing serum gamma-glutamyltransferase level accompanies a rapid increase in the incidence of endometrial cancer in Korea: A nationwide cohort study. Gynecol Oncol 2021; 161:864-870. [PMID: 33795129 DOI: 10.1016/j.ygyno.2021.03.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 03/23/2021] [Indexed: 01/05/2023]
Abstract
OBJECTIVE This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis. METHODS We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588). RESULTS Obese (BMI, ≥25 kg/m2) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227). CONCLUSIONS Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.
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Affiliation(s)
- Youngjin Han
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea; SK Biopharmaceuticals Co., Ltd., Seongnam-si, Gyeonggi-do 13494, Republic of Korea
| | - In Sil Park
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Wenyu Wang
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Interdisciplinary Program in Cancer Biology, Seoul National University, Seoul 03080, Republic of Korea
| | - Juhwan Yoo
- Department of Biomedicine & Health Science, The Catholic University of Korea, Seoul, Republic of Korea
| | - HyunA Jo
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea
| | - Juwon Lee
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea
| | - Aeran Seol
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Yong Sang Song
- Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
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Jin H, Wang H, Li G, Hou Q, Wu W, Liu F. Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma. J Int Med Res 2021; 48:300060520961260. [PMID: 33044114 PMCID: PMC7556173 DOI: 10.1177/0300060520961260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Objective To investigate the risk factors of early postoperative recurrence in patients with single and small (≤3 cm) hepatitis B virus-associated primary hepatocellular carcinoma (HBV-HCC). Methods This retrospective study analyzed patients with single and small HBV-HCC. All patients were followed up for 1 year after surgery. Results Among 182 patients, 54 patients had early recurrence within 1 year. The recurrence group had higher proportions of men, drinking history, Child–Turcotte–Pugh (CTP) class C, patients who underwent transarterial chemoembolization (TACE), and serum alpha-fetoprotein (AFP) >10 ng/mL as well as higher gamma-glutamyl transpeptidase (GGT) levels and lower total protein (TP) and CD8+ T lymphocyte levels than the no recurrence group. Cox multivariate regression analysis demonstrated that drinking history (HR, 1.312; 95% CI, 1.042–1.652), CTP class C (HR, 1.236; 95% CI, 1.037–1.473), TACE treatment (HR, 1.241; 95% CI, 1.026–1.501), GGT (HR, 1.138; 95% CI, 1.042–1.243), TP (HR, 0.729; 95% CI, 0.555–0.957), and AFP (HR, 2.519; 95% CI, 1.343–4.726) were independently associated with early postoperative recurrence. Conclusion Drinking history, CTP class C, TACE, serum AFP, GGT, and TP levels were independently associated with early postoperative recurrence in patients with single and small HBV-HCC.
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Affiliation(s)
- Hongmei Jin
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Hui Wang
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Guanghao Li
- Department of Hepatobiliary surgery, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Qingshun Hou
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Wei Wu
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
| | - Fuhui Liu
- Department of Hepatology, Qingdao No. 6 People's Hospital, Qingdao, Shandong, China
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Sun L, Ke X, Wang D, Yin H, Jin B, Xu H, Du S, Xu Y, Zhao H, Lu X, Sang X, Zhong S, Yang H, Mao Y. Prognostic Value of the Albumin-to-γ-glutamyltransferase Ratio for Gallbladder Cancer Patients and Establishing a Nomogram for Overall Survival. J Cancer 2021; 12:4172-4182. [PMID: 34093818 PMCID: PMC8176430 DOI: 10.7150/jca.49242] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 04/23/2021] [Indexed: 01/05/2023] Open
Abstract
Purpose: The albumin-to-γ-glutamyltransferase ratio (AGR), a novel inflammation-related index, has been reported to have prognostic importance in several malignancies but not yet in gallbladder cancer (GBC). This study intended to assess the prognostic value of AGR in GBC and to develop a nomogram based on AGR for predicting overall survival (OS) in GBC patients after surgery. Methods: Medical records of 140 qualified GBC patients between July 2003 and June 2017 were retrospectively analyzed. The function “surv_cutpoint” in the R package “survminer” was implemented to discover the optimal cut-off value of AGR. A nomogram on the fundamental of Cox model was established in the training cohort and was internally validated using calibration curves, Harrell's concordance index, time-dependent AUC plots and decisive curve analyses. Results: The optimal AGR cut-off value concerning overall survival was 2.050. Univariate and multivariate analyses demonstrated that AGR (HR=0.354, P=0.004), T stage (HR=3.114, P=0.004), R0 resection (HR=0.448, P=0.003), BMI (HR=0.470, P=0.002) and CA19-9 (HR=1.704, P=0.048) were independent predictors for OS. The nomogram combining these prognostic factors showed considerable prognostic performance in term of consistency, discrimination and net benefit. Conclusion: AGR has independent prognostic value for OS in GBC patients receiving surgery. A nomogram incorporating AGR, T stage, R0 resection, CA19-9 and BMI achieved enhanced prognostic ability.
