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Yang J, Jiang H, Xie K, Bashir MR, Wan H, Huang J, Qin Y, Chen J, Lu Q, Song B. Profiling hepatocellular carcinoma aggressiveness with contrast-enhanced ultrasound and gadoxetate disodium-enhanced MRI: An intra-individual comparative study based on the Liver Imaging Reporting and Data System. Eur J Radiol 2022; 154:110397. [PMID: 35696735 DOI: 10.1016/j.ejrad.2022.110397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/23/2022] [Accepted: 06/03/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE Contrast-enhanced ultrasound (CEUS) and gadoxetate disodium-enhanced MRI (EOB-MRI) may synergize in profiling hepatocellular carcinoma (HCC) aggressiveness considering distinct imaging traits. This study aimed to intra-individually compare CEUS and EOB-MRI with Liver Imaging Reporting and Data System (LI-RADS) in assessing HCC aggressiveness. METHOD From January 2015 to November 2020, consecutive at-risk patients with surgically-confirmed HCC who underwent both preoperative CEUS and EOB-MRI examinations were retrospectively enrolled. Image analyses were conducted independently by two masked radiologists for CEUS and EOB-MRI, respectively. The diagnostic performance of each modality for macrovascular invasion against pathology was evaluated and compared with the McNemar's test, while Edmondson-Steiner grade and the presence of microvascular invasion (MVI) were compared between patients with and without LR-M features on each modality. RESULTS A total of 140 patients (mean age, 51.9 years ± 11.0; 116 men) were included. Inter-modality agreement was poor (κ = -0.087 ∼ 0.139) for major LI-RADS features and moderate (κ = 0.449) for overall LI-RADS categorization, and LR-TIV and LR-M were the top sources of inter-modality variations. Although CEUS demonstrated significantly higher specificity for diagnosing macrovascular invasion (96% vs. 89%, P =.02), LR-M features on EOB-MRI were more effective in identifying higher Edmondson-Steiner grades (P =.01) and MVI (P =.02). CONCLUSIONS Marked discrepancies were found between CEUS and EOB-MRI in evaluating LI-RADS features and categories. Whereas CEUS showed superior diagnostic specificity for macrovascular invasion, LR-M features on EOB-MRI provided more information regarding tumor grade and MVI status in HCC patients.
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Affiliation(s)
- Jie Yang
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Kunlin Xie
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Mustafa R Bashir
- Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA; Center for Advanced Magnetic Resonance in Medicine, Duke University Medical Center, Durham, NC 27705, USA; Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
| | - Haifeng Wan
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jiayan Huang
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yun Qin
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jie Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Qiang Lu
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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Gao F, Wei Y, Zhang T, Jiang H, Li Q, Yuan Y, Yao S, Ye Z, Wan S, Wei X, Nie L, Tang H, Song B. New Liver MR Imaging Hallmarks for Small Hepatocellular Carcinoma Screening and Diagnosing in High-Risk Patients. Front Oncol 2022; 12:812832. [PMID: 35356206 PMCID: PMC8959840 DOI: 10.3389/fonc.2022.812832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/10/2022] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE Early detection and diagnosis of hepatocellular carcinoma (HCC) is essential for prognosis; however, the imaging hallmarks for tumor detection and diagnosis has remained the same for years despite the use of many new immerging imaging methods. This study aimed to evaluate the detection performance of hepatic nodules in high risk patients using either hepatobiliary specific contrast (HBSC) agent or extracellular contrast agent (ECA), and further to compare the diagnostic performances for hepatocellular carcinoma (HCC) using different diagnostic criteria with the histopathological results as reference standard. METHODS This prospective study included 247 nodules in 222 patients (mean age, 53.32 ± 10.84 years; range, 22-79 years). The detection performance and imaging features of each nodule were evaluated in all MR sequences by three experienced abdominal radiologists. The detection performance of each nodule on all MR sequences were compared and further the diagnostic performance of various diagnostic criteria were evaluated. RESULTS For those patients who underwent ECA-MRI, the conventional imaging hallmark of "AP + PVP and/or DP" was recommended, as 60.19% diagnostic sensitivity, 80.95% specificity and 100% lesion detection rate. Additionally, for those patients who underwent HBSC-MRI, the diagnostic criteria of "DWI + HBP" was recommended. This diagnostic criteria demonstrated, both in all tumor size and for nodules ≤2 cm, higher sensitivity (93.07 and 90.16%, all p <0.05, respectively) and slightly lower specificity (64.71 and 87.50%, all p >0.05, respectively) than that of the European Association for the Study of the Liver (EASL) criteria. CONCLUSIONS Different abbreviated MR protocols were recommended for patients using either ECA or HBSC. These provided imaging settings demonstrated high lesion detection rate and diagnostic performance for HCC.
