Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation

Ke, Mengyun; Xu, Tao; Fang, Yi; Ye, Yuanpeng; Li, Zhi-jin; Ren, Fenggang; Lu, Shaoying; Zhang, Xufeng; Wu, Rongqian; Lv, Yi; Dong, Jian

doi:10.1016/j.canlet.2021.05.007

Cited by 27 publications

(21 citation statements)

References 35 publications

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“…To further improve the reliability and clinical utility of this prognostic As an essential immune organ in the human body, the canceration of the liver means the dysregulation of its immune regulation mechanism, which may lead to immune tolerance and immune evasion of tumors. [32][33][34] In addition, tumor immunosuppression in the liver has an important impact on the development and progression of HCC. [35] Therefore, developing effective immunotherapy against HCC is very challenging.…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

Liu

et al. 2023

Medicine

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Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. The long non-coding RNA (lncRNA) has been found to have great potential as a prognostic biomarker or therapeutic target for cancer patients. However, the prognostic value and tumor immune infiltration of lncRNAs in HCC has yet to be fully elucidated. To identify prognostic biomarkers of lncRNA in HCC by integrated bioinformatics analysis and explore their functions and relationship with tumor immune infiltration. The prognostic risk assessment model for HCC was constructed by comprehensively using univariate/multivariate Cox regression analysis, Kaplan–Meier survival analysis, and the least absolute shrinkage and selection operator regression analysis. Subsequently, the accuracy, independence, and sensitivity of our model were evaluated, and a nomogram for individual prediction in the clinic was constructed. Tumor immune microenvironment (TIME), immune checkpoints, and human leukocyte antigen alleles were compared in high- and low-risk patients. Finally, the functions of our lncRNA signature were examined using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and gene set enrichment analysis. A 6-lncRNA panel of HCC consisting of RHPN1-AS1, LINC01224, CTD-2510F5.4, RP1-228H13.5, LINC01011, and RP11-324I22.4 was eventually identified, and show good performance in predicting the survivals of patients with HCC and distinguishing the immunomodulation of TIME of high- and low-risk patients. Functional analysis also suggested that this 6-lncRNA panel may play an essential role in promoting tumor progression and immune regulation of TIME. In this study, 6 potential lncRNAs were identified as the prognostic biomarkers in HCC, and the regulatory mechanisms involved in HCC were initially explored.

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Section: Discussionmentioning

confidence: 99%

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

Liu

et al. 2023

Medicine

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“…9,10,20,38,40,41 Elevated GOLM1 levels have also been reported in other liver pathologies, specifically non-alcoholic steatohepatitis and alcoholic liver disease. 42 The higher expression of GOLM1 is associated with decreased survival in lung cancer, melanoma, colorectal cancer, uveal melanoma and HCC. 29,40,43,44 As recently reviewed elsewhere, 9 GOLM1 expression can be increased by multiple extracellular factors in the tumor microenvironment, including hypoxia, 22 various miRNAs, [45][46][47] and the cytokines IL-1b, 48 IL-6 and Oncostatin M. 49 However, the upregulation of GOLM1 is not a universal phenomenon in cancer, because lower levels of GOLM1 have been reported in colon cancer.…”

Section: Golm1 Affects Cytokines In Cancermentioning

confidence: 99%

“…First, elevated levels of GOLM1 increase cell surface recycling of the EGFR, 20 which in turn increases EGFR signaling and thereby promotes immune escape by elevating the expression of the immune checkpoint ligand PD-L1. 42 Similarly, GOLM1 mediates cell surface recycling of RTKs and thereby affects the expression of cancer-related proteins downstream of RTK signaling, including E-cadherin and the metalloprotease MMP9. 20 GOLM1 also directly regulates the trafficking of the other metalloproteases MMP2 and MMP7 through the Golgi network, as knockdown of GOLM1 induces their intracellular accumulation.…”

Section: Golm1 Affects Cytokines In Cancermentioning

confidence: 99%

“…However, GOLM1 protein and mRNA levels are also increased in other, non‐virally induced cancer types, for example lung cancer, prostate cancer, gastric cancer, melanoma, breast cancer and testicular cancer 9,10,20,38,40,41 . Elevated GOLM1 levels have also been reported in other liver pathologies, specifically non‐alcoholic steatohepatitis and alcoholic liver disease 42 . The higher expression of GOLM1 is associated with decreased survival in lung cancer, melanoma, colorectal cancer, uveal melanoma and HCC 29,40,43,44 .…”

Section: Golm1 Affects Cytokines In Cancermentioning

confidence: 99%

“…However, most described mechanisms relate to a role of GOLM1 in organelle trafficking. First, elevated levels of GOLM1 increase cell surface recycling of the EGFR, 20 which in turn increases EGFR signaling and thereby promotes immune escape by elevating the expression of the immune checkpoint ligand PD‐L1 42 . Similarly, GOLM1 mediates cell surface recycling of RTKs and thereby affects the expression of cancer‐related proteins downstream of RTK signaling, including E‐cadherin and the metalloprotease MMP9 20 .…”

Section: Golm1 Affects Cytokines In Cancermentioning

confidence: 99%

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Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

et al. 2023

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The Golgi membrane protein GOLM1/GP73/GOLPH2 has been found to impact cytokine production in both infectious disease and cancer. In viral infections, GOLM1 levels are increased, and this lowers the production of type I interferons and other inflammatory cytokines. However, elevated GOLM1 expression levels due to mutations are linked to a higher production of interleukin (IL)‐6 during Candida infections, potentially explaining an increased susceptibility to candidemia in individuals carrying these mutations. In cancer, the protease Furin produces a soluble form of GOLM1 that has oncogenic properties by promoting the production of the chemokine CCL2 and suppressing the production of inflammatory cytokines such as IL‐12 and interferon gamma. This review will focus on the role of GOLM1 in cytokine production, highlighting how it can both promote and inhibit cytokine production. It is crucial to understand this in order to effectively target GOLM1 for therapeutic purposes in diseases associated with abnormal cytokine production, including cancer and infectious disease.

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Fibrosis and Immunotherapy in Hepatocellular Carcinoma

White

Maddirela

2023

Interdisciplinary Cancer Research

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Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation

Cited by 27 publications

References 35 publications

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis

Unveiling the impact of GOLM1/GP73 on cytokine production in cancer and infectious disease

Fibrosis and Immunotherapy in Hepatocellular Carcinoma

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