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Affiliation(s)
- Lejia Sun
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xindi Ke
- Peking Union Medical College (PUMC), PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Dongyue Wang
- Peking Union Medical College (PUMC), PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huanhuan Yin
- Peking Union Medical College (PUMC), PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Shouxian Zhong
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, 100730, China
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AGLR is a novel index for the prognosis of hepatocellular carcinoma patients: a retrospective study. BMC Surg 2021; 21:72. [PMID: 33536005 PMCID: PMC7860009 DOI: 10.1186/s12893-020-01037-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/27/2020] [Indexed: 02/08/2023] Open
Abstract
Background Most hepatocellular carcinoma (HCC) patients’ liver function indexes are abnormal. We aimed to investigate the relationship between (alkaline phosphatase + gamma-glutamyl transpeptidase)/lymphocyte ratio (AGLR) and the progression as well as the prognosis of HCC. Methods A total of 495 HCC patients undergoing radical hepatectomy were retrospectively analyzed. We randomly divided these patients into the training cohort (n = 248) and the validation cohort (n = 247). In the training cohort, receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of AGLR for predicting postoperative survival of HCC patients, and the predictive value of AGLR was evaluated by concordance index (C-index). Further analysis of clinical and biochemical data of patients and the correlation analysis between AGLR and other clinicopathological factors were finished. Univariate and multivariate analyses were performed to identify prognostic factors for HCC patients. Survival curves were analyzed using the Kaplan–Meier method. Results According to the ROC curve analysis, the optimal predictive cut-off value of AGLR was 90. The C-index of AGLR was 0.637 in the training cohort and 0.654 in the validation cohort, respectively. Based on this value, the HCC patients were divided into the low-AGLR group (AGLR ≤ 90) and the high-AGLR group (AGLR > 90). Preoperative AGLR level was positively correlated with alpha-fetoprotein (AFP), tumor size, tumor-node-metastasis (TNM) stage, and microvascular invasion (MVI) (all p < 0.05). In the training and validation cohorts, patients with AGLR > 90 had significantly shorter OS than patients with AGLR ≤ 90 (p < 0.001). Univariate and multivariate analyses of the training cohort (HR, 1.79; 95% CI 1.21–2.69; p < 0.001) and validation cohort (HR, 1.82; 95% CI 1.35–2.57; p < 0.001) had identified AGLR as an independent prognostic factor. A new prognostic scoring model was established based on the independent predictors determined in multivariate analysis. Conclusions The elevated preoperative AGLR level indicated poor prognosis for patients with HCC; the novel prognostic scoring model had favorable predictive capability for postoperative prognosis of HCC patients, which may bring convenience for clinical management.
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Liu X, Lu J, Zhang G, Han J, Zhou W, Chen H, Zhang H, Yang Z. A Machine Learning Approach Yields a Multiparameter Prognostic Marker in Liver Cancer. Cancer Immunol Res 2021; 9:337-347. [PMID: 33431375 DOI: 10.1158/2326-6066.cir-20-0616] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 11/13/2020] [Accepted: 01/07/2021] [Indexed: 01/19/2023]
Abstract
A number of staging systems have been developed to predict clinical outcomes in hepatocellular carcinoma (HCC). However, no general consensus has been reached regarding the optimal model. New approaches such as machine learning (ML) strategies are powerful tools for incorporating risk factors from multiple platforms. We retrospectively reviewed the baseline information, including clinicopathologic characteristics, laboratory parameters, and peripheral immune features reflecting T-cell function, from three HCC cohorts. A gradient-boosting survival (GBS) classifier was trained with prognosis-related variables in the training dataset and validated in two independent cohorts. We constructed a 20-feature GBS model classifier incorporating one clinical feature, 14 laboratory parameters, and five T-cell function parameters obtained from peripheral blood mononuclear cells. The GBS model-derived risk scores demonstrated high concordance indexes (C-indexes): 0.844, 0.827, and 0.806 in the training set and validation sets 1 and 2, respectively. The GBS classifier could separate patients into high-, medium- and low-risk subgroups with respect to death in all datasets (P < 0.05 for all comparisons). A higher risk score was positively correlated with a higher clinical stage and the presence of portal vein tumor thrombus (PVTT). Subgroup analyses with respect to Child-Pugh class, Barcelona Clinic Liver Cancer stage, and PVTT status supported the prognostic relevance of the GBS-derived risk algorithm independent of the conventional tumor staging system. In summary, a multiparameter ML algorithm incorporating clinical characteristics, laboratory parameters, and peripheral immune signatures offers a different approach to identify patients with the greatest risk of HCC-related death.
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Affiliation(s)
- Xiaoli Liu
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Jilin Lu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, P.R. China
| | - Guanxiong Zhang
- Genecast Precision Medicine Technology Institute, Beijing, P.R. China
| | - Junyan Han
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China
| | - Wei Zhou
- Genecast Precision Medicine Technology Institute, Beijing, P.R. China
| | - Huan Chen
- Genecast Precision Medicine Technology Institute, Beijing, P.R. China.
| | - Henghui Zhang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China.
| | - Zhiyun Yang
- Center for Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, P.R. China.