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Affiliation(s)
- Feifei Gao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Wei
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Tong Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Shan Yao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Zheng Ye
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Shang Wan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | | | - Lisha Nie
- MR Research China, GE Healthcare, Beijing, China
| | - Hehan Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Sanya People’s Hospital, Sanya, China
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Sial N, Rehman J, Saeed S, Ahmad M, Hameed Y, Atif M, Rehman A, Asif R, Ahmed H, Hussain M, Khan M, Ambreen A, Ambreen A. Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers. Biosci Rep 2022; 42:BSR20211783. [PMID: 34908119 PMCID: PMC8738869 DOI: 10.1042/bsr20211783] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/12/2021] [Accepted: 11/30/2021] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. OBJECTIVES Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. METHODS In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan-Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). RESULTS We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. CONCLUSION In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.
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Affiliation(s)
- Nuzhat Sial
- Department of Zoology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Jalil Ur Rehman
- Department of Eastern Medicine, Qarshi University, Lahore, Pakistan
- University College of Conventional Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Saba Saeed
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Mukhtiar Ahmad
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Yasir Hameed
- Department of Zoology, University of the Punjab, Lahore, Pakistan
| | - Muhammad Atif
- University College of Conventional Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Abdul Rehman
- Department of Eastern Medicine, Qarshi University, Lahore, Pakistan
| | - Rizwan Asif
- Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Hamad Ahmed
- Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Safdar Hussain
- Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Muhammad Rashid Khan
- University College of Eastern Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Atifa Ambreen
- Allied Department, The Sahara College, Narowal, Pakistan
| | - Ayesha Ambreen
- Allied Department, The Sahara College, Narowal, Pakistan
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Takahashi M, Takehara Y, Fujisaki K, Okuaki T, Fukuma Y, Tooyama N, Ichijo K, Amano T, Goshima S, Naganawa AS. Three Dimensional Ultra-short Echo Time MRI Can Depict Cholesterol Components of Gallstones Bright. Magn Reson Med Sci 2021; 20:359-370. [PMID: 33390560 PMCID: PMC8922345 DOI: 10.2463/mrms.mp.2020-0009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 09/10/2020] [Indexed: 11/21/2022] Open
Abstract
PURPOSE Non-calcified cholesterol stones that are small in size are hard to be depicted on CT or magnetic resonance cholangiopancreatography. This institutional review board (IRB)-approved retrospective in vitro study aims to characterize contrast behaviors of 3 main components of the gallstones, i.e., cholesterol component (CC), bilirubin calcium component (BC) and CaCO3 (CO) on 3D radial scan with ultrashort TE (UTE) MRI, and to test the capability of depicting CC of gallstones as bright signals as compared to background saline. METHODS Fourteen representative gallstones from 14 patients, including 15 CC, 6 BC and 4 CO, were enrolled. The gallstones underwent MRI including fat-saturated T1-weighted image (fs-T1WI) and UTE MRI with dual echoes. The contrast-to-noise ratio (CNR) and the chemical analysis for the 25 portions of the stones were compared. RESULTS BC was bright on fs-T1WI, which did not change dramatically on UTE MRI and the signal did not remain on UTE subtraction image between dual echoes. Whereas the CC was negative or faintly positive signal on fs-T1WI, bright signal on UTE MRI and the contrast remained even higher on the UTE subtraction, which reflected their short T2 values. Median CNRs and standard errors of the segments on each imaging were as follows: on fs-T1WI, -10.2 ± 4.2 for CC, 149.7 ± 27.6 for BC and 37.9 ± 14.3 for CO; on UTE MRI first echo, 16.7 ± 3.3 for CC, 74.9 ± 21.3 for BC and 17.7 ± 8.4 for CO; on UTE subtraction image, 30.2 ±2.0 for CC, -11.2 ± 5.4 for BC and 17.8 ± 10.7 for CO. Linear correlations between CNRs and cholesterol concentrations were observed on fs-T1WI with r = -0.885, (P < 0.0001), UTE MRI first echo r = -0.524 (P = 0.0072) and UTE subtraction with r = 0.598 (P = 0.0016). CONCLUSION UTE MRI and UTE subtraction can depict CC bright.
