Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis

Huang, Juanjun; Lin, Jing; Chen, Xiaoli; Zhu, Wei

doi:10.1097/md.0000000000027739

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…Huang et al [36] and Gururaja et al [37] noticed an association between CLIC1 and CLIC 3 immunoexpression and an advanced state of HCC and survival in several different cancers. In the present study, the highest survival rate was found in patients with the desmoplastic and pushing type of LM, with CLIC1 scores of 3 and Avastin treatment.…”

Section: Discussionmentioning

confidence: 99%

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin

Ceauşu

Ciolofan

Blidișel

et al. 2023

CIMB

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Chloride intracellular channel 1 (CLIC1) is involved in cell migration and metastasis. The histological growth patterns of liver metastasis are as follows: desmoplastic (d-HGP), replacement (r-HGP), pushing (p-HGP), and mixed. The aim of this study was to evaluate the relation between HGP, angiogenesis, and CLIC1 expression. Materials and Methods: A total of 40 cases of primary tumors and their LM: d-HGP (12 cases), r-HGP (13 cases), and p-HGP (15 cases), were evaluated through simple and double immunostaining. CLIC1 assessment was conducted as follows: scores of 0 (less than 10% of positive cells), 1 (10–30%), 2 (30–50%), or 3 (more than 50%) were assigned. Heterogeneous CLIC1 expression was found. CLIC1 in primary tumors correlated with grade G for all cases of LM with a p-HGP (p = 0.004). The CLIC1 score for LMs with an r-HGP correlated with grade G of the corresponding primary tumor (p = 0.027). CLIC1 and CD34+/Ki67+ vessels (p = 0.006) correlated in primary tumors. CLIC1 in primary tumors correlated with CD34+/Ki67+ vessels of LMs with a d HGP (p = 0.024). Conclusions: The CLIC1 score may have prognostic value, mainly for LMs with a p-HGP and r-HGP, and therapeutic value for LMs with a d-HGP.

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Section: Discussionmentioning

confidence: 99%

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin

Ceauşu

Ciolofan

Blidișel

et al. 2023

CIMB

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“…AAK1 is involved in clathrin-mediated endocytosis of chemokine receptors and AAK1-inhibition in mice resulted in increased intratumoral infiltration, supporting an immune-suppressive role for this gene product, as well [ 26 ]. CLIC3 is a chloride intracellular channel protein the gene expression of which has been correlated with low immune infiltration of myeloid dendritic cells (DCs) and poor prognosis in hepatocellular carcinoma [ 27 ]. Therefore, it is possible that a similar immune suppressive role could be exerted in HIF-2-altered UC.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

et al. 2022

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Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-preventing genes.

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“…CLICs are a family of multifunctional proteins that can have diverse functions, including chloride transport or the regulation and modulation of gene expression or cytoskeleton structure [206,240]. Intracellular chloride channels are also involved in neurological, pulmonary, and cardiovascular functions and are related to pathologies such as cancer, as they regulate cell cycle and apoptosis [238,241,242].…”

Section: Chloride Intracellular Channels (Clics)mentioning

confidence: 99%

Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers

Chiliquinga,

Acosta,

Ogonaga-Borja

et al. 2023

Cells

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The human papilloma virus (HPV) group comprises approximately 200 genetic types that have a special affinity for epithelial tissues and can vary from producing benign symptoms to developing into complicated pathologies, such as cancer. The HPV replicative cycle affects various cellular and molecular processes, including DNA insertions and methylation and relevant pathways related to pRb and p53, as well as ion channel expression or function. Ion channels are responsible for the flow of ions across cell membranes and play very important roles in human physiology, including the regulation of ion homeostasis, electrical excitability, and cell signaling. However, when ion channel function or expression is altered, the channels can trigger a wide range of channelopathies, including cancer. In consequence, the up- or down-regulation of ion channels in cancer makes them attractive molecular markers for the diagnosis, prognosis, and treatment of the disease. Interestingly, the activity or expression of several ion channels is dysregulated in HPV-associated cancers. Here, we review the status of ion channels and their regulation in HPV-associated cancers and discuss the potential molecular mechanisms involved. Understanding the dynamics of ion channels in these cancers should help to improve early diagnosis, prognosis, and treatment in the benefit of HPV-associated cancer patients.

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Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis

Abstract: Supplemental Digital Content is available in the text

Cited by 7 publications

References 41 publications

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers

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