BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma

BackgroundAs a crucial constituent part of Polycomb repressive complex 2, PHD finger protein 19 (PHF19) plays a pivotal role in epigenetic regulation, and acts as a critical regulator of multiple pathophysiological processes. However, the exact roles of PHF19 in cancers remain enigmatic. The present research was primarily designed to provide the prognostic landscape visualizations of PHF19 in cancers, and study the correlations between PHF19 expression and immune infiltration characteristics in tumor microenvironment.MethodsRaw data in regard to PHF19 expression were extracted from TCGA and GEO data portals. We examined the expression patterns, prognostic values, mutation landscapes, and protein-protein interaction network of PHF19 in pan-cancer utilizing multiple databases, and investigated the relationship of PHF19 expression with immune infiltrates across TCGA-sequenced cancers. The R language was used to conduct KEGG and GO enrichment analyses. Besides, we built a risk-score model of hepatocellular carcinoma (HCC) and validated its prognostic classification efficiency.ResultsOn balance, PHF19 expression was significantly higher in cancers in comparison with that in noncancerous samples. Increased expression of PHF19 was detrimental to the clinical prognoses of cancer patients, especially HCC. There were significant correlations between PHF19 expression and TMB or MSI in several cancers. High PHF19 levels were critically associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that PHF19 participated in regulating carcinogenic processes including cell cycle and DNA replication, and was correlated with the progression of HCC. Intriguingly, GSEA suggested that PHF19 was correlated with the cellular components including immunoglobulin complex and T cell receptor complex in HCC. Based on PHF19-associated functional gene sets, an eleven-gene prognostic signature was constructed to predict HCC prognosis. Finally, we validated pan-cancer PHF19 expression, and its impacts on immune infiltrates in HCC.ConclusionThe epigenetic related regulator PHF19 participates in the carcinogenic progression of multiple cancers, and may contribute to the immune infiltration in tumor microenvironment. Our study suggests that PHF19 can serve as a carcinogenic indicator related to prognosis in pan-cancer, especially HCC, and shed new light on therapeutics of cancers for clinicians.

Download Full-text

Profiles of immune infiltration in the tumor microenvironment of hepatocellular carcinoma

Journal of Gastrointestinal Oncology ◽

10.21037/jgo-21-291 ◽

2021 ◽

Vol 0 (0) ◽

pp. 1161-1172

Author(s):

Lei Meng ◽

Rulan Ma ◽

Rong Yan ◽

Dawei Yuan ◽

Yijun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Immune Infiltration

Download Full-text

8DEstablishment and validation of a hypoxia-related signature predicting prognosis in hepatocellular carcinoma

BMC Gastroenterology ◽

10.1186/s12876-021-02057-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Congbo Cai ◽

Lei Yang ◽

Kena Zhou

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Prognostic Factor ◽

Tumor Microenvironment ◽

Crucial Role ◽

Prognostic Model ◽

Immune Infiltration ◽

Risk Patients ◽

Immunosuppressive Microenvironment

Abstract Background Hypoxia plays a crucial role in immunotherapy of hepatocellular carcinoma (HCC) by changing the tumor microenvironment. Until now the association between hypoxia genes and prognosis of HCC remains obscure. We attempt to construct a hypoxia model to predict the prognosis in HCC. Results We screened out 3 hypoxia genes (ENO1, UGP2, TPI1) to make the model, which can predict prognosis in HCC. And this model emerges as an independent prognostic factor for HCC. A Nomogram was drawn to evaluate the overall survival in a more accurate way. Furthermore, immune infiltration state and immunosuppressive microenvironment of the tumor were detected in high-risk patients. Conclusion We establish and validate a risk prognostic model developed by 3 hypoxia genes, which could effectively evaluate the prognosis of HCC patients. This prognostic model can be used as a guidance for hypoxia modification in HCC patients undergoing immunotherapy.

Download Full-text

Status and Development of The Tumor Microenvironment in Hepatocellular Carcinoma*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2011.00383 ◽

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

Download Full-text

Transcriptional Landscape of PD-1, PD-L1 and PD-L2 Correlated Genes and Their Association with Mutation, Immune Infiltration and Clinical Outcomes of Hepatocellular Carcinoma

SSRN Electronic Journal ◽

10.2139/ssrn.3429886 ◽

2019 ◽

Author(s):

Qiuju Sheng ◽

Xiaoguang Dou ◽

Chong Zhang ◽

Yanwei Li ◽

Chao Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Outcomes ◽

Immune Infiltration ◽

Transcriptional Landscape

Download Full-text

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

Medicina ◽

10.3390/medicina57020131 ◽

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.

Download Full-text

Metabolic reprogramming of immune cells: Shaping the tumor microenvironment in hepatocellular carcinoma

Cancer Medicine ◽

10.1002/cam4.4177 ◽

2021 ◽

Author(s):

Yujia Xia ◽

Zachary J. Brown ◽

Hai Huang ◽

Allan Tsung

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Immune Cells ◽

Metabolic Reprogramming

Download Full-text

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

Journal of Personalized Medicine ◽

10.3390/jpm11030219 ◽

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.

Download Full-text