scholarly journals Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy

2017 ◽  
Vol 18 (2) ◽  
pp. 405 ◽  
Author(s):  
Maryam Tahmasebi Birgani ◽  
Vinicio Carloni
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment

Status and Development of The Tumor Microenvironment in Hepatocellular Carcinoma*

2012 ◽  
Vol 39 (5) ◽  
pp. 416-422
Author(s):  
Zhi-Lei LIU ◽  
Wei SUN ◽  
Fu-Chu HE ◽  
Xian-Ling CONG ◽  
Ying JIANG
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment

scholarly journals Is the Rationale of Anatomical Liver Resection for Hepatocellular Carcinoma Universally Adoptable? A Hypothesis-Driven Review

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 131
Author(s):  
Young-Jen Lin ◽  
Cheng-Maw Ho
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Surgical Resection ◽  
Tumor Recurrence ◽  
Hepatic Metastases ◽  
Vascular Supply ◽  
Tumor Ablation ◽  
Supporting Evidence ◽  
En Bloc ◽  
Margin Width

Surgical resection is the first-line curative treatment modality for resectable hepatocellular carcinoma (HCC). Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR. In this article, we propose the rationale for AR and its universal adoption by providing supporting evidence from the advanced understanding of a tumor microenvironment and accumulating clinical experiences of locoregional tumor ablation therapeutics. AR may be advantageous because it completely removes the en-bloc by interrupting tumor vascular supply and thus extirpates the spreading of tumor microthrombi, if they ever exist, within the supplying portal vein. However, HCC is a hypervascular tumor that can promote neoangiogenesis in the local tumor microenvironment, which in itself can break through the anatomical boundary within the liver and even retrieve nourishment from extrahepatic vessels, such as inferior phrenic or omental arteries. Additionally, increasing clinical evidence for locoregional tumor ablation therapies, such as radiofrequency ablation, predominantly performed as a non-anatomical approach, suggests comparable outcomes for surgical resection, particularly in small HCC and colorectal, hepatic metastases. Moreover, liver transplantation for HCC, which can be considered as AR of the whole liver followed by implantation of a new graft, is not universally free from post-transplant tumor recurrence. Overall, AR should not be considered the gold standard among all surgical resection methods. Surgical resection is fundamentally reliant on choosing the optimal margin width to achieve en-bloc tumor niche removal while balancing between oncological radicality and the preservation of postoperative liver function. The importance of this is to liberate surgical resilience in hepatocellular carcinoma. The overall success of HCC treatment is determined by the clearance of the theoretical niche. Developing biomolecular-guided navigation device/technologies may provide surgical guidance toward the total removal of microscopic tumor niche to achieve superior oncological outcomes.

scholarly journals New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Crucial Role ◽  
Human Cancer ◽  
Metabolic Adaptation ◽  
Advanced Hcc ◽  
Diagnosis And Prognosis ◽  
Competitive Endogenous Rnas ◽  
Growing Body

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

scholarly journals Multiparametric Analyses of Hepatocellular Carcinoma Somatic Mouse Models and Their Associated Tumor Microenvironment

2021 ◽  
Vol 1 (6) ◽  
Author(s):  
Daniel Taranto ◽  
Christel F.A. Ramirez ◽  
Serena Vegna ◽  
Marnix H.P. Groot ◽  
Niels Wit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Mouse Models

scholarly journals Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110162
Author(s):  
Yangming Hou ◽  
Xin Wang ◽  
Junwei Wang ◽  
Xuemei Sun ◽  
Xinbo Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Proportional Hazards ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Cyclin B1 ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Tumor Promoter ◽  
Protein Protein Interaction

Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

scholarly journals A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu-Tzu Liu ◽  
Tai-Chung Tseng ◽  
Ruey-Shyang Soong ◽  
Chun-Yi Peng ◽  
Yu-Hsing Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Mouse Model ◽  
T Cell Exhaustion ◽  
Cell Exhaustion

scholarly journals M6a Regulator-Associated Methylation Modification Patterns Shape Tumor Microenvironment Characteristics in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Bobin Ning ◽  
Yonggan Xue ◽  
Hongyi Liu ◽  
Hongyu Sun ◽  
Baoqing Jia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Signaling Pathways ◽  
Principal Component ◽  
Unsupervised Clustering ◽  
Survival Prediction ◽  
Multiple Perspectives ◽  
Single Cell Sequencing ◽  
Survival Expectations

Abstract Although substantial achievements in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) have led to fundamental improvements both in the basic research and clinical management, the potential mechanisms and regulatory relationships between m6A regulators and the TME are still unknown. We first conducted unsupervised clustering on the samples according to the core m6A expression, and then compared the signaling pathways, differential genes (DEGs), and TME between the m6A phenotypes, and re-validated the relationship between m6A regulators and TME by single cell sequencing. Then, the geneCluster was obtained by another unsupervised clustering of the DEGs, and the clinical as well as TME traits were evaluated among the geneClusters. Finally, the m6A scores of individual patients were calculated by principal component analysis (PCA) to verify the correlation from multiple perspectives, including survivals, clinical characters, mutations, TME, immunotherapy, and chemotherapy. Through a comprehensive analysis of 729 samples, we classified HCC patients into three m6A clusters and three geneClusters. Each group exhibited remarkable variations in terms of signaling pathways, clinical traits, and survival expectations. Notably, the m6A phenotypes corresponded to three different types of TME, namely immune-inflamed, immune-excluded, and immune-desert, respectively. In addition, the m6A regulator can accurately reflect the individualized microenvironment in HCC, and present supreme expression levels in the stromal microenvironment. However, the m6A score system is able to make accurate predictions not only in terms of clinical traits, survival prediction, and TME mentioned above, but also in the sensitivity of HCC patients to immunotherapy and chemotherapy. This study revealed the uniqueness and pluripotency of m6A regulators in the TME of HCC by combining single-cell sequencing and bulk sequencing. The quantified m6A modification indices were able to accurately predict patient survival expectations, clinical traits, TME, and sensitivity to immunotherapy and chemotherapy.

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