Review
Biochemistry & Molecular Biology
Zeno Sparchez, Rares Craciun, Iuliana Nenu, Lavinia Patricia Mocan, Mihaela Sparchez, Tudor Mocan
Summary: In recent years, the field of hepatocellular carcinoma has seen significant changes, emphasizing different HCC phenotypes and the emergence of novel, specific therapies that pave the way for personalized treatment of primary liver cancer. The role of liver biopsy has slowly shifted from a confirmatory method to a technique capable of providing in-depth characterization of nodules. It is expected that liver biopsy will regain its position in HCC, and combining it with other available methods could improve treatment selection and outcomes.
Review
Biochemistry & Molecular Biology
Agnieszka Kopystecka, Rafal Patryn, Magdalena Lesniewska, Julia Budzynska, Ilona Koziol
Summary: Hepatocellular carcinoma (HCC) is a common primary liver cancer with a poor prognosis. Imaging and liver biopsy have limitations in detecting small nodules and atypical features. Liquid biopsy and molecular analysis provide new biomarkers for early diagnosis and monitoring of HCC. ctDNA testing can benefit patients with liver and biliary malignancies, indicating personalized cancer treatment based on specific tumor DNA mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Tao Yan, Lingxiang Yu, Ning Zhang, Caiyun Peng, Guodong Su, Yi Jing, Linzhi Zhang, Tong Wu, Jiamin Cheng, Qian Guo, Xiaoliang Shi, Yinying Lu
Summary: Recent advancements in precision medicine, clinical diagnoses, treatments, and innovative research have led to important breakthroughs in the care of hepatocellular carcinoma (HCC). This includes the discovery of new biomarkers, the promotion of liquid biopsy technologies, and advancements in targeted therapy and immunotherapy. Multiomics technologies have provided a deeper understanding of the characteristics of HCC. The promotion of accurate typing, treatment guidance, and prognosis has provided more treatment opportunities and extended survival timelines for HCC patients.
CANCER BIOLOGY & MEDICINE
(2022)
Review
Engineering, Multidisciplinary
Ghassan K. Abou-Alfa, Lin Wu, Augusto Villanueva
Summary: Early detection of hepatocellular carcinoma is crucial for reducing mortality rates, but sensitive biomarkers are still lacking. Research into circulating tumor-derived molecular features, such as circulating tumor DNA and RNA, has potential for noninvasive biomarker candidates in various tumor types.
Article
Oncology
Sheehyun Kim, Yoojoo Lim, Jun-Kyu Kang, Hwang-Phill Kim, Hanseong Roh, Su Yeon Kim, Dongin Lee, Duhee Bang, Seung-Yong Jeong, Kyu Joo Park, Sae-Won Han, Tae-You Kim
Summary: This study analyzed serial blood samples from metastatic colorectal cancer patients and sequenced ctDNA to evaluate its clinical utility. The results showed that ctDNA clearance after chemotherapy was associated with longer progression-free survival, independent of radiological response. Longitudinal ctDNA monitoring detected ctDNA progression earlier than radiological progressive disease in a significant percentage of patients.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Joseph W. Franses, Mir Lim, Adam M. Burgoyne, Kabir Mody, Jochen Lennerz, Jeremy Chang, Robin Imperial, Stacey N. Dybel, Thi M. Dinh, Jude Masannat, Caroline M. Weipert, David Hsiehchen
Summary: This study provides the first landscape of blood tumor mutational burden (bTMB) in advanced hepatocellular carcinoma (HCC) using a commercially available next-generation sequencing assay. The results show that bTMB is approximately three times higher than matched tissue TMB, and it correlates with NAFLD cirrhosis etiology and the presence of genomic alterations in HTERT and TP53.
Editorial Material
Biochemistry & Molecular Biology
Alessandro Passardi, Emanuela Scarpi, Paola Ulivi
Summary: This editorial summarizes six scientific papers on molecular and translational research on colorectal cancer, contributing to the current understanding of potential biomarkers and treatment targets. It aims to identify new strategies to improve diagnostic and therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Johann von Felden, Amanda J. Craig, Teresa Garcia-Lezana, Ismail Labgaa, Philipp K. Haber, Delia D'Avola, Amon Asgharpour, Douglas Dieterich, Antoinette Bonaccorso, Miguel Torres-Martin, Daniela Sia, Max W. Sung, Parissa Tabrizian, Myron Schwartz, Josep M. Llovet, Augusto Villanueva
Summary: This study reveals the mutational landscape of advanced HCC and identifies predictive biomarkers for response to systemic therapies. Mutations in the PI3K/MTOR pathway are associated with shorter PFS after tyrosine kinase inhibitor treatment, while WNT pathway mutations are not predictive of response after CPI therapy.