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Ince V, Carr BI, Bag HG, Ersan V, Usta S, Koc C, Gonultas F, Sarici BK, Karakas S, Kutluturk K, Baskiran A, Yilmaz S. Liver transplant for large hepatocellular carcinoma in Malatya: The role of gamma glutamyl transferase and alpha-fetoprotein, a retrospective cohort study. World J Gastrointest Surg 2020; 12:520-533. [PMID: 33437403 PMCID: PMC7769743 DOI: 10.4240/wjgs.v12.i12.520] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/03/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is increasing interest in transplanting patients with hepatocellular carcinoma (HCC) with tumors greater than 5 cm (Milan criteria). AIM To investigate possible prognostically-useful factors for liver transplantation in HCC patients with large tumors. METHODS In this clinical study, 50 patients with HCC who were transplanted at our Liver Transplant Center between April 2006 and August 2019 and had tumors greater than 6 cm maximum diameter were retrospectively analyzed. Their survival and full clinical characteristics were examined, with respect to serum alpha-fetoprotein (AFP) and gamma glutamyl transpeptidase (GGT) levels. Kaplan-Meier survival estimates were used to determine overall survival and disease-free survival in these patients. The inclusion criterion was evidence of HCC. Exclusion criteria were the presence of macroscopic portal vein thrombosis or metastasis and a follow-up period of less than 90 d. RESULTS Using receiver operating characteristic curve (ROC) analysis, cutoff values of AFP 200 ng/mL and GGT 104 IU/L were identified and used in this study. Significantly longer overall survival (OS) and disease-free-survival (DFS) were found in patients who had lower values of either parameter, compared with higher values. Even greater differences in survival were found when the 2 parameters were combined. Two tumor size bands were identified, in searching for the limits of this approach with larger tumors, namely 6-10 cm and > 10 cm. Combination parameters in the 6-10 cm band reflected 5-year OS of 76.2% in patients with low AFP plus low GGT vs 0% for all other groups. Patients with tumors greater than 10 cm, did not have low AFP plus low GGT. The most consistent clinical correlates for longer survival were degree of tumor differentiation and absence of microscopic portal venous invasion. CONCLUSION Serum levels of AFP and GGT, both alone and combined, represent a simple prognostic identifier in patients with large HCCs undergoing liver transplant-ation.
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Affiliation(s)
- Volkan Ince
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Brian I Carr
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Harika Gozukara Bag
- Department of Biostatistics, Inonu University, School of Medicine, Malatya 44280, Turkey
| | - Veysel Ersan
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Sertac Usta
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Cemalettin Koc
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Fatih Gonultas
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Baris Kemal Sarici
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Serdar Karakas
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Koray Kutluturk
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Adil Baskiran
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
| | - Sezai Yilmaz
- Department of General Surgery, Inonu University, Liver Transplantation Institute, Malatya 44280, Turkey
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Liu KJ, Lv YX, Niu YM, Bu Y. Prognostic value of γ-glutamyl transpeptidase to albumin ratio combined with aspartate aminotransferase to lymphocyte ratio in patients with hepatocellular carcinoma after hepatectomy. Medicine (Baltimore) 2020; 99:e23339. [PMID: 33235099 PMCID: PMC7710195 DOI: 10.1097/md.0000000000023339] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.
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Affiliation(s)
- Ke-jun Liu
- School of Clinical Medicine, Ningxia Medical University
| | - Yong-xue Lv
- School of Basic Medicine, Ningxia Medical University
| | - Yi-ming Niu
- School of Clinical Medicine, Ningxia Medical University
| | - Yang Bu
- School of Clinical Medicine, Ningxia Medical University
- Department of Hepatobiliary Surgery, People‘s Hospital of Ningxia Hui Autonomous Region, Ningxia, China
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Zeng J, Zeng J, Wu Q, Lin K, Zeng J, Guo P, Zhou W, Liu J. Novel inflammation-based prognostic nomograms for individualized prediction in hepatocellular carcinoma after radical resection. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1061. [PMID: 33145280 PMCID: PMC7575986 DOI: 10.21037/atm-20-1919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background The prognosis for patients with hepatocellular carcinoma (HCC) after liver resection ranges widely and is unsatisfactory. This study aimed to develop two novel nomograms that combined tumor characteristics and inflammation-related indexes to predict overall survival (OS) and recurrence-free survival (RFS). Methods In total, 3,071 patients who underwent radical resection were recruited. Independent risk factors were identified by Cox regression analysis and used to conduct prognostic nomograms. The C-index, time-dependent areas under the receiver operating characteristic curve (time-dependent AUC), decision curve analysis (DCA), and calibration curves were used to assess the performance of the nomograms. Results Multivariate analysis revealed that alpha-fetoprotein (AFP), resection margin, neutrophil times γ-glutamyl transpeptidase-to-lymphocyte ratio (NrLR), platelet-to-lymphocyte ratio (PLR), γ-glutamyl transpeptidase-to-platelet ratio (GPR), tumor size, tumor number, microvascular invasion, and Edmondson-Steiner grade were the independent risk factors associated with OS. The independent risk factors associated with RFS were hepatitis, AFP, albumin-bilirubin (ALBI), NrLR, PLR, PNI, GPR, tumor size, tumor number, microvascular invasion, and Edmondson-Steiner grade. The C-index of the nomograms in the training and validation cohort were 0.71 [95% confidence interval (CI): 0.70–0.73] and 0.71 (95% CI: 0.69–0.74) for the OS, and 0.71 (95% CI: 0.70–0.73) and 0.74 (95% CI: 0.72–0.76) for RFS, respectively. The C-index, time-dependent AUC, and DCA of the nomograms showed significantly better predictive performances than those of commonly used staging systems. The models could stratify patients into three different risk groups. The web-based tools are convenient for clinical practice. Conclusions Two novel nomograms in which integrated inflammation-related indexes and accessible clinical parameters were developed to predict OS and RFS in HCC patients who underwent radical resection. Such models will help guide postoperative individualized follow-up and adjuvant therapy.
