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Cancers
Special Issues
Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer
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Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 3243

Special Issue Editors

Dr. Wai-Hung Ho Daniel

E-Mail Website
Guest Editor
Department of Pathology and State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
Interests: liver cancer; cancer genomics; bioinformatics; HBV; single-cell and spatial transcriptomics; computational biology
Special Issues, Collections and Topics in MDPI journals
Dr. Yuman Tsui

E-Mail Website
Guest Editor
1. Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong
2. State Key Laboratory of Liver Research, The University of Hong Kong, Pokfulam, Hong Kong
Interests: hepatocellular carcinoma (HCC); tumor initiating cells (TICs); translational aspects for liver cancer treatment; liquid biopsy

Special Issue Information

Dear Colleagues,

Liver cancer is a leading fatal human cancer. It is known to have a high degree of heterogeneity, leading to frequent treatment resistance and disease recurrence. There are a limited number of treatment options and they are not adequately effective. The hepatocarcinogenesis process of liver cancer is complex and involves the endeavor of malignant and immune components. There is an accumulation of various genetic and epigenetic alterations that pinpoint key signaling pathways or biological processes. With the emergence of different sequencing-based strategies, high-throughput screening platforms as well as computational algorithms, we can delineate the underlying molecular and cellular landscapes in liver cancer to a better extent. This Special Collection will focus on various niche areas that cover the basic as well as translational aspects of liver cancer research.

This Special Issue will include the following topics:

- Tumor heterogeneity;

- Transcriptomic landscape;

- Genomic landscape;

- Epigenetic landscape;

- Cellular landscape;

- Single-cell analysis;

- Spatial transcriptomics;

- Tumor microenvironment;

- Liver cancer stem cell;

- Liquid biopsy;

- Biomarkers.

Dr. Wai-Hung Ho Daniel
Dr. Yuman Tsui
Guest Editors

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 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. Cancers 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 2900 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

  • liver cancer
  • NGS
  • single-cell sequencing
  • cancer genomics
  • cellular and molecular landscapes
  • tumor microenvironment
  • tumor heterogeneity
  • liver cancer stem cell
  • liquid biopsy
  • biomarkers

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Published Papers (3 papers)