Review
Oncology
Shufang Zheng, Hanrui Bian, Jintong Li, Yumeng Shen, Yong Yang, Weiwei Hu
Summary: Differentiation therapy for hepatocellular carcinoma aims to restore normal liver characteristics of tumor cells, suppress malignant phenotype, and induce differentiation into hepatocyte-like cells. Understanding the molecular and signaling pathways controlling HCC differentiation is crucial for inducing differentiation therapy.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Oncology
Siyu Fu, Jose D. Debes, Andre Boonstra
Summary: Hepatocellular carcinoma (HCC) is a common primary liver malignancy with poor prognosis. Epigenetic modification, specifically DNA methylation, plays a significant role in HCC development by impacting cell differentiation, proliferation, and function. Methylated DNA markers have shown promise as specific biomarkers for early-stage HCC detection, offering higher sensitivity and specificity compared to current surveillance methods. However, the immediate application of these biomarkers is limited by various factors. This review provides a detailed rationale for using methylation biomarkers in HCC detection and summarizes recent studies on methylated DNA markers, emphasizing the importance of the underlying cause of liver disease in cancer mechanisms.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Hye Won Lee, Esl Kim, Kyung Joo Cho, Hye Jung Park, Jieun Seo, Hyeonah Lee, Eunha Baek, Jong Rak Choi, Kwang-Hyub Han, Seung-Tae Lee, Jun Yong Park
Summary: Molecular barcode sequencing in liquid biopsy has the potential to detect hepatocellular carcinoma and provide personalized information about tumor biology, guiding clinical diagnosis, management, and prognostic stratification.
LIVER INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Tania Rossi, Giulia Gallerani, Giovanni Martinelli, Roberta Maltoni, Francesco Fabbri
Summary: Breast cancer is characterized by high heterogeneity, with circulating tumor cells playing a crucial role in metastasis. While CTCs have shown promise as a liquid biopsy for studying cancer progression and guiding treatment, they are not currently used in clinical practice for personalized medicine.
Review
Medicine, General & Internal
Zhenxiao Wang, Hanjiao Qin, Shui Liu, Jiyao Sheng, Xuewen Zhang
Summary: Hepatocellular carcinoma (HCC) is the most common primary hepatocellular carcinoma (PHC), and early diagnosis is crucial for better prognosis. Recent advancements in precision medicine and understanding the biological mechanisms of HCC have led to the development of new diagnostic methods, such as emerging serum markers, liquid biopsies, molecular diagnosis, and improvements in imaging techniques. This review aims to summarize and analyze these scientific advances in early HCC diagnosis and discuss their application and limitations, providing a reference for further research and clinical practice.
CHINESE MEDICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Caecilia Sukowati, Loraine Kay D. Cabral, Beatrice Anfuso, Francesco Dituri, Roberto Negro, Gianluigi Giannelli, Claudio Tiribelli
Summary: This study investigates the potential of a combination strategy using immunotherapy and epigenetic reprogramming against hepatocellular carcinoma (HCC). The results show that combination therapy of PD-L1 silencing and 5-AZA treatment can effectively inhibit the growth of HCC cells, indicating its potential use as a treatment for heterogeneous HCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Huang Ao, Zhang Xin, Zhou Jian
Summary: Immunotherapy, particularly immune checkpoint inhibitors, has made significant progress in the management of hepatocellular carcinoma (HCC), but the challenge of identifying the optimal responders to ICIs treatment and monitoring treatment effects in a timely manner remains. Liquid biopsy may offer a promising approach to address tumor heterogeneity, identify patients who respond to immunotherapy, monitor treatment effects, and uncover resistance mechanisms.
BIOMARKER RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Cerise Yuen-Ki Chan, Vincent Wai-Hin Yuen, David Kung-Chun Chiu, Chi-Ching Goh, Kelsie L. Thu, David W. Cescon, Isabel Soria-Bretones, Cheuk-Ting Law, Jacinth Wing-Sum Cheu, Derek Lee, Aki Pui-Wah Tse, Kel Vin Tan, Misty Shuo Zhang, Bowie Po-Yee Wong, Chun-Ming Wong, Pek-Lan Khong, Irene Oi-Lin Ng, Mark R. Bray, Tak Wah Mak, Thomas Chung-Cheung Yau, Carmen Chak-Lui Wong
Summary: This study found that targeting the centrosome regulator PLK4 to activate the cytosolic DNA sensing-mediated immune response effectively suppressed tumor progression in late-stage mouse HCC through cell cycle inhibition and induction of antitumor immunity, presenting a durable suppressive effect.