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Affiliation(s)
- Jianxing Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinhua Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China
| | - Qionglan Wu
- Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Kongying Lin
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Jianyang Zeng
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jingfeng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.,The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China
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Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma. DISEASE MARKERS 2020; 2020:4269460. [PMID: 32695241 PMCID: PMC7368954 DOI: 10.1155/2020/4269460] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 05/28/2020] [Accepted: 06/19/2020] [Indexed: 02/08/2023]
Abstract
Background Gamma-glutamyltransferase (GGT) is involved in tumor development and progression, but its prognostic value in α-fetoprotein- (AFP-) negative (AFP < 25 ng/mL) hepatocellular carcinoma (HCC) patients remains unknown. Methods A large cohort of 678 patients with AFP-negative HCC following curative resection who had complete data were enrolled in this study. The optimal cutoff value for the preoperative level of GGT was determined by the X-tile program. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were also identified. Results The optimal cutoff values for the preoperative levels of GGT were 37.2 U/L and 102.8 U/L, which were used to divide all patients into three subgroups (group 1, GGT < 37.2 U/L (n = 211, 31.1%); group 2, GGT ≥ 37.2 and <102.8 U/L (n = 320, 47.2%); group 3, GGT ≥ 102.8 U/L (n = 147, 21.7%)), with distinct OS times (58.5 vs. 53.5 vs. 44.4 months, P < 0.001) and DFS times (47.9 vs. 40.3 vs. 30.1 months, P < 0.001). Elevated preoperative GGT levels were associated with an unfavorable tumor burden (larger tumor size, multiple tumors, and microvascular invasion) and were selected as independent predictors of a worse OS (group 2 vs. group 1, HR: 1.73 (1.13-2.65), P = 0.011; group 3 vs. group 1, HR: 3.28 (2.10-5.13), P < 0.001) and DFS (group 2 vs. group 1, HR: 1.52 (1.13-2.05), P = 0.006; group 3 vs. group 1, HR: 2.11 (1.49-2.98), P < 0.001) in multivariable analysis. Conclusions Elevated preoperative GGT levels are associated with an unfavorable tumor burden and serve as an independent prognostic marker for worse outcomes in AFP-negative HCC patients following resection.
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Dai T, Deng M, Ye L, Liu R, Lin G, Chen X, Li H, Liu W, Yang Y, Chen G, Wang G. Prognostic value of combined preoperative gamma-glutamyl transpeptidase to platelet ratio and fibrinogen in patients with HBV-related hepatocellular carcinoma after hepatectomy. Am J Transl Res 2020; 12:2984-2997. [PMID: 32655824 PMCID: PMC7344083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 06/03/2020] [Indexed: 06/11/2023]
Abstract
The gamma-glutamyl transpeptidase to platelet ratio (GPR) has been reported as a non-invasive parameter for evaluating hepatic fibrosis and cirrhosis. However, only a few of studies investigated the relationship between GPR and liver cancer. Here, we sought to clarify the prognostic value of GPR as well as its combination with fibrinogen in patients with HBV-related hepatocellular carcinoma (HCC). We performed a retrospective study using data collected from 302 HCC patients, and evaluated the association between GPR, fibrinogen and clinicopathological characteristics using the chi-square test. Additionally, we assessed disease-free survival (DFS) and overall survival (OS) using the Kaplan-Meier method and log-rank test, then performed univariate and multivariate COX analyses to identify the prognostic factors. The prognostic performance of combined GPR and fibrinogen was evaluated by the receiver operating characteristic curve analysis. Results showed that GPR was associated with gender, history of smoking and drinking, cirrhosis, antiviral treatments, tumor number, and Child-Pugh grade. Univariate analysis revealed a significant correlation between tumor diameter, vascular invasion, BCLC stage, alpha-fetal protein, GPR, fibrinogen, and NLR with both DFS and OS in HCC patients. Only GPR and fibrinogen were found to be independently associated with both DFS and OS according to multivariate analysis. Furthermore, predictive capacity was enhanced by combining GPR with fibrinogen owing to a larger area under the curve than other indexes or models. Overall, preoperative GPR could be an effective non-invasive predictor for prognosis of HBV-related HCC patients, and a combination of GPR and fibrinogen improved the prognostic performance.
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Affiliation(s)
- Tianxing Dai
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Mingbin Deng
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Linsen Ye
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Rongqiang Liu
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Guozhen Lin
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Xiaolong Chen
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Guihua Chen
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen UniversityGuangzhou 510630, China
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplant Program, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, China
- Organ Transplantation Institute of Sun Yat-Sen UniversityGuangzhou 510630, China
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Ince V, Carr BI, Bag HG, Koc C, Usta S, Ersan V, Baskiran A, Sahin TT, Yilmaz S. Gamma glutamyl transpeptidase as a prognostic biomarker in hepatocellular cancer patients especially with >5 cm tumors, treated by liver transplantation. Int J Biol Markers 2020; 35:91-95. [PMID: 32436751 DOI: 10.1177/1724600820921869] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Serum AFP levels are typically elevated in less than 50% of hepatocellular cancer (HCC) patients. Gamma-glutamyl transpeptidase (GGT) levels have been suggested to be a potentially useful HCC biomarker. AIMS To assess in a cohort of prospectively evaluated HCC patients who underwent liver transplant and whose survival was known; the occurrence, prognosis, and clinical characteristics of patients with elevated serum GGT levels. RESULTS Serum GGT levels were found to be elevated in a higher proportion in patients with either small or large HCC than alpha-fetoprotein (AFP) levels, and were significantly related to prognosis in patients with large size HCCs. There was no clear correlation between GGT and AFP levels, likely reflecting different HCC characteristics or HCC cell lineages associated with these two markers. Furthermore, elevated GGT was found in 24% of low-AFP patients with small tumors and 46% with large tumors. Elevated GGT levels were also significantly associated with microvascular invasion and tumor diameter. CONCLUSIONS Elevated serum GGT levels were associated with HCC size and worse survival, and were unrelated to AFP levels. GGT may be a useful prognostic tumor marker, especially for low-AFP HCC patients.