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Affiliation(s)
- Mamoru Takahashi
- Department of Radiology, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
| | - Yasuo Takehara
- Department of Fundamental Development for Advanced Low Invasive Diagnostic Imaging, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Kenji Fujisaki
- Seirei Medical Checkup Center, Hamamatsu, Shizuoka, Japan
| | | | | | - Norihiro Tooyama
- Department of Radiology, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
| | - Katsutoshi Ichijo
- Department of Radiology, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
| | - Tomoyasu Amano
- Department of Radiological Technology, Seirei Mikatahara General Hospital, Hamamatsu, Shizuoka, Japan
| | - Satoshi Goshima
- Department of Diagnostic Radiology & Nuclear Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - and Shinji Naganawa
- Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
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LncRNA ELF3-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2021; 2021:8323487. [PMID: 34336727 PMCID: PMC8286182 DOI: 10.1155/2021/8323487] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/26/2021] [Accepted: 07/03/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Expression of long noncoding RNA (lncRNA) ELF3 antisense RNA 1 (ELF3-AS1) is observed in some cancers, while its role in hepatocellular carcinoma (HCC) is unclear. The study aimed to investigate the relationship between ELF3-AS1 and HCC based on database, bioinformatics, and statistical analysis. METHODS In this study, Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, gene set enrichment analysis (GSEA), and immunoinfiltration analysis were used to assess the relationship between ELF3-AS1 expression and clinical characteristics of HCC patients, the relationship between ELF3-AS1 expression and prognosis of HCC patients, and the possible functions of ELF3-AS1 in HCC. RESULTS High expression of ELF3-AS1 in patients with HCC was related to T stage (P < 0.001), gender (P = 0.006), residual tumor (P = 0.008), histologic grade (P < 0.001), adjacent hepatic tissue inflammation (P = 0.011), AFP (P < 0.001), and vascular invasion (P = 0.028). High ELF3-AS1 expression was associated with poor overall survival (OS) (P = 0.001) and DSS (P = 0.047). ELF3-AS1 expression (P = 0.011) was independently correlated with OS in HCC patients. In the high ELF3-AS1 expression group, GPCR-radioligand binding, M phase, Class A/1 (rhodopsin-like receptors), cell cycle checkpoints, translation, mitotic metaphase and anaphase, signaling by robo receptors, keratinization, and rRNA processing were differentially enriched by GESA. ELF3-AS1 expression was associated with immune infiltrating cells. CONCLUSIONS ELF3-AS1 expression was associated with poor prognosis in HCC. ELF3-AS1 expression was significantly associated with immune infiltration. ELF3-AS1 is a promising biomarker that can be used for the diagnosis and prognosis of HCC.
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Qin Y, Cheng S, Li Y, Zou S, Chen M, Zhu D, Gao S, Wu H, Zhu L, Zhu X. The development of a Glypican-3-specific binding peptide using in vivo and in vitro two-step phage display screening for the PET imaging of hepatocellular carcinoma. Biomater Sci 2021; 8:5656-5665. [PMID: 32896851 DOI: 10.1039/d0bm00943a] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Glypican-3 (GPC3) is a diagnostic biomarker for hepatocellular carcinoma (HCC). Although numerous designs targeting GPC3 have been reported, the HCC diagnostic agents with specific tumor accumulation and low background, particularly in normal liver tissue, are still in need. Peptides have attracted considerable attention as an imaging probe due to their low immunogenicity, short in vivo circulation time, and acceptable production cost. Herein, a two-step phage display screening approach was performed against GPC3-high expression tumor xenografts in vivo, followed by human recombinant GPC3 protein in vitro. A GPC3-specific binding peptide, named TJ12P2, with the sequence of Ser-Asn-Asp-Arg-Pro-Pro-Asn-Ile-Leu-Gln-Lys-Arg (SNDRPPNILQKR) was identified. The apparent Kd value between TJ12P2 and the GPC3 protein was measured as 158.2 ± 26.25 nM. After 18F labeling, 18F-AlF-NOTA-TJ12P2 was found accumulated in the tumors by positron emission tomography (PET) imaging in two HCC subcutaneous tumor models (HepG2 and SMMC-7721) with high GPC3 expression. Static PET imaging revealed that 18F-AlF-NOTA-TJ12P2 accumulation in the HepG2 and SMMC-7721 tumors reached 1.825 ± 0.296 %ID g-1 and 1.575 ± 0.520 %ID g-1, with tumor-to-muscle ratios of 4.14 ± 0.50 and 4.25 ± 0.25, respectively, at 30 min post-injection (p.i.). Much less accumulation (0.533 ± 0.078 %ID g-1) of the 18F-AlF-NOTA-TJ12P2 was found in the control PC3 tumors with low GPC3 expression. More importantly, no obvious normal liver uptake of TJ12P2 was observed in the abovementioned animal models. As a result, a novel peptide targeting GPC3, TJ12P2, with strong affinity and specificity was identified using a two-step phage display screening technique in the present study. The 18F-AlF-NOTA-TJ12P2 may be a promising PET imaging probe with translational potential for accurate HCC diagnosis.
