Human Hepatic Cancer Stem Cells (HCSCs) Markers Correlated With Immune Infiltrates Reveal Prognostic Significance of Hepatocellular Carcinoma

Sang, Xiaopu; Wu, Fenfang; Wu, Di; Lin, Shan; Li, Jingyi; Zhao, Nan; Chen, Xiaoni; Xu, Anlong

doi:10.3389/fgene.2020.00112

Cited by 16 publications

(11 citation statements)

References 56 publications

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“…Yet another A1CF target, Sox9 mRNA, which was immunoprecipitated from hepatocytes from A1cf +/Tg mice, was identified as a hepatic stem cell marker in HCC with SOX9 overexpression in patients correlating with reduced overall survival (47).…”

Section: Discussionmentioning

confidence: 99%

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

Blanc¹,

Riordan²,

Soleyman-Jahi³

et al. 2021

Journal of Clinical Investigation

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RNA binding protein Apobec1 Complementation Factor (A1CF) regulates posttranscriptional ApoB mRNA editing but the range of RNA targets and long-term impact of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf transgenic (A1cf +/Tg), A1cf +/Tg Apobec1-/and A1cf-/mice fed chow or high fat/high fructose diets using RNA-Seq, RNA-CLIP Seq and tissue microarrays from human hepatocellular cancer (HCC). A1cf +/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf +/Tg mice developed spontaneous fibrosis, dysplasia and HCC, which was accelerated on a high fat/fructose diet and independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfa, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), proliferation (Kif20a, Mcm2, Mcm4, Mcm6) with a subset of mRNAs (including Sox4, Sox9, Cdh1) identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. In conclusion, we show that hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative and inflammatory pathways leading to HCC.

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Section: Discussionmentioning

confidence: 99%

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

Blanc¹,

Riordan²,

Soleyman-Jahi³

et al. 2021

Journal of Clinical Investigation

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“…Tumor microenvironment (TME) contributes largely to the development of tumor heterogeneity and the development of tumors [ 18 ]. In the TME, immune infiltration patterns are valuable for prognostic assessment in HCC [ 19 ]. The interdependent relationship between tumor metabolism and immune infiltration has been reported in previous studies as well [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a glycolysis-associated multiomics prognostic model for hepatocellular carcinoma

Deng

Jin

et al. 2021

Aging

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Increased glycolysis has been reported as a major metabolic hallmark in many cancers, and is closely related to malignant behavior of tumors. However, the potential mechanism of glycolysis in hepatocellular carcinoma (HCC) and its prognostic value are not well understood. To address this, we investigated glycolysis-related gene expression data of patients with HCC from TCGA and ICGC. Patients were categorized into three different glycolysis-associated subgroups: Glycolysis-M, Glycolysis-H, and Glycolysis-L. We found that Glycolysis-H combined with Glycolysis-M (Glycolysis-H+M) subgroup was associated with poor overall survival and distinct cancer stem cell characteristics and immune infiltrate patterns. Additionally, multiomics-based analyses were conducted to evaluate genomic patterns of glycolysis subgroups, including their gene mutations, copy number variations, and RNA-sequencing data. Finally, a glycolysis-associated multiomics prognostic model (GMPM) consisting of 19 glycolysis-associated genes was developed. The capability of GMPM in categorizing patients with HCC into high- and low-risk groups was validated with independent HCC datasets. Finally, GMPM was confirmed as an independent risk factor for the prognosis of patients with HCC. We believe that our findings provide new insights into the mechanism of glycolysis and highlight the potential clinical value of GMPM in predicting the prognosis of patients with HCC.

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“…It has been shown that the expression of CSC makers in human tumor tissues is correlated with the number of tumor-infiltrating immune cells [ 34 , 35 ], suggesting that CSCs exhibit a close relationship with the tumor immune environment. Accumulating evidence suggests that the immune response to CSCs is frequently compromised because of their immune evasion properties.…”

Section: Immunosuppressive Properties Endowed On Cscsmentioning

confidence: 99%

Immune evasion by cancer stem cells

Tsuchiya

Shiota

2021

Regenerative Therapy

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Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies.

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Human Hepatic Cancer Stem Cells (HCSCs) Markers Correlated With Immune Infiltrates Reveal Prognostic Significance of Hepatocellular Carcinoma

Cited by 16 publications

References 56 publications

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

Identification and validation of a glycolysis-associated multiomics prognostic model for hepatocellular carcinoma

Immune evasion by cancer stem cells

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