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Affiliation(s)
- Volkan Ince
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Brian I Carr
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Harika Gozukara Bag
- Department of Biostatistics, Medical School, Inonu University, Malatya, Turkey
| | - Cemalettin Koc
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Sertac Usta
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Veysel Ersan
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Adil Baskiran
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Tevfik Tolga Sahin
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery, Liver Transplantation Institute, Inonu University, Malatya, Turkey
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CircPIP5K1A facilitates gastric cancer progression via miR-376c-3p/ZNF146 axis. Cancer Cell Int 2020; 20:81. [PMID: 32190005 PMCID: PMC7071687 DOI: 10.1186/s12935-020-1122-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 01/23/2020] [Indexed: 02/07/2023] Open
Abstract
Background Recently, many emerging circular RNAs (circRNAs) have been studied in human malignancies, including gastric cancer (GC). Researches concerning cancers have revealed that aberrant expression of circRNAs play a big part in tumorigenesis and development of diverse malignant tumors. Although hsa_circ_0014130 (circPIP5K1A) has been confirmed to be closely related to non-small cell lung cancer (NSCLC) progression, the knowledge of its function on GC progression remains unclear. Therefore, it is of great interest to uncover the underlying role of circPIP5K1A in GC. Methods The expression and characteristic of circPIP5K1A were separately analyzed by RT-qPCR, nucleic acid electrophoresis, RNase R and Actinomycin D treatment. CCK-8, colony formation, EdU, transwell, TUNEL, flow cytometry, luciferase reporter, RIP and RNA pull-down assays were employed to testify the regulatory role of circPIP5K1A in GC. Results In current study, circPIP5K1A, featured with closed-loop structure, was proved to be highly expressed in tissues and cells of GC. Loss-of-function assays depicted that silencing circPIP5K1A suppressed GC development. Follow-up mechanism tests unveiled that circPIP5K1A bound with miR-376c-3p and inhibition of miR-376c-3p reversed circPIP5K1A downregulation-mediated effect on GC progression. Additionally, ZNF146 was verified to be the downstream molecule of circPIP5K1A/miR-376c-3p axis in modulating GC progression. Conclusions circPIP5K1A stimulates GC progression by sponging miR-376c-3p to upregulate ZNF146 expression.
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Carr BI, Ince V, Bag HG, Ersan V, Usta S, Yilmaz S. Microscopic vascular invasion by hepatocellular carcinoma in liver transplant patients. CLINICAL PRACTICE (LONDON, ENGLAND) 2020; 17:1497-1505. [PMID: 33343877 PMCID: PMC7746034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
BACKGROUND A characteristic of Hepatocellular Carcinoma (HCC) is to invade the portal venous system in the liver as a means of spread within the liver and systemically. The ensuing Portal Vein Thrombosis (PVT) is a poor prognosis parameter and often diagnosed radiologically pre-treatment. More limited Microvascular Portal Invasion (microPVI) is typically diagnosed on examination of tumors removed after treatment by resection or transplant. The biological characteristics and subsets of PVI are incompletely characterized. AIMS To examine HCC patients with and without microPVI to understand the clinical relationships to other tumor and clinical characteristics and to survival. METHODS A cohort of 270 liver transplant patients with HCC without macroscopic PVT that were available to us was examined. Patients with (165) and without (105) microPVI were compared for survival and clinical features. RESULTS The mean survival of patients with and without microPVI was significantly different: 86.6 versus 110.5 months, p=0.007.The microPVI+ patients differed from microPVI- patients in having a significantly larger number of tumor nodules, tumor size and higher serum levels of both Alpha-Fetoprotein (AFP) and almost significant for higher Gamma-Glutamyl Transpeptidase (GGT, p=0.053). Survival in microPVI+ patients related significantly to serum GGT (p=0.006) but not to AFP levels. The incidence of microPVI increased with increase in tumor size and survival decreased significantly with increase in tumor size for microPVI patients. Increase in tumor size was also associated with significantly higher serum GGT levels in patients who were microPVI+, but not in those who were microPVI. Furthermore, patients with microPVI who had prolonged survival significantly differed from those with shorter survival in respect only to tumor size and serum GGT levels. CONCLUSION These findings draw attention to a group of patients with microPVI who have long survival and to the usefulness of serum GGT levels in their evaluation and prognosis.
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Affiliation(s)
- Brian I Carr
- Deptment of Surgery, Liver Transplantation Institute, Inonu University, Turkey
| | - Volkan Ince
- Deptment of Surgery, Liver Transplantation Institute, Inonu University, Turkey
| | | | - Veysel Ersan
- Deptment of Surgery, Liver Transplantation Institute, Inonu University, Turkey
| | - Sertac Usta
- Deptment of Surgery, Liver Transplantation Institute, Inonu University, Turkey
| | - Sezai Yilmaz
- Deptment of Surgery, Liver Transplantation Institute, Inonu University, Turkey
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He L, Li P, Jiang Y, Hu J, Ma J, Ye X, Yang J, Zhou Y, Liang X, Ai Z, Lin Y, Wei H. A new algorithm for predicting long-term survival in chronic hepatitis B patients with variceal bleeding after endoscopic therapy. Dig Liver Dis 2019; 51:1166-1171. [PMID: 30723020 DOI: 10.1016/j.dld.2019.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 01/03/2019] [Accepted: 01/04/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS A predictive algorithm for survival is urgently needed in clinical practice. This study aimed to establish an algorithm to predict long-term survival in chronic hepatitis B (CHB) patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy. METHODS This was a retrospective study in which 603 patients who followed-up for three years were randomly assigned into a training cohort and a validation cohort in a 2:1 ratio. A new score model was devised based on the result of Cox regression analysis in the training cohort, and was verified in the validation cohort. RESULTS A prediction score model composed of age, neutrophil-lymphocyte ratio, gamma-glutamyl transpeptidase and MELD score was established. The score ranged from 0 to 11. Areas under the ROC curve of the score were 0.821 (p < 0.001, 95% CI: 0.769-0.873) and 0.827 (p < 0.001, 95% CI: 0.753-0.900) in the training cohort and validation cohort, respectively. Scores 0-4 and 5-11 identified patients as low-risk and high-risk categories, respectively. The cumulative 3-year survival rate was significantly higher in the low-risk group than in the high-risk group (p < 0.001). CONCLUSION The new score model can be used to predict long-term survival in CHB patients with hepatic cirrhosis and variceal bleeding after endoscopic therapy.
