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Diagnostics
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Clinicopathology and Prognosis of Hepatocellular Carcinoma
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Clinicopathology and Prognosis of Hepatocellular Carcinoma

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 8600

Special Issue Editor

Prof. Dr. Chien-Wei Su

E-Mail Website
Guest Editor
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Interests: hepatocellular carcinoma; hepatitis B virus; hepatitis D virus; systemic therapy; local ablation therapy

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death among males, and the sixth among females. The major risk factors for HCC are chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcoholism, and metabolic-dysfunction-associated fatty liver disease (MAFLD). Despite the successful implementation of HBV vaccination and extensive prescription of potent antiviral therapy for HBV or HCV infections, HCC incidence and mortality rates are still rising worldwide.

Moreover, HCC is a highly heterogenous cancer with different morphological and molecular phenotypes, clinical manifestations, responses to therapy, and outcomes. The risk of recurrence after curative therapy (e.g., resection or local ablation therapy) is still high in HCC patients.

To improve the outcomes of patients with HCC, it is necessary to elucidate hepatic carcinogenesis, identify prognostic factors, and determine adequate treatment modalities that are tailored to different clinical settings. The aim of this Special Issue is to publish high-quality research on the pathology, molecular diagnosis, clinical manifestations, staging, treatments, outcomes, as well as prevention of HCC. Original research, meta-analysis and review articles are welcome.

Prof. Dr. Chien-Wei Su
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatocellular carcinoma
  • prognosis
  • diagnosis
  • staging
  • therapy
  • prevention
  • pathology
  • biological marker

Published Papers (4 papers)