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Affiliation(s)
- Yushuang Qin
- Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Siyuan Cheng
- Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Yesen Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Sijuan Zou
- Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Minglong Chen
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Dongling Zhu
- Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Shi Gao
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Hua Wu
- Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Lei Zhu
- Departments of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
| | - Xiaohua Zhu
- Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
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Zhang N, Xu H, Ren AH, Zhang Q, Yang DW, Ba T, Wang ZC, Yang ZH. Does Training in LI-RADS Version 2018 Improve Readers' Agreement with the Expert Consensus and Inter-reader Agreement in MRI Interpretation? J Magn Reson Imaging 2021; 54:1922-1934. [PMID: 33963801 DOI: 10.1002/jmri.27688] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND The Liver Imaging Reporting and Data System (LI-RADS) was established for noninvasive diagnosis for hepatocellular carcinoma (HCC). However, whether training can improve readers' agreement with the expert consensus and inter-reader agreement for final categories is still unclear. PURPOSE To explore training effectiveness on readers' agreement with the expert consensus and inter-reader agreement. STUDY TYPE Prospective. SUBJECTS Seventy lesions in 61 patients at risk of HCC undergoing liver MRI; 20 visiting scholars. FIELD STRENGTH/SEQUENCE 1.5 T or 3 T, Dual-echo T1 WI, Fast spin-echo T2 WI, SE-EPI DWI, and Dynamic multiphase fast gradient-echo T1 WI. ASSESSMENT Seventy lesions assigned LI-RADS categories of LR1-LR5, LR-M, and LR-TIV by three radiologists in consensus were randomly selected, with 10 cases for each category. The consensus opinion was the standard reference. The third radiologist delivered the training. Twenty readers reviewed images independently and assigned each an LI-RADS category both before and after the training. STATISTICAL TESTS Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, receiver operating characteristic (ROC) analysis, simple and weighted kappa statistics, and Fleiss kappa statistics. RESULTS Before and after training: readers' AUC (areas under ROC) for LR-1-LR-5, LR-M, and LR-TIV were 0.898 vs. 0.913, 0.711 vs. 0.876, 0.747 vs. 0.860, 0.724 vs. 0.815, 0.844 vs. 0.895, 0.688 vs. 0.873, and 0.720 vs. 0.948, respectively, and all improved significantly (P < 0.05), except LR-1(P = 0.25). Inter-reader agreement between readers for LR-1-LR-5, LR-M, LR-TIV were 0.725 vs. 0.751, 0.325 vs. 0.607, 0.330 vs. 0.559, 0.284 vs. 0.488, 0.447 vs. 0.648, 0.229 vs. 0.589, and 0.362 vs. 0.852, respectively, and all increased significantly (P < 0.05). For training effectiveness on both AUC and inter-reader agreement, LR-TIV, LR-M, and LR-2 improved most, and LR-1 made the least. DATA CONCLUSION This study shows LI-RADS training could improve reader agreement with the expert consensus and inter-reader agreement for final categories. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Nan Zhang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Hui Xu
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
| | - A-Hong Ren
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Qian Zhang
- National Clinical Research Center of Digestive Diseases, Beijing, China.,Clinical Epidemiology and EBM Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Da-Wei Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Te Ba
- Department of Radiology, First Hospital of Fangshan District, Beijing, China
| | - Zhen-Chang Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Zheng-Han Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Center of Digestive Diseases, Beijing, China
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8
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Xu H, Tang Y, Zhao Y, Wang F, Gao X, Deng D, Gu Y. SPECT Imaging of Hepatocellular Carcinoma Detection by the GPC3 Receptor. Mol Pharm 2021; 18:2082-2090. [PMID: 33797932 DOI: 10.1021/acs.molpharmaceut.1c00060] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The glypican-3 (GPC3) receptor is a membrane protein that is highly expressed in tumor tissues but rarely expressed in the normal liver and can be used as a target for early diagnosis of hepatocellular carcinoma (HCC). Herein, we developed a GPC3-targeted 99mTc-labeled probe for SPECT imaging in HCC. 99mTc-HPG was rapidly radiosynthesized within 20 min with an excellent radiochemical purity (>98%), possessing good stability. Results from in vitro cell binding assays indicated that the binding specificity of 99mTc-HPG to GPC3-positive HepG2 cells was acceptable. For SPECT/CT imaging, the HepG2 tumors were clearly visualized with the highest tumor/muscle ratio (11.55 ± 0.54) at 1 h post-injection, and the tumor uptake of 99mTc-HPG reduced from 2.99 ± 0.15 to 1.17 ± 0.09% ID/g in the blocking study. Convenient preparation, excellent GPC3 specificity in HCC, rapid clearance from normal organs, and good biosafety profiles of 99mTc-HPG warrant further investigations for clinical translation.