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Affiliation(s)
- Lingling He
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ping Li
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yu Jiang
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Julong Hu
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jiali Ma
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaohui Ye
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Junru Yang
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuling Zhou
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiuxia Liang
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhenglin Ai
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yijun Lin
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongshan Wei
- Department of gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
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Liao M, Qin W, Liao Y, Yao R, Yu J, Liao W. Prognostic Value of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in Patients With Single Tumor Size ≤ 5 cm Hepatocellular Carcinoma After Radical Resection. Front Oncol 2019; 9:347. [PMID: 31165038 PMCID: PMC6536585 DOI: 10.3389/fonc.2019.00347] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 04/15/2019] [Indexed: 12/13/2022] Open
Abstract
Prediction of prognosis of hepatocellular carcinoma (HCC) has shown an important role in improving treatment outcomes and preventing disease progression, however, the prognostic indicator of HCC is still lacking. The purpose of this study is to investigate the predictive value of GLR (gamma-glutamyl transpeptidase to lymphocyte count ratio) in single HCC with a tumor size (TS) ≤ 5 cm. A retrospective analysis was performed on 272 patients with TS ≤ 5 cm who underwent radical resection. The Pearson χ2 test was applied to discuss the relationship between HCC and GLR, alpha-fetoprotein (AFP). Then univariate and multivariate analysis was utilized to predict the risk factors for survival prognosis in patients. In this study, GLR showed a positive relation with tumor size, tumor-node-metastasis (TNM) stage, microvascular invasion, early recurrence, and serum aspartate aminotransferase (AST) level, while the AFP value only correlated with drinking. Elevated GLR value had poor overall survival (OS) and progression-free survival (PFS) of TS ≤ 5 cm HCC patients, GLR level and tumor size were closely related to the prognosis of small HCC patients compared with AFP. GLR may serve as a prognostic marker for dynamic monitoring of HCC patients with single TS ≤ 5 cm after radical resection.
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Affiliation(s)
- Minjun Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China.,Oncology Medical College, Guangxi Medical University, Nanning, China
| | - Wanying Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yan Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China.,Disease Prevention and Control Center of Guilin, Guilin, China
| | - Renzhi Yao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Junxiong Yu
- Department of Anesthesiology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
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Sun P, Li Y, Chang L, Tian X. Prognostic and clinicopathological significance of Gamma-Glutamyltransferase in patients with hepatocellular carcinoma: A PRISMA-compliant meta-analysis. Medicine (Baltimore) 2019; 98:e15603. [PMID: 31083251 PMCID: PMC6531078 DOI: 10.1097/md.0000000000015603] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Many studies explored the prognostic and clinicopathological significance of pretreatment serum Gamma-Glutamyltransferase (GGT) level in hepatocellular carcinoma (HCC). However, there are inconsistent results in the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC. Thus, we conducted this meta-analysis to comprehensively assess the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC patients. METHODS We systematically searched PubMed, EMBASE and Web of Science for relevant studies (up to June 14, 2018). The estimated hazard ratios (HRs) were used to assess the association between pretreatment serum GGT level and survival in HCC patients. The estimated odds ratios (ORs) were applied to evaluate the correlation between pretreatment serum GGT and clinicopathological features in HCC. RESULTS Our results showed that high pretreatment serum GGT level was significantly correlated with poor overall survival (OS) (HR = 1.70, 95% CI: 1.54-1.87; P < .01) and disease-free survival/relapse-free survival (DFS/RFS) (HR = 1.56, 95% CI: 1.42-1.71; P < .01). Additionally, our results also revealed that there was a close correlation between GGT level and several clinicopathological features in HCC patients, including vascular invasion, tumor size, tumor number and Alpha-fetoprotein (AFP) level. CONCLUSIONS This meta-analysis shows that high pretreatment serum GGT level is significantly correlated with poor survival and unfavorable clinicopathological features in HCC patients, suggesting that pretreatment serum GGT may be an economical and effective prognostic biomarker for HCC patients. However, more high-quality studies are still warranted to further validate our findings, considering there are several limitations in this meta-analysis.
