&lt;p&gt;Effects of LRP1B Regulated by HSF1 on Lipid Metabolism in Hepatocellular Carcinoma&lt;/p&gt;

Li, Miaomiao; Hu, Juntao; Jin, Riming; Cheng, Hongxia; Liu, Limin; Guo, Kun

doi:10.2147/jhc.s279123

Cited by 20 publications

(14 citation statements)

References 54 publications

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“…So far, Guo et al used both CRISPR-Cas9 silencing and CRISPRa transcription activation systems to, respectively, downregulate and upregulate LRP1B expression in hepatocellular carcinoma cells (HCC). In this study, in contrast to what is mostly reported for cancer cells, LRP1B expression is predominantly strong [ 107 ]. This study presented a unique role for LRP1B in this setting, as a mediator in lipid metabolism, and further proposes LRP1B-mediated lipid metabolism as a potential therapeutic strategy for HCC in the future [ 107 ].…”

Section: Lrp1b Impairment In Cancercontrasting

confidence: 79%

“…In this study, in contrast to what is mostly reported for cancer cells, LRP1B expression is predominantly strong [ 107 ]. This study presented a unique role for LRP1B in this setting, as a mediator in lipid metabolism, and further proposes LRP1B-mediated lipid metabolism as a potential therapeutic strategy for HCC in the future [ 107 ].…”

Section: Lrp1b Impairment In Cancercontrasting

confidence: 79%

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LRP1B: A Giant Lost in Cancer Translation

et al. 2021

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Low-density lipoprotein receptor-related protein 1B (LRP1B) is a giant member of the LDLR protein family, which includes several structurally homologous cell surface receptors with a wide range of biological functions from cargo transport to cell signaling. LRP1B is among the most altered genes in human cancer overall. Found frequently inactivated by several genetic and epigenetic mechanisms, it has mostly been regarded as a putative tumor suppressor. Still, limitations in LRP1B studies exist, in particular associated with its huge size. Therefore, LRP1B expression and function in cancer remains to be fully unveiled. This review addresses the current understanding of LRP1B and the studies that shed a light on the LRP1B structure and ligands. It goes further in presenting increasing knowledge brought by technical and methodological advances that allow to better manipulate LRP1B expression in cells and to more thoroughly explore its expression and mutation status. New evidence is pushing towards the increased relevance of LRP1B in cancer as a potential target or translational prognosis and response to therapy biomarkers.

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Section: Lrp1b Impairment In Cancercontrasting

confidence: 79%

Section: Lrp1b Impairment In Cancercontrasting

confidence: 79%

LRP1B: A Giant Lost in Cancer Translation

et al. 2021

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“…Based on the sequencing data of liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 657 liver tumors from Chinese clinical dataset, Wang and his colleagues claimed that LRP1B contributed to 12.3% of HCC patients with mutated gene in the Chinese cohort [20] , which is similar to the results here (shown as Figure 1A). Meanwhile, they also suggested that the LRP1B mutations were significantly associated with shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012), as a poor prognostic factor in HCC.…”

Section: Discussionsupporting

confidence: 79%

Development and validation of LRP1B mutation-associated prognostic model for hepatocellular carcinoma

Shen

Zhang

et al. 2021

Bioscience Reports

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Purpose: To develop a LRP1B gene mutation based prognostic model for hepatocellular carcinoma (HCC) patients risk prediction. Methods: The LRP1B gene mutation rate was calculated from HCC patient samples. Meanwhile, differentially expressed genes according to LRP1B mutant were screened out for prognostic model establishment. Based on this innovative model, HCC patients were categoried into high and low-risk group. The immune status including immune cell infiltration ratio and checkpoints have been explored in two groups. The functions of LRP1B and risk factors in the model were verified using both in vivo and in vitro experiments. Results: It could be demonstrated that LRP1B was a potential negative predictor for HCC patients prognosis with high mutation frequency. The functions of LRP1B was verified with ELISA assay and Quantitative Real-time PCR method based on clinical recruited HCC participants. 11 genes displayed significant differences according to LRP1B status, which could better predict HCC patient prognosis. The functions of these genes were examined using HCC cell line HCCLM3, suggesting they played a pivotal role in determining HCC cell proliferation and apoptosis. From the immune cell infiltration ratio analysis, there was a significant difference in the infiltration degree of 7 types of immune cells and 2 immune checkpoints between high and low-risk HCC patients. Conclusion: This study hypothesized a potential prognostic biomarker and developed a novel LRP1B mutation-associated prognostic model for hepatocellular carcinoma, which provided a systematic reference for future understanding of clinical research.

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“… 10 , 11 Moreover, LRP1B mutations are associated with favorable outcomes to ICI treatment of multiple cancer types. 12 LRP1B serves as a mediator of lipid metabolism in HCC, 13 and is one of 20 recurrent hepatitis B virus (HBV) targeted genes in HBV infected HCC patients. 14 However, knowledge about the relationship between LRP1B and HCC prognosis remains limited.…”

Section: Introductionmentioning

confidence: 99%

LRP1B is a Potential Biomarker for Tumor Immunogenicity and Prognosis of HCC Patients Receiving ICI Treatment

Cheng

Tang

et al. 2022

JHC

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Background New predictors of the efficacy of hepatocellular carcinoma (HCC) immunotherapy are needed. The ability of a single gene mutation to predict the therapeutic effect of immune checkpoint inhibitors (ICI) in HCC remains unknown. Methods The most frequently mutated genes in HCC were analyzed using the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Mutant genes that correlated with the tumor mutational burden (TMB) and prognosis were obtained. The mutation pattern and immunological function of one of the most frequently mutated genes, LRP1B, were determined. A pan-tumor analysis of LRP1B expression, association with cancer prognosis, and immunological role was also explored. A retrospective clinical study was conducted using 102 HCC patients who received ICI treatment to further verify whether gene mutations can predict the effectiveness of immunotherapy and prognosis of HCC. Results LRP1B is among the most frequently mutated genes in HCC cohorts in TCGA and ICGC datasets. TCGA data showed that the LRP1B mutation activated immune signaling pathways and promoted mast cell activation. Patients with LRP1B mutations had significantly higher TMB than those with wild-type LRP1B. LRP1B expression correlated with the cancer-immunity cycle and immune cell infiltration. High LRP1B expression was also associated with poor survival among HCC patients. Results from the clinical study showed that HCC patients in the LRP1B mutation group had a poor response to ICI and worse prognosis than the wild-type group. The LRP1B mutation group had significantly higher TMB and mast cell infiltration in tumor tissues. Conclusion This study is the first to report that a single gene LRP1B mutation is associated with a poor clinical response to ICI treatment and negative outcomes in HCC patients. HighLRP1B expression correlated with tumor immunity and HCC prognosis.

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<p>Effects of LRP1B Regulated by HSF1 on Lipid Metabolism in Hepatocellular Carcinoma</p>

Cited by 20 publications

References 54 publications

LRP1B: A Giant Lost in Cancer Translation

LRP1B: A Giant Lost in Cancer Translation

Development and validation of LRP1B mutation-associated prognostic model for hepatocellular carcinoma

LRP1B is a Potential Biomarker for Tumor Immunogenicity and Prognosis of HCC Patients Receiving ICI Treatment

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