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Affiliation(s)
- Haoran Xu
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Yongjia Tang
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Yue Zhao
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Fang Wang
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Xin Gao
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Dawei Deng
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
| | - Yueqing Gu
- State Key Laboratory of Natural Medicine, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, No. 24 Tongjia Lane, Gulou District, Nanjing 211198, China
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9
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Integrated bioinformatics analysis identified MTHFD1L as a potential biomarker and correlated with immune infiltrates in hepatocellular carcinoma. Biosci Rep 2021; 41:227681. [PMID: 33605411 PMCID: PMC7897918 DOI: 10.1042/bsr20202063] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 01/20/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022] Open
Abstract
Liver hepatocellular carcinoma (LIHC) is one of the most frequently occurring primary malignant liver tumors and seriously harms people’s health in the world. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) has been shown to be associated with colon cancer cell proliferation, colony formation and invasion. In the present study, a total of 370 LIHC and 51 normal samples data were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatics and immunohistochemistry (IHC) analysis showed that MTHFD1L is highly expressed in liver tumors. Correlation analysis suggested the differences of vital status between high- and low-expression MTHFD1L groups of LIHC. Univariate and multivariate Cox proportional hazards regression were performed to identify the relationship between clinical characteristics and overall survival (OS). In addition, to explore whether MTHFD1L has an effect on the immune infiltration of LIHC. The correlation between MTHFD1L expression and 24 immune cells were analyzed by ImmuneCellAI database. Furthermore, we combined three databases CIBERSORT, TIMER and ImmuneCellAI to do a comprehensive validation and determined that dendritic cells (DCs) resting, macrophage M0 and macrophage M2 closely related to the expression of MTHFD1L. The results showed that MTHFD1L was a potential prognostic biomarker for LIHC, and could help to elucidate that how the immune microenvironment promotes liver cancer development.
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Kovac JD, Ivanovic A, Milovanovic T, Micev M, Alessandrino F, Gore RM. An overview of hepatocellular carcinoma with atypical enhancement pattern: spectrum of magnetic resonance imaging findings with pathologic correlation. Radiol Oncol 2021; 55:130-143. [PMID: 33544992 PMCID: PMC8042819 DOI: 10.2478/raon-2021-0004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 12/15/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the setting of cirrhotic liver, the diagnosis of hepatocellular carcinoma (HCC) is straightforward when typical imaging findings consisting of arterial hypervascularity followed by portal-venous washout are present in nodules larger than 1 cm. However, due to the complexity of hepatocarcinogenesis, not all HCCs present with typical vascular behaviour. Atypical forms such as hypervascular HCC without washout, isovascular or even hypovascular HCC can pose diagnostic dilemmas. In such cases, it is important to consider also the appearance of the nodules on diffusion-weighted imaging and hepatobiliary phase. In this regard, diffusion restriction and hypointensity on hepatobiliary phase are suggestive of malignancy. If both findings are present in hypervascular lesion without washout, or even in iso- or hypovascular lesion in cirrhotic liver, HCC should be considered. Moreover, other ancillary imaging findings such as the presence of the capsule, fat content, signal intensity on T2-weighted image favour the diagnosis of HCC. Another form of atypical HCCs are lesions which show hyperintensity on hepatobiliary phase. Therefore, the aim of the present study was to provide an overview of HCCs with atypical enhancement pattern, and focus on their magnetic resonance imaging (MRI) features. CONCLUSIONS In order to correctly characterize atypical HCC lesions in cirrhotic liver it is important to consider not only vascular behaviour of the nodule, but also ancillary MRI features, such as diffusion restriction, hepatobiliary phase hypointensity, and T2-weighted hyperintensity. Fat content, corona enhancement, mosaic architecture are other MRI feautures which favour the diagnosis of HCC even in the absence of typical vascular profile.