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Research

11 pages, 9159 KiB  
Article
LiverSCA 2.0: An Enhanced Comprehensive Cell Atlas for Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
by Tina Suoangbaji, Renwen Long, Irene Oi-Lin Ng, Loey Lung-Yi Mak and Daniel Wai-Hung Ho
Cancers 2025, 17(5), 890; https://doi.org/10.3390/cancers17050890 - 5 Mar 2025
Viewed by 700
Abstract
Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct types of primary liver cancer (PLC) characterized by considerable extents of cellular and molecular heterogeneities. We recently developed a web-based cell atlas called LiverSCA that possesses a user-friendly interface and comprehensive functionalities. [...] Read more.
Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct types of primary liver cancer (PLC) characterized by considerable extents of cellular and molecular heterogeneities. We recently developed a web-based cell atlas called LiverSCA that possesses a user-friendly interface and comprehensive functionalities. It facilitates the exploration of gene expression patterns, cellular compositions, and intercellular communication within the microenvironments of liver and PLC tumors. Methods: To further enhance the documentation of data pinpointing different phenotypes/subtypes of liver and PLC, we extended the catalog of LiverSCA with additional datasets, e.g., ICC and metabolic dysfunction-associated steatotic liver disease/steatosis (MASLD/MASH). Results: The current enhanced version of the LiverSCA cell atlas encompasses six phenotypes (normal, HBV-HCC, HCV-HCC, non-viral HCC, ICC, and MASH), 63 patients, and over 248,000 cells. Furthermore, we have incorporated comparative visualization methods that allow users to simultaneously examine and compare gene expression levels between two different phenotypes. Conclusions: We are committed to the continuous development of LiverSCA and envision that it will serve as a valuable resource to support researchers in convenient investigations into the cellular and molecular landscapes of liver and PLC. Full article
(This article belongs to the Special Issue Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer)
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16 pages, 4371 KiB  
Article
DNA Methylation Panels for the Differentiation of Lung and Gastric Adenocarcinomas from Other Common Primary Adenocarcinomas
by Tina Draškovič, Lara Omahen, Maja Jerše, Nina Zidar and Nina Hauptman
Cancers 2024, 16(23), 4000; https://doi.org/10.3390/cancers16234000 - 29 Nov 2024
Viewed by 863
Abstract
Background/Objectives: Gastric and lung adenocarcinomas are among the most common adenocarcinomas worldwide. Our research aimed to validate methylation biomarkers that differentiate gastric and lung adenocarcinomas from hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma and paired healthy tissues. Methods: The study analyzed [...] Read more.
Background/Objectives: Gastric and lung adenocarcinomas are among the most common adenocarcinomas worldwide. Our research aimed to validate methylation biomarkers that differentiate gastric and lung adenocarcinomas from hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma and paired healthy tissues. Methods: The study analyzed 178 formalin-fixed, paraffin-embedded tissue samples, including 14 gastric adenocarcinomas, 15 lung adenocarcinomas, 15 hepatocellular carcinomas, 15 cholangiocarcinomas, 15 colorectal carcinomas, 15 pancreatic adenocarcinomas and their paired healthy tissues. Methylation status was determined experimentally by methylation-sensitive high resolution melting. The diagnostic panels were validated on bioinformatics datasets from The Cancer Genome Atlas and Gene Expression Omnibus, comprising 1981 and 773 samples, respectively. Sensitivity, specificity, diagnostic accuracy and predictive values for each cancer type were calculated for the experimental, Gene Expression Omnibus and The Cancer Genome Atlas datasets. Results: The gastric cancer-specific panel showed a sensitivity of 78.6–83.9%, a specificity of 86.6–94.6% and a diagnostic accuracy of 89.9–96.1% to differentiate between all tumors, and a sensitivity of 78.6–83.9%, a specificity of 89.2–96.4% and a diagnostic accuracy of 88–96.1% to differentiate between all tumors and healthy tissues. The lung adenocarcinoma-specific panel showed a sensitivity of 61.1–93.3%, a specificity of 70.3–90.8% and a diagnostic accuracy of 74.2–90.6% to differentiate between all tumors, and a sensitivity of 61.1–93.3%, a specificity of 77.9–93.4% and a diagnostic accuracy of 79.2% to 93.1% to differentiate between all tumors and healthy tissues. Conclusions: This study demonstrates the potential of using diagnostic methylation panels to differentiate gastric and lung adenocarcinomas from other common adenocarcinomas and paired healthy tissues. Full article
(This article belongs to the Special Issue Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer)
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12 pages, 2093 KiB  
Article
Resolution of Optimal Mitochondrial and Nuclear DNA Enrichment in Target-Panel Sequencing and Physiological Mitochondrial DNA Copy Number Estimation in Liver Cancer and Non-Liver Cancer Subjects
by Xue-Ying Lyu, Yu-Man Tsui, Ivan Ka-Kit Tam, Po-Man Li, Gary Cheuk-Hang Cheung, Joyce Man-Fong Lee, Irene Oi-Lin Ng and Daniel Wai-Hung Ho
Cancers 2024, 16(17), 3012; https://doi.org/10.3390/cancers16173012 - 29 Aug 2024
Cited by 1 | Viewed by 1087
Abstract
Mitochondria generate energy to support cells. They are important organelles that engage in key biological pathways. The dysfunction of mitochondria can be linked to hepatocarcinogenesis, which has been actively explored in recent years. To investigate the mitochondrial dysfunction caused by genetic variations, target-panel [...] Read more.
Mitochondria generate energy to support cells. They are important organelles that engage in key biological pathways. The dysfunction of mitochondria can be linked to hepatocarcinogenesis, which has been actively explored in recent years. To investigate the mitochondrial dysfunction caused by genetic variations, target-panel sequencing is a flexible and promising strategy. However, the copy number of mitochondria generally exceeds nuclear DNA, which raises a concern that uneven target enrichment of mitochondrial DNA (mtDNA) and nuclear DNA (ncDNA) in target-panel sequencing would lead to an undesirably biased representation of them. To resolve this issue, we evaluated the optimal pooling of mtDNA probes and ncDNA probes by a series of dilutions of mtDNA probes in both genomic DNA (gDNA) and cell-free DNA (cfDNA) samples. The evaluation was based on read count, average sequencing depth and coverage of targeted regions. We determined that an mtDNA:ncDNA probe ratio of around 1:10 would offer a good balance of sequencing performance and cost effectiveness. Moreover, we estimated the median physiological mtDNA:ncDNA copy ratio as 38.1 and 2.9 in cfDNA and gDNA samples of non-liver cancer subjects, respectively, whereas they were 20.0 and 2.1 in the liver cancer patients. Taken together, this study revealed the appropriate pooling strategy of mtDNA probes and ncDNA probes in target-panel sequencing and suggested the normal range of physiological variation of the mtDNA:ncDNA copy ratio in non-liver cancer individuals. This can serve as a useful reference for future target-panel sequencing investigations of the mitochondrial genome in liver cancer. Full article
(This article belongs to the Special Issue Molecular Genetics, Signaling Pathways, and Therapeutic Strategies for Liver Cancer)
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