Article
Gastroenterology & Hepatology
Xia Wang, Hongyang Huang, Karen Man-Fong Sze, Jin Wang, Lu Tian, Jingyi Lu, Yu-Man Tsui, Hoi Tang Ma, Eva Lee, Ao Chen, Joyce Lee, Ying Wang, Judy Wai Ping Yam, Tan-To Cheung, Xinyuan Guan, Irene Oi-Lin Ng
Summary: The study found that S100A10 plays an important role in the progression of HCC by transferring in extracellular vesicles (EV-S100A10) and regulating the protein cargoes of EVs. EV-S100A10 may be a potential therapeutic target and biomarker for HCC progression.
Article
Gastroenterology & Hepatology
Yung-Tuen Chiu, Abdullah Husain, Karen Man-Fong Sze, Daniel Wai-Hung Ho, Eliana Mary Senires Suarez, Xia Wang, Eva Lee, Hoi-Tang Ma, Joyce Man-Fong Lee, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: This study identified Mid-line 1 interacting protein 1 (MID1IP1) as a key gene in the metastasis of hepatocellular carcinoma (HCC). It was found that MID1IP1 promoted HCC migration and invasion by upregulating FOS like 1 (FRA1) and subsequently activating MMP9 signaling. Targeting the MID1IP1-mediated FRA1 pathway may be a potential therapeutic strategy against HCC progression.
Review
Cell Biology
Tina Suoangbaji, Vanilla Xin Zhang, Irene Oi-Lin Ng, Daniel Wai-Hung Ho
Summary: Primary liver cancer (PLC), including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is a major cause of cancer-related deaths worldwide. Surgical resection and liver transplantation are curative therapies for PLC, but many cases are inoperable and have a high rate of recurrence. Mouse models and single-cell RNA sequencing have played crucial roles in understanding PLC and identifying potential targets for treatment. This review summarizes recent studies that used these approaches, focusing on cellular and molecular components, and discusses the potential insights they can provide.
Article
Gastroenterology & Hepatology
Yi Xu, Yue Yao, Liang Yu, Hiu Ling Fung, Alexander Hin Ning Tang, Irene Oi-Lin Ng, Melody Y. M. Wong, Chi-Ming Che, Jing Ping Yun, Yunfu Cui, Judy Wai Ping Yam
Summary: This study reveals the role of CLTA in the uptake of sEVs to promote HCC progression. CLTA is overexpressed in tumor tissues compared to non-tumorous liver tissues and increases progressively with tumor stage. CLTA contributes to sEV uptake in cells, leading to enhanced cancerous properties of HCC. Mechanistically, CLTA increases CAPG expression to facilitate sEV uptake, thereby promoting proliferation, motility, and invasiveness of HCC cells. Additionally, the CLTA inhibitor Pitstop 2 alone or in combination with sorafenib attenuated tumor growth in mice implanted with PDXs.
HEPATOLOGY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Jacinth Wing-Sum Cheu, David Kung-Chun Chiu, Kenneth Kin-Leung Kwan, Chunxue Yang, Vincent Wai-Hin Yuen, Chi Ching Goh, Noreen Nog-Qin Chui, Wei Shen, Cheuk-Ting Law, Qidong Li, Misty Shuo Zhang, Macus Hao-Ran Bao, Bowie Po -Yee Wong, Cerise Yuen-Ki Chan, Cindy Xinqi Liu, Grace Fu -Wan Sit, Zher Yee Ooi, Haijing Deng, Aki Pui-Wah Tse, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Summary: Hypoxia-induced adenosine creates an immunosuppressive tumor microenvironment (TME) and dampens the efficacy of immune checkpoint inhibitors (ICIs). HIF-1 orchestrates adenosine efflux through activation of MXI1 and equilibrative nucleoside transporter 4, leading to adenosine accumulation in cancer cells and elevated extracellular adenosine levels. The immunosuppressive role of adenosine on immune cells was confirmed in vitro assays, and therapeutic combination of adenosine receptor antagonists and anti-PD-1 prolonged survival of HCC-bearing mice. This study highlights the importance of targeting adenosine in overcoming immune resistance in HCC.
Article
Medicine, General & Internal
Philip C. Haycock, Maria Carolina Borges, Kimberley Burrows, Rozenn N. Lemaitre, Stephen Burgess, Nikhil K. Khankari, Konstantinos K. Tsilidis, Tom R. Gaunt, Gibran Hemani, Jie Zheng, Therese Truong, Brenda M. Birmann, Tracy OMara, Amanda B. Spurdle, Mark M. Iles, Matthew H. Law, Susan L. Slager, Fatemeh Saberi Hosnijeh, Daniela Mariosa, Michelle Cotterchio, James R. Cerhan, Ulrike Peters, Stefan Enroth, Puya Gharahkhani, Loic Le Marchand, Ann C. Williams, Robert C. Block, Christopher I. Amos, Rayjean J. Hung, Wei Zheng, Marc J. Gunter, George Davey Smith, Caroline Relton, Richard M. Martin
Summary: Using Mendelian randomization, this study found that polyunsaturated fatty acids (PUFAs) may be causally related to colorectal cancer and esophageal squamous cell carcinoma, but they also increase the risk of inflammatory bowel disease.