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Affiliation(s)
- Jelena Djokic Kovac
- Center for Radiology and MRI, Clinical Center Serbia, School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Aleksandar Ivanovic
- Center for Radiology and MRI, Clinical Center Serbia, School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Marjan Micev
- Departament of Digestive Pathology, Clinical Center of Serbia, Belgrade, Serbia
| | - Francesco Alessandrino
- Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Richard M. Gore
- Department of Gastrointestinal Radiology, NorthShore University, Evanston, Pritzker School of Medicine at the University of Chicago, ChicagoUSA
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Ye Z, Zeng Z, Shen Y, Chen Z. Identification of hub genes in peripheral blood mononuclear cells for the diagnosis of hepatocellular carcinoma using a weighted gene co-expression network analysis. Exp Ther Med 2020; 20:890-900. [PMID: 32742331 PMCID: PMC7388247 DOI: 10.3892/etm.2020.8736] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 07/29/2019] [Indexed: 02/06/2023] Open
Abstract
Human hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive tract that is prevalent worldwide. Improving diagnosis methods for HCC helps to improve patient survival rate. The present study aimed to identify novel HCC biomarkers for the diagnosis of HCC through analyzing gene changes on peripheral blood mononuclear cells (PBMCs) and verifying these in additional samples. The gene expression profiles GSE49515 (including 10 specimens from normal patients and 10 specimens from patients with HCC) and GSE58208 (including 5 specimens from normal patients and 10 specimens from patients with HCC) were downloaded from the online Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) in PBMCs between healthy controls and patients with HCC were identified using R software. A total of 935 DEGs, including 686 upregulated DEGs and 249 downregulated DEGs, were identified in the present study. In order to identify any internal associations, these DEGs were used to construct weighted gene co-expression networks (WGCNA). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of genes in each module were conducted using the online database DAVID. Furthermore, hub genes with high module membership were identified in a co-expression network and receiver operating characteristic curves were used to verify the diagnostic values of these eight hub genes. Furthermore, the expression and diagnosis value of the eight hub genes were also verified in additional samples. The results of the present study suggested that secreted protein acidic and cysteine rich(SPARC), transmembrane protein 40 (TMEM40), solute carrier family 25 member 44, formyl peptide receptor 2 (FPR2), complement C8 β chain, N-myristoyltransferase 1, protein kinase C δ(PRKCD) and protein phosphatase, Mg2+/Mn2+ dependent 1M(PPM1M) were hub genes. SPARC, TMEM40, FPR2, PRKCD and PPM1M had prominent diagnostic value according to the results from the GEO data and the additional samples. The present study demonstrated that these hub genes may help to improve the diagnosis of HCC.
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Affiliation(s)
- Zi Ye
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Zhirui Zeng
- Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China.,Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China
| | - Yiyi Shen
- Department of Liver-Biliary Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China
| | - Zubing Chen
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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12
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Interobserver Agreement of Magnetic Resonance Imaging of Liver Imaging Reporting and Data System Version 2018. J Comput Assist Tomogr 2020; 44:118-123. [PMID: 31939892 DOI: 10.1097/rct.0000000000000945] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM This study aimed to assess the interobserver agreement of magnetic resonance (MR) imaging of Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018). SUBJECTS AND METHODS Retrospective analysis was done for 119 consecutive patients (77 male and 42 female) at risk of hepatocellular carcinoma who underwent dynamic contrast MR imaging. Image analysis was done by 2 independent and blinded readers for arterial phase hyperenhancement, washout appearance, enhancing capsule appearance, and size. Hepatic lesions were classified into 7 groups according to LI-RADS v2018. RESULTS There was excellent interobserver agreement of both reviewers for LR version 4 (κ = 0.887, P = 0.001) with 90.76% agreement. There was excellent interobserver agreement for nonrim arterial phase hyperenhancement (κ = 0.948; 95% confidence interval [CI], 0.89-0.99; P = 0.001), washout appearance (κ = 0.949; 95% CI, 0.89-1.0; P = 0.001); and enhancing capsule (κ = 0.848; 95% CI, 0.73-0.97; P = 0.001) and excellent reliability of size (interclass correlation, 0.99; P = 0.001). There was excellent interobserver agreement for LR-1 (κ = 1.00, P = 0.001), LR-2 (κ = 0.94, P = 0.001), LR-5 (κ = 0.839, P = 0.001), LR-M (κ = 1.00, P = 0.001), and LR-TIV (κ = 1.00; 95% CI, 1.0-1.0; P = 0.001), and good agreement for LR-3 (κ = 0.61, P = 0.001) and LR-4 (κ = 0.61, P = 0.001). CONCLUSION MR imaging of LI-RADS v2018 is a reliable imaging modality and reporting system that may be used for standard interpretation of hepatic focal lesions.
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Kornberg A, Witt U, Schernhammer M, Kornberg J, Müller K, Friess H, Thrum K. The role of preoperative albumin-bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma. J Surg Oncol 2019; 120:1126-1136. [PMID: 31578753 DOI: 10.1002/jso.25721] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 09/21/2019] [Indexed: 01/03/2025]
Abstract
BACKGROUND AND OBJECTIVES Albumin-bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC. METHODS Pre-LT available independent predictors of recurrence-free survival (RFS) and microvascular tumor invasion (MVI) were determined in 123 patients with HCC. RESULTS Posttransplant HCC recurrence rates were 10.5%, 15.9%, and 68.2% in ALBI grade 1, 2, and 3, respectively (P < .001). Along with serum α-fetoprotein (AFP) and C-reactive protein (CRP) levels, ALBI grades 1 or 2 was identified as an independent predictor of RFS (hazard ratio, 3.52; 95% confidence interval [CI], 1.577-7.842; P = .002). Furthermore, ALBI grade 3 proved to be the strongest indicator of MVI (odds ratio, 11.59; 95% CI, 3.412-39.381; P < .001). A novel oncological risk score-based on AFP, CRP, and ALBI grade provided the best discriminative capacity (c-statistic 0.806) in selecting liver recipients with low oncological risk profile. CONCLUSION Preoperative ALBI grade seems to be valuable for refinement of oncological risk stratification at LT for HCC.