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Liu Y, Zhang Q, Yang X, Li Y, Zhu B, Niu S, Huang Y, Hu Y, Wang X. Effects of various interventions on the occurrence of macrovascular invasion of hepatocellular carcinoma after the baseline serum γ-glutamyltransferase stratification. Onco Targets Ther 2019; 12:1671-1679. [PMID: 30881022 PMCID: PMC6400138 DOI: 10.2147/ott.s184302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Elevated serum γ-glutamyltransferase (γ-GT) levels are related to an increased cancer risk and worse prognosis in many cancers. We evaluated the effects of γ-GT stratification on the occurrence of macrovascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) who underwent hepatic resection (HR), transcatheter arterial chemoembolization (TACE), or TACE combined with radiofrequency ablation (TACE-RFA). Patients and methods A total of 903 patients with HCC in Barcelona Clinic Liver Cancer Stage A or B were included. Of these patients, 118 underwent HR, 445 underwent TACE-RFA, 256 underwent TACE, and 84 patients received conservative treatment only (control group). γ-GT, albumin, α-fetoprotein, and intervention were selected as significant predictive factors for MVI in 1 year by forward selection. The optimal cutoff value of γ-GT was 39 IU/L according to receiver operating characteristic analysis, with a sensitivity and specificity of 87.0% and 45.6%, respectively. Results The 1-year MVI incidence of patients with HCC in the group with γ-GT ≥39 IU/L was higher than that of the group with γ-GT <39 IU/L treated with HR, TACE-RFA, or TACE (P=0.0166, P=0.0041, and P<0.001, respectively). The MVI rates at 1 year were similar in the group with γ-GT ≥39 IU/L that underwent HR, TACE-RFA, or TACE and the control group (P=0.4402, P=0.2214, and P=0.4159, respectively). Different effects of various treatments with γ-GT <39 IU/L group on the occurrence of MVI are not significant (P=0.5167). However, the incidence of MVI after TACE was significantly higher than that after HR or TACE-RFA in γ-GT ≥39 IU/L group (P=0.0253). Conclusion Baseline serum γ-GT stratification may help select the appropriate treatment to reduce the MVI incidence.
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Affiliation(s)
- Yao Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Xue Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Yuxin Li
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Bingbing Zhu
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of C Medicine, Beijing 100700, People's Republic of China
| | - Shuaishuai Niu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Yunyi Huang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of C Medicine, Beijing 100700, People's Republic of China
| | - Ying Hu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People's Republic of China,
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The prognostic significance of pretreatment serum γ-glutamyltranspeptidase in primary liver cancer: a meta-analysis and systematic review. Biosci Rep 2018; 38:BSR20181058. [PMID: 30389711 PMCID: PMC6259011 DOI: 10.1042/bsr20181058] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 10/17/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022] Open
Abstract
Aim: To assess the prognostic value of the pretreatment serum γ-glutamyltranspeptidase (GGT) level in patients with primary liver cancer (PLC). Methods: Relevant studies were systematically searched online on Web of Science, PubMed, and Embase databases published until 9 October 2018. The end points were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). Meta-analysis was conducted using hazard ratio (HR), and its 95% confidence interval (CI) as effect measure. Results: A total of 33 eligible studies with 9238 patients with PLC were included in this meta-analysis. The synthesized analysis showed that that higher serum GGT level was significantly related to poorer OS (HR: 1.79, 95% CI: 1.66–1.93, P<0.01), RFS (HR: 1.60, 95% CI: 1.46–1.77, P<0.01), and DFS (HR: 1.52, 95% CI: 1.33–1.73, P<0.01) of patients with PLC. Subgroup analyses demonstrated that the negative prognostic impact of higher serum GGT level on OS and RFS was still of significance regardless of ethnicity, pathological type, sample size, cut-off value, first-line treatment, and analysis type. Conclusion: The pretreatment serum GGT might be a predictive factor of poor prognosis for PLC patients.
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Hsa_circ_0000673 is down-regulated in gastric cancer and inhibits the proliferation and invasion of tumor cells by targetting miR-532-5p. Biosci Rep 2018; 38:BSR20180538. [PMID: 30061181 PMCID: PMC6146288 DOI: 10.1042/bsr20180538] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 07/13/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022] Open
Abstract
Circular RNAs (circRNAs), a new class of endogenous non-coding RNAs, have recently been known to play critical roles in various cellular biological processes, including tumorigenesis, in which they act as an miRNA sponge that regulates gene expression. Thus, revealing the functions of circRNAs in carcinogenesis and cancer development has been of great interest. However, their expression and functions in gastric cancer (GC) development are still largely unknown. Therefore, the present study aimed to identify novel deregulated circRNAs in GC and reveal their biological functions and molecular mechanisms in GC. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression levels of circRNAs in GC tissues, cell lines, and plasma. The MTT assay, colony formation assay, transwell assay, and tumor xenografts in vivo were used to evaluate the effects of circRNAs on the proliferation and invasion of GC. The abovementioned methods coupled with Western blotting were used to investigate the molecular mechanisms. The current study showed that hsa_circ_0000673 was significantly down-regulated in GC. Overexpression of hsa_circ_0000673 inhibited the proliferation and invasion of GC cells. In contrast, hsa_circ_0000673 down-regulation promoted the proliferation and invasion of GC cells. Further studies revealed that hsa_circ_0000673 targetted miR-532-5p and up-regulated the expression of RUNX3. The present study showed that hsa_circ_0000673 was decreased in GC and it exerted tumor-suppressing effects by targetting miR-532-5p and up-regulating RUNX3 expression level. Hsa_circ_0000673 may be a promising diagnosis biomarker and therapeutic target in GC.
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Ventura Y, Carr BI, Kori I, Guerra V, Shibolet O. Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization. World J Gastroenterol 2018; 24:1641-1649. [PMID: 29686471 PMCID: PMC5910547 DOI: 10.3748/wjg.v24.i15.1641] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 03/10/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate novel predictors of survival in hepatocellular carcinoma (HCC) patients following transarterial chemoembolization (TACE).
METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results (total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index (AgI). We used The Wilcoxon rank-sum (Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival.
RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56 (95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase (GGTP) had ORs of 1.01 (95%CI: 1.003-1.026, P < 0.017) and 0.99 (95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18 (95%CI: 1.108-4.310, P < 0.024). GGTP’s single unit change had a HR for mortality of 1.003 (95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26 (95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003 (95%CI: 1.001-1.004, P < 0.001).
CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.