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Research

13 pages, 1769 KiB  
Article
Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma
by Ji Won Han, Ji Hoon Kim, Dong Hyun Kim, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Jaegyoon Ahn, Hyun Yang and Pil Soo Sung
Diagnostics 2023, 13(8), 1453; https://doi.org/10.3390/diagnostics13081453 - 18 Apr 2023
Cited by 1 | Viewed by 1106
Abstract
Multikinase inhibitors (MKIs) such as sorafenib and lenvatinib are first-line treatments for unresectable hepatocellular carcinoma (HCC) and are known to have immunomodulatory effects. However, predictive biomarkers of MKI treatment in HCC patients need to be elucidated. In the present study, thirty consecutive HCC [...] Read more.
Multikinase inhibitors (MKIs) such as sorafenib and lenvatinib are first-line treatments for unresectable hepatocellular carcinoma (HCC) and are known to have immunomodulatory effects. However, predictive biomarkers of MKI treatment in HCC patients need to be elucidated. In the present study, thirty consecutive HCC patients receiving lenvatinib (n = 22) and sorafenib (n = 8) who underwent core-needle biopsy before treatment were enrolled. The associations of CD3, CD68, and programmed cell death-ligand-1 (PD-L1) immunohistochemistry with patient outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), were evaluated. High and low subgroups were determined according to median CD3, CD68, and PD-L1 values. Median CD3 and CD68 counts were 51.0 and 46.0 per 20,000 µm2, respectively. The median combined positivity score (CPS) of PD-L1 was 2.0. Median OS and PFS were 17.6 and 4.4 months, respectively. ORRs of the total, lenvatinib, and sorafenib groups were 33.3% (10/30), 12.5% (1/8), and 40.9% (9/22), respectively. The high CD68+ group had significantly better PFS than the low CD68+ group. The high PD-L1 group had better PFS than the low subgroup. When we analyzed the lenvatinib subgroup, PFS was also significantly better in the high CD68+ and PD-L1 groups. These findings suggest that high numbers of PD-L1-expressing cells within tumor tissue prior to MKI treatment can serve as a biomarker to predict favorable PFS in HCC patients. Full article
(This article belongs to the Special Issue Clinicopathology and Prognosis of Hepatocellular Carcinoma)
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15 pages, 5916 KiB  
Article
U1RNP/lncRNA/Transcription Cycle Axis Promotes Tumorigenesis of Hepatocellular Carcinoma
by Shun Li, Shuaiyin Zhang, Mingle Huang, Huanjing Hu and Yubin Xie
Diagnostics 2022, 12(5), 1133; https://doi.org/10.3390/diagnostics12051133 - 03 May 2022
Cited by 2 | Viewed by 1941
Abstract
As a component of the spliceosome, U1 small nuclear ribonucleoproteins (U1RNPs) play critical roles in RNA splicing, and recent studies have shown that U1RNPs could recruit long non-coding RNAs (lncRNAs) to chromatin which are involved in cancer development. However, the interplay of U1 [...] Read more.
As a component of the spliceosome, U1 small nuclear ribonucleoproteins (U1RNPs) play critical roles in RNA splicing, and recent studies have shown that U1RNPs could recruit long non-coding RNAs (lncRNAs) to chromatin which are involved in cancer development. However, the interplay of U1 snRNP, lncRNAs and downstream genes and signaling pathways are insufficiently understood in hepatocellular carcinoma (HCC). The expression of U1RNPs was found to be significantly higher in tumors than normal tissues in liver hepatocellular carcinomas of The Cancer Genome Atlas (TCGA-LIHC) dataset. LncRNAs with potential U1-binding sites (termed U1-lncRNAs) were found to be mostly located in the nucleus and their expression was higher in tumor than in normal tissues Bioinformatic analysis indicated that U1-lncRNAs worked with RNA-binding proteins and regulated the transcription cycle in HCC. A U1-lncRNA risk model was constructed using a TCGA dataset, and the AUCs of this risk model to predict 1-, 3- and 5-year overall survival were 0.82, 0.84 and 0.8, respectively. Furthermore, silencing of the small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) resulted in impaired proliferation, G1/M cell cycle arrest and downregulation of transcription-cycle-related genes in HCC cell lines. Taken together, these results indicate that U1RNPs interact with lncRNAs and promote the transcription cycle process in HCC, which suggests that these could be novel biomarkers in the clinical management of HCC. Full article
(This article belongs to the Special Issue Clinicopathology and Prognosis of Hepatocellular Carcinoma)
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15 pages, 54447 KiB  
Article
Tubulin Alpha 1b Is Associated with the Immune Cell Infiltration and the Response of HCC Patients to Immunotherapy
by Xinyao Hu, Hua Zhu, Biao Chen, Xiaoqin He, Yang Shen, Xiaoyu Zhang, Wenliang Chen, Xin Liu, Yangtao Xu and Ximing Xu
Diagnostics 2022, 12(4), 858; https://doi.org/10.3390/diagnostics12040858 - 30 Mar 2022
Cited by 13 | Viewed by 2694
Abstract
Tubulin alpha 1b (TUBA1B) is an important microtubule isoform that is involved in the formation of the cytoskeleton. The objective of our study was to explore the potential of TUBA1B in predicting the prognosis of HCC and patients’ response to immunotherapy. Raw data [...] Read more.
Tubulin alpha 1b (TUBA1B) is an important microtubule isoform that is involved in the formation of the cytoskeleton. The objective of our study was to explore the potential of TUBA1B in predicting the prognosis of HCC and patients’ response to immunotherapy. Raw data was extracted from TCGA and GEO databases, and then HCCDB, TIMER, HPA, and GEPIA websites, as well as R software, were used to perform bioinformatics analysis to investigate the potential of TUBA1B as a prognostic and immunotherapeutic marker for hepatocellular carcinoma (HCC). We found that both TUBA1B mRNA and protein were highly expressed in HCC. TUBA1B was proved to be an independent prognostic predictor of HCC. Additionally, TUBA1B expression was associated with the infiltration of several immune cells in HCC. Moreover, TUBA1B was coexpressed with immune-related genes and immune checkpoints. Patients expressing high TUBA1B responded better to immune checkpoint inhibitor (ICI) therapy. GO and KEGG analyses revealed that TUBA1B may be involved in the processes of cell cycle, spliceosome, and DNA replication. In conclusion, TUBA1B is expected to be a prognostic and immunotherapeutic marker for HCC. Full article
(This article belongs to the Special Issue Clinicopathology and Prognosis of Hepatocellular Carcinoma)
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14 pages, 1497 KiB  
Article
Dynamic Change of Albumin-Bilirubin Score Is Good Predictive Parameter for Prognosis in Chronic Hepatitis C-hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization
by Po-Ting Lin, Wei Teng, Wen-Juei Jeng, Wei-Ting Chen, Yi-Chung Hsieh, Chien-Hao Huang, Kar-Wai Lui, Chen-Fu Hung, Ching-Ting Wang, Pei-Mei Chai, Chen-Chun Lin, Chun-Yen Lin, Shi-Ming Lin and I-Shyan Sheen
Diagnostics 2022, 12(3), 665; https://doi.org/10.3390/diagnostics12030665 - 09 Mar 2022
Cited by 4 | Viewed by 2126
Abstract
Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is [...] Read more.
Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is seldom discussed. Therefore, this study aimed to investigate the application of ALBI grade and dynamic change of ALBI grade (delta ALBI grade) after first TACE for prognosis prediction in HCC patients with chronic hepatitis C infection. Method: From January 2005 to December 2015, newly diagnosed naive chronic hepatitis C-hepatocellular carcinoma (CHC-HCC) patients who were treated with TACE as the initial treatment at the Chang Gung Memorial Hospital, Linkou Medical Center, were retrospectively recruited. The pre-treatment host factors, tumor status and noninvasive markers were collected. The Cox regression model was used to identify independent predictors of overall survival and tumor recurrence. Results: Among 613 treatment-naive CHC-HCC patients, 430 patients died after repeated TACE during a median follow-up of 26.9 months. Complete remission after repeated TACE occurred in 46.2% patients, and 208 patients (33.9%) had tumor recurrence, with a median recurrence-free interval of 8.5 months. In Cox regression analysis, ALBI grade II/III (aHR: 1.088, p = 0.035) and increased delta ALBI grade (aHR: 1.456, p = 0.029) were independent predictive factors for tumor recurrence. Furthermore, ALBI grade II/III (aHR: 1.451, p = 0.005) and increased delta ALBI grade during treatment (aHR: 1.436, p = 0.006) were predictive factors for mortality, while achieving complete response after repeated TACE (aHR: 0.373, p < 0.001) and anti-viral therapy (aHR: 0.580, p = 0.002) were protective factors for mortality. Conclusion: Both ALBI and delta ALBI grade are independent parameters to predict survival and tumor recurrence of CHC-HCC patients receiving TACE treatment. Full article
(This article belongs to the Special Issue Clinicopathology and Prognosis of Hepatocellular Carcinoma)
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