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Affiliation(s)
- Arno Kornberg
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Ulrike Witt
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Martina Schernhammer
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Jennifer Kornberg
- Department of Anaesthesiology, Klinikum Großhadern, Ludwig-Maximilian-University of Munich, Munich, Germany
| | - Katharina Müller
- Department of Surgery, Friedrich-Schiller-University of Jena, Jena, Germany
| | - Helmut Friess
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Katharina Thrum
- Department of Pathology, Helios Klinikum Berlin, Berlin, Germany
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Hu P, Cui H, Lei T, Li S, Mai E, Jia F. Linc00511 Indicates A Poor Prognosis Of Liver Hepatocellular Carcinoma. Onco Targets Ther 2019; 12:9367-9376. [PMID: 31807017 PMCID: PMC6850899 DOI: 10.2147/ott.s228231] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/18/2019] [Indexed: 12/24/2022] Open
Abstract
Objective To uncover the specific function of linc00511 in the progression of liver hepatocellular carcinoma (LIHC) and the underlying mechanism. Patients and methods GEPIA dataset containing 9736 LIHC samples and 857 normal samples were downloaded from TCGA. Expression pattern and prognostic potential of linc00511 in LIHC were analyzed. Subsequently, expression level of linc00511 in LIHC tissues collected in our hospital and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Differential expressions of linc00511 in LIHC with different tumor grades and metastatic status were compared. After transfection of si-linc00511, proliferative and migratory changes in Huh7 and Hep3B cells were assessed by cell counting kit-8 (CCK-8), 5-ethynyl-2ʹ-deoxyuridine (EdU) and Transwell assay. Lastly, Pearson correlation analysis and qRT-PCR were conducted to investigate the interaction between linc00511 and miR-29c. Results Linc00511 was upregulated in LIHC tissues and cell lines. Its level was positively correlated to TNM staging, lymphatic metastasis and poor prognosis in LIHC patients. Knockdown of linc00511 attenuated proliferative and migratory abilities in Huh7 and Hep3B cells. In addition, miR-29c was downregulated in LIHC and negatively linked to linc00511 level. A negative interaction between linc00511 and miR-29c could be a regulatory feedback influencing the progression of LIHC. Conclusion Linc00511 accelerates the proliferation and migration in LIHC, thus aggravating tumor progression. Meanwhile, linc00511 could be utilized as a hallmark predicting poor prognosis in LIHC patients.
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Affiliation(s)
- Pingan Hu
- Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China
| | - Huxiao Cui
- Department of Hepatobiliary Surgery, Xuchang Central Hospital, Xuchang, People's Republic of China
| | - Ting Lei
- Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China
| | - Siqiao Li
- Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China
| | - Erhui Mai
- Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China
| | - Fuxin Jia
- Department of Hepatobiliary Surgery, Luoyang Center Hospital, Luoyang, People's Republic of China
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Lu RC, She B, Gao WT, Ji YH, Xu DD, Wang QS, Wang SB. Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol 2019; 25:4682-4695. [PMID: 31528094 PMCID: PMC6718031 DOI: 10.3748/wjg.v25.i32.4682] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/30/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. Various imaging modalities provide important information about HCC for its clinical management. Since positron-emission tomography (PET) or PET-computed tomography was introduced to the oncologic setting, it has played crucial roles in detecting, distinguishing, accurately staging, and evaluating local, residual, and recurrent HCC. PET imaging visualizes tissue metabolic information that is closely associated with treatment. Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis. The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance. The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.