Article
Pathology
Kristy Kwan-Shuen Chan, Kwan-Yung Au, Long-Hin Suen, Bernice Leung, Cheuk-Yan Wong, Wei-Qiang Leow, Tony Kiat-Hon Lim, Irene Oi-Lin Ng, Clive Yik-Sham Chung, Regina Cheuk-Lam Loz
Summary: The study reveals the functional role of sortilin in hepatocarcinogenesis by modulating the cancer secretome and deregulated lipid metabolism.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Hongyang Huang, Yu-Man Tsui, Daniel Wai-Hung Ho, Clive Yik-Sham Chung, Karen Man-Fong Sze, Eva Lee, Gary Cheuk-Hang Cheung, Vanilla Xin Zhang, Xia Wang, Xueying Lyu, Irene Oi-Lin Ng
Summary: This study identified LANCL1 as a key cell surface protein that promotes HCC tumor initiation. LANCL1 stabilizes FAM49B to suppress ROS production and promote HCC tumorigenicity. Clinically, high co-expression of LANCL1 and FAM49B is associated with more advanced tumor stage and poorer prognosis in HCC.
Article
Chemistry, Multidisciplinary
Samuel Wan Ki Wong, Sze Keong Tey, Xiaowen Mao, Hiu Ling Fung, Zhi-Jie Xiao, Danny Ka Ho Wong, Lung-Yi Mak, Man-Fung Yuen, Irene Oi-Lin Ng, Jing Ping Yun, Yi Gao, Judy Wai Ping Yam
Summary: Hepatocellular carcinoma (HCC) growth and dissemination are driven by tumor-derived small extracellular vesicles (sEVs) and the upregulation of von Willibrand factor (vWF) along HCC stages. Elevated sEV-vWF levels promote angiogenesis, tumor-endothelial adhesion, pulmonary vascular leakiness, and metastasis in late-stage HCC patients. sEV-vWF modulates endothelial cells through increased VEGF-A and FGF2 levels, with FGF2 stimulating a positive feedback response in HCC via the FGFR4/ERK1 signaling pathway. Blocking tumor-endothelial intercellular communication through anti-vWF antibody or FGFR inhibitor improves the treatment outcome of sorafenib in a patient-derived xenograft mouse model, suggesting a new therapeutic strategy.
Article
Gastroenterology & Hepatology
Charles Shing Kam, Daniel Wai-Hung Ho, Vanessa Sheung-In Ming, Lu Tian, Karen Man-Fong Sze, Vanilla Xin Zhang, Yu-Man Tsui, Abdullah Husain, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Albert Chi-Yan Chan, Tan-To Cheung, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: The up-regulation of PFKFB4 expression is associated with more aggressive tumor behavior in hepatocellular carcinoma (HCC) and plays a critical role in HCC development, with therapeutic implications.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Martina Mang Leng Lei, Carmen Oi Ning Leung, Eunice Yuen Ting Lau, Rainbow Wing Hei Leung, Victor Wan San Ma, Man Tong, Yin Ying Lu, Chen Yang Huang, Qiao Hua Zhu, Irene Oi Lin Ng, Stephanie Ma, Terence Kin Wah Lee
Summary: This study reveals that SCYL3 plays a critical role in promoting the progression of hepatocellular carcinoma (HCC). It is often overexpressed in HCC, especially in metastatic tumors, and is associated with worse patient survival. Suppression of SCYL3 attenuates cell proliferation, migration, and in vivo metastasis in HCC.
Article
Gastroenterology & Hepatology
Jacinth Wing-Sum Cheu, Derek Lee, Qidong Li, Chi Ching Goh, Macus Hao-Ran Bao, Vincent Wai-Hin Yuen, Misty Shuo Zhang, Chunxue Yang, Cerise Yuen-Ki Chan, Aki Pui-Wah Tse, Grace Fu-Wan Sit, Cindy Xinqi Liu, Irene Oi-Lin Ng, Chun-Ming Wong, Carmen Chak-Lui Wong
Summary: This study identified FSP1 as a potential therapeutic target for hepatocellular carcinoma (HCC). Inhibiting FSP1 induced ferroptosis, enhanced the anti-tumor immune response, and effectively suppressed HCC tumor growth. FSP1 inhibition represents a new therapeutic strategy for HCC.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)