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Affiliation(s)
- Yossi Ventura
- Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 62431, Israel
- Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
| | - Brian I Carr
- Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir 35340, Turkey
| | - Issac Kori
- Interventional Radiology, Division of Imaging Tel Aviv Medical Center, Tel-Aviv 62431, Israel
| | - Vito Guerra
- Department of Clinical Trials and Epidemiology, IRCCS de Bellis, Castellana Grotte 70013, Italy
| | - Oren Shibolet
- Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 62431, Israel
- Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
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Kornberg A, Witt U, Schernhammer M, Kornberg J, Ceyhan GO, Mueller K, Friess H, Thrum K. Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma. Sci Rep 2017; 7:14176. [PMID: 29074969 PMCID: PMC5658419 DOI: 10.1038/s41598-017-14430-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 10/10/2017] [Indexed: 02/06/2023] Open
Abstract
The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%; p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non- 18F-FDG-avid and 18F-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25; p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT.
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Affiliation(s)
- Arno Kornberg
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany.
| | - Ulrike Witt
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Martina Schernhammer
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Jennifer Kornberg
- Department of Anaesthesiology, Klinikum Großhadern, LMU, Munich, Germany
| | - Gueralp O Ceyhan
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | | | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
| | - Katharina Thrum
- Institute of Pathology, Helios Klinikum Berlin, Berlin, Germany
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Fu SJ, Chen J, Ji F, Ju WQ, Zhao Q, Chen MG, Guo ZY, Wu LW, Ma Y, Wang DP, Zhu XF, He XS. MiR-486-5p negatively regulates oncogenic NEK2 in hepatocellular carcinoma. Oncotarget 2017; 8:52948-52959. [PMID: 28881785 PMCID: PMC5581084 DOI: 10.18632/oncotarget.17635] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 03/10/2017] [Indexed: 02/06/2023] Open
Abstract
NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion. Consequently, patients exhibiting high NEK2 expression had poorer prognosis. This was corroborated by our multivariate analysis that showed NEK2 to be an independent prognostic factor for HCC patient survival. Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. Tumor xenograft data from Balb/c nude mice demonstrated that HCC cells with high NEK2 expression formed larger tumors than those with low NEK2 expression. Finally, we showed that miR-486-5p suppressed NEK2 by directly binding to its transcript 3′UTR. We also demonstrated an inverse relationship between miR-486-5p and NEK2 expression in HCC patients. These findings suggest miR-486-5p negatively regulates NEK2, which is a critical prognostic indicator of HCC patient survival after liver transplantation.
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Affiliation(s)
- Shun-Jun Fu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Jian Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Fei Ji
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Wei-Qiang Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Qiang Zhao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Mao-Gen Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Zhi-Yong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Lin-Wei Wu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Dong-Ping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Xiao-Feng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
| | - Xiao-Shun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China
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Marino IR, Carr BI. New Developments in Orthotopic Liver Transplant for Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2017; 15:1-6. [PMID: 28301991 DOI: 10.6002/ect.tond16.l2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The use of orthotopic liver transplant for hepatocellular carcinoma was a major advance, pioneered by Thomas E. Starzl as a way to circumvent the limitations imposed on the liver surgeon by the presence of cirrhosis and liver failure. Patients with a few small tumors, whatever their degree of liver damage, may expect prolonged survival (70% at 5 years). Patients with more advanced tumors have high recurrence rates and more limited survival, possibly due to immune suppression or pretransplant understaging of their tumors. Another possibility is that patients with micrometastases have a longer survival time, during which the metastases eventually become evident. Recent advances include the identification of patients using levels of tumor markers to allow more careful patient selection with better outcomes. The contributions of molecular signatures and the new, effective antiviral agents are possibly significant.
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44
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Zhou L, Liu S, Han M, Feng S, Liang J, Li Z, Li Y, Lu H, Liu T, Ma Y, Cheng J. MicroRNA-185 induces potent autophagy via AKT signaling in hepatocellular carcinoma. Tumour Biol 2017; 39:1010428317694313. [PMID: 28240051 DOI: 10.1177/1010428317694313] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Studies have demonstrated that microRNA 185 may be a promising therapeutic target in liver cancer. However, its role in hepatocellular carcinoma is largely unknown. In this study, the proliferation of human HepG2 cells was inhibited by transfection of microRNA 185 mimics. Cell-cycle analysis revealed arrest at the G0/G1 phase. Transfection of HepG2 cells with microRNA 185 mimics significantly induced apoptosis. These data confirmed microRNA 185 as a potent cancer suppressor. We demonstrated that microRNA 185 was a compelling inducer of autophagy, for the first time. When cell autophagy was inhibited by chloroquine or 3-methyladenine, microRNA 185 induced more cell apoptosis. MicroRNA 185 acted as a cancer suppressor by regulating AKT1 expression and phosphorylation. Dual-luciferase reporter assays indicated that microRNA 185 suppressed the expression of target genes including RHEB, RICTOR, and AKT1 by directly interacting with their 3'-untranslated regions. Binding site mutations eliminated microRNA 185 responsiveness. Our findings demonstrate a new role of microRNA 185 as a key regulator of hepatocellular carcinoma via autophagy by dysregulation of AKT1 pathway.
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Affiliation(s)
- Li Zhou
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
| | - Shunai Liu
- 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.,3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ming Han
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
| | - Shenghu Feng
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
| | - Jinqiu Liang
- 4 Division of Infectious Disease, Civil Aviation General Hospital, Beijing, China
| | - Zhongshu Li
- 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.,3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yaru Li
- 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.,3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hongping Lu
- 2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.,3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ting Liu
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
| | - Yanhua Ma
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
| | - Jun Cheng
- 1 Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.,2 Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.,3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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