Ion Channels in Lung Cancer

Bulk, Etmar; Todesca, Luca Matteo; Schwab, Albrecht

doi:10.1007/112_2020_29

Cited by 13 publications

(7 citation statements)

References 116 publications

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“…Reviews from recent years on the role of ion channels in cancer ( Djamgoz et al, 2014 ; Klumpp et al, 2018 ; Prevarskaya et al, 2018 ; Bulk et al, 2020 ; Ling and Kalthoff, 2020 ; Schnipper et al, 2020 ) predominantly focused on how ion channels shape the aggressive cancer cell behavior. However, cancer must be viewed as a complex tissue composed of different cell types.…”

Section: Introductionmentioning

confidence: 99%

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

et al. 2021

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Pancreatic ductal adenocarcinoma is a devastating disease with a dismal prognosis. Therapeutic interventions are largely ineffective. A better understanding of the pathophysiology is required. Ion channels contribute substantially to the “hallmarks of cancer.” Their expression is dysregulated in cancer, and they are “misused” to drive cancer progression, but the underlying mechanisms are unclear. Ion channels are located in the cell membrane at the interface between the intracellular and extracellular space. They sense and modify the tumor microenvironment which in itself is a driver of PDAC aggressiveness. Ion channels detect, for example, locally altered proton and electrolyte concentrations or mechanical stimuli and transduce signals triggered by these microenvironmental cues through association with intracellular signaling cascades. While these concepts have been firmly established for other cancers, evidence has emerged only recently that ion channels are drivers of PDAC aggressiveness. Particularly, they appear to contribute to two of the characteristic PDAC features: the massive fibrosis of the tumor stroma (desmoplasia) and the efficient immune evasion. Our critical review of the literature clearly shows that there is still a remarkable lack of knowledge with respect to the contribution of ion channels to these two typical PDAC properties. Yet, we can draw parallels from ion channel research in other fibrotic and inflammatory diseases. Evidence is accumulating that pancreatic stellate cells express the same “profibrotic” ion channels. Similarly, it is at least in part known which major ion channels are expressed in those innate and adaptive immune cells that populate the PDAC microenvironment. We explore potential therapeutic avenues derived thereof. Since drugs targeting PDAC-relevant ion channels are already in clinical use, we propose to repurpose those in PDAC. The quest for ion channel targets is both motivated and complicated by the fact that some of the relevant channels, for example, KCa3.1, are functionally expressed in the cancer, stroma, and immune cells. Only in vivo studies will reveal which arm of the balance we should put our weights on when developing channel-targeting PDAC therapies. The time is up to explore the efficacy of ion channel targeting in (transgenic) murine PDAC models before launching clinical trials with repurposed drugs.

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Section: Introductionmentioning

confidence: 99%

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

et al. 2021

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“…PD-1/PDL-1 monoclonal antibody-based ICI therapy has emerged as a new treatment option for advanced HNSCC. Several tumors, including lung carcinoma ( 39 ), prostate carcinoma ( 40 ), colon carcinoma ( 41 ), and glioblastoma ( 42 ), have recently been found to express ion channel genes to varying degrees. It has been demonstrated that increased ion channel expression promotes malignant tumor progression.…”

Section: Discussionmentioning

confidence: 99%

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance

et al. 2022

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PurposeHead and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients.MethodsClinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry.ResultsWe separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments.ConclusionThe 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.

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“…Aberrant activation of these coregulators can drive different stages of cancer progression, including tumor invasion, cell spread, and metastatic colonization and growth [45] e ion (such as Ca 2+ , K + , Fe 3+ , and Cl − ) and channel proteins play important roles in tumor progression. ese membrane ion transport systems have great potential as diagnostic biomarkers and therapeutic targets in tumor treatment [46][47][48]. GTPase-related signaling pathways are widely abnormally activated in tumors and are involved in the regulation of tumor cell growth, metastasis, and drug resistance [49].…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

Sun

et al. 2022

International Journal of Endocrinology

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Background. Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism. Although numerous studies have studied the subject, the predictive value of gene biomarkers nevertheless remains low. Methods. In this study, we performed genomic analysis of abnormal DNA methylation in parathyroid tumors. After data preprocessing, differentially methylated genes were extracted from patients with parathyroid tumors by using t-tests. Results. After refinement of the basic differential methylation, 28241 unique CpGs (634 genes) were identified to be methylated. The methylated genes were primarily involved in 7 GO terms, and the top 3 terms were associated with cyst morphogenesis, ion transport, and GTPase signal. Following pathway enrichment analyses, a total of 10 significant pathways were enriched; notably, the top 3 pathways were cholinergic synapses, glutamatergic synapses, and oxytocin signaling pathways. Based on PPIN and ego-net analysis, 67 ego genes were found which could completely separate the diseased group from the normal group. The 10 most prominent genes included POLA1, FAM155 B, AMMECR1, THOC2, CCND1, CLDN11, IDS, TST, RBPJ, and GNA11. SVM analysis confirmed that this grouping approach was precise. Conclusions. This research provides useful data to further explore novel genes and pathways as therapeutic targets for parathyroid tumors.

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Ion Channels in Lung Cancer

Cited by 13 publications

References 116 publications

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

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