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Affiliation(s)
- Ren-Cai Lu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Bo She
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Wen-Tao Gao
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Yun-Hai Ji
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Dong-Dong Xu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Quan-Shi Wang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Shao-Bo Wang
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
- Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China
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Qiao GL, Chen L, Jiang WH, Yang C, Yang CM, Song LN, Chen Y, Yan HL, Ma LJ. Hsa_circ_0003998 may be used as a new biomarker for the diagnosis and prognosis of hepatocellular carcinoma. Onco Targets Ther 2019; 12:5849-5860. [PMID: 31410028 PMCID: PMC6650091 DOI: 10.2147/ott.s210363] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 06/23/2019] [Indexed: 12/24/2022] Open
Abstract
Background Circular RNAs (circRNAs) play important roles in the progression of cancers, but the precise role of circRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC) remains to be clarified. The aim of the current study was to explore the diagnostic and prognostic values of hsa_circ_0003998 in HCC. Methods CircRNAs expression was measured using RNA-seq analysis from HCC tissues (n=6) (three cases with or without portal vein invasion). Hsa_circ_0003998 in 200 pairs of HCC and adjacent noncancerous tissues and HCC cell lines was examined using qRT-PCR and the clinicopathologic significance was determined. We also detected the plasma levels of hsa_circ_0003998 in HCC, hepatitis B patients and healthy controls. The clinical diagnosis and prognostic values were further determined using receiver operating characteristic (ROC) curve, Kaplan–Meier curve and Cox regression. Results Hsa_circ_0003998 was upregulated in HCC tissues (P<0.001) and HCC cell lines (HepG2, HuH7, MHCC97H) (P<0.001). In addition, upregulation of hsa_circ_0003998 level was associated with higher serum alpha-fetoprotien (AFP) level (P=0.003), larger tumor diameter (P=0.009), lower differentiation level (P=0.023) and microvascular invasion (P=0.028). The plasma level of hsa_circ_0003998 in HCC patients was significantly higher than those in hepatitis B patients (P<0.001) and healthy controls (P<0.001). Its level was significantly reduced after the operation (P<0.001). The area under the ROC curve (AUC) for distinguishing HCC from adjacent noncancerous tissues was 0.894 (95% CI=0.86–0.922, P<0.001), the sensitivity and specificity were 0.84 and 0.8, respectively. Comparing with hepatitis B patients and healthy controls, hsa_circ_0003998, respectively, had an AUC value of 0.833 (95% CI=0.763–0.889, P<0.001) and 0.892 (95% CI=0.831–0.937, P<0.001). Their sensitivity and specificity were 0.83, 0.7 and 0.8, 0.84, respectively. Moreover, the combination of hsa_circ_0003998 and AFP showed the highest AUC value of 0.947, the sensitivity and specificity were 0.88 and 0.92, respectively. The hsa_circ_0003998 (P=0.003) and AFP (P=0.008) levels were independent prognostic factors for HCC. The overall survival of HCC patients with high level of hsa_circ_0003998 was significantly poorer than those with low level (P=0.005). Conclusion Our findings suggest that hsa_circ_0003998 may be used as a novel potential biomarker for the diagnosis and prognosis of HCC patients.
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Affiliation(s)
- Guang-Lei Qiao
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Li Chen
- Department of Emergency Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China
| | - Wei-Hua Jiang
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Cheng Yang
- Department of Special Treatment, Third Affiliated Hospital of Second Military Medical University, Shanghai, People's Republic of China
| | - Chun-Mei Yang
- Department of Clinical Laboratory Diagnostics, Bei Hua University School, Jilin, People's Republic of China
| | - Li-Na Song
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Ying Chen
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Hong-Li Yan
- Department of Laboratory Diagnosis, and Reproductive Medicine Center, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Li-Jun Ma
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
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Inhibition of PSMD4 blocks the tumorigenesis of hepatocellular carcinoma. Gene 2019; 702:66-74. [DOI: 10.1016/j.gene.2019.03.063] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 03/14/2019] [Accepted: 03/27/2019] [Indexed: 02/07/2023]
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Guo D, Li Y, Chen Y, Zhang D, Wang X, Lu G, Ren M, Lu X, He S. DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway. Cell Prolif 2019; 52:e12628. [PMID: 31038266 PMCID: PMC6668976 DOI: 10.1111/cpr.12628] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 03/20/2019] [Accepted: 04/03/2019] [Indexed: 12/12/2022] Open
Abstract
Objectives This research aims to verify that the long non‐coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC. Materials and methods Firstly, qRT‐PCR was used to detect the expression of genes including LncRNA DANCR and miR‐27a‐3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual‐luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh‐NC and sh‐DANCR to detect proliferation and SMMC‐7721 cells stably transfected with sh‐NC and sh‐DANCR to investigate metastasis. Results The results of qRT‐PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh‐DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR‐27a‐3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR‐27a‐3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR‐27a‐3p axis regulates EMT progression by cell immunofluorescence and Western blot. Conclusions In a word, DANCR promotes HCC development and induces EMT by decoying miR‐27a‐3p to regulate ROCK1/LIMK1/COFILIN1 pathway.
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Affiliation(s)
- Dan Guo
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yarui Li
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yifei Chen
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Dan Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xin Wang
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Guifang Lu
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Mudan Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xinlan Lu
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shuixiang He
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Pickhardt PJ. Gastrointestinal Imaging: Rapid Advancements Leading to Improved Patient Care. Gastroenterol Clin North Am 2018; 47:xv-xvii. [PMID: 30115446 DOI: 10.1016/j.gtc.2018.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Affiliation(s)
- Perry J Pickhardt
- Abdominal Imaging Section, Department of Radiology, University of Wisconsin School of Medicine & Public Health, 600 Highland Avenue, Madison, WI 53792, USA.
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