A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma

Chang, Kai-Tun; Wu, Hsing‐Ju; Liu, Chien-Wei; Lin, Hung‐Yu

doi:10.3390/ijms23042279

Cited by 8 publications

(4 citation statements)

References 44 publications

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“…Statistical comparisons were conducted as previously described [28]. Briefly, unpaired t-tests and one-way analyses of variance (ANOVA) were employed to analyze quantita-tive data of two-group and three-or-more-group comparisons, respectively.…”

Section: Discussionmentioning

confidence: 99%

Supervised Learning and Multi-Omics Integration Reveals Clinical Significance of Inner Membrane Mitochondrial Protein (IMMT) in Prognostic Prediction, Tumor Immune Microenvironment and Precision Medicine for Kidney Renal Clear Cell Carcinoma

Chen

Chu

Lin

2023

IJMS

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Kidney renal clear cell carcinoma (KIRC) accounts for approximately 75% of all renal cancers. The prognosis for patients with metastatic KIRC is poor, with less than 10% surviving five years after diagnosis. Inner membrane mitochondrial protein (IMMT) plays a crucial role in shaping the inner mitochondrial membrane (IMM), regulation of metabolism and innate immunity. However, the clinical relevance of IMMT in KIRC is not yet fully understood, and its role in shaping the tumor immune microenvironment (TIME) remains unclear. This study aimed to investigate the clinical significance of IMMT in KIRC using a combination of supervised learning and multi-omics integration. The supervised learning principle was applied to analyze a TCGA dataset, which was downloaded and split into training and test datasets. The training dataset was used to train the prediction model, while the test and the entire TCGA dataset were used to evaluate its performance. Based on the risk score, the cutoff between the low and high IMMT group was set at median value. A Kaplan-Meier curve, receiver operating characteristic (ROC) curve, principal component analysis (PCA) and Spearman’s correlation were conducted to evaluate the prediction ability of the model. Gene Set Enrichment Analysis (GSEA) was used to investigate the critical biological pathways. Immunogenicity, immunological landscape and single-cell analysis were performed to examine the TIME. Databases including Gene Expression Omnibus (GEO), Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were employed for inter-database verification. Pharmacogenetic prediction was analyzed via single-guide RNA (sgRNA)-based drug sensitivity screening using Q-omics v.1.30. Low expressions of IMMT in tumor predicted dismal prognosis in KIRC patients and correlated with KIRC progression. GSEA revealed that low expressions of IMMT were implicated in mitochondrial inhibition and angiogenetic activation. In addition, low IMMT expressions had associations with reduced immunogenicity and an immunosuppressive TIME. Inter-database verification corroborated the correlation between low IMMT expressions, KIRC tumors and the immunosuppressive TIME. Pharmacogenetic prediction identified lestaurtinib as a potent drug for KIRC in the context of low IMMT expressions. This study highlights the potential of IMMT as a novel biomarker, prognostic predictor and pharmacogenetic predictor to inform the development of more personalized and effective cancer treatments. Additionally, it provides important insights into the role of IMMT in the mechanism underlying mitochondrial activity and angiogenesis development in KIRC, which suggests IMMT as a promising target for the development of new therapies.

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Section: Discussionmentioning

confidence: 99%

Supervised Learning and Multi-Omics Integration Reveals Clinical Significance of Inner Membrane Mitochondrial Protein (IMMT) in Prognostic Prediction, Tumor Immune Microenvironment and Precision Medicine for Kidney Renal Clear Cell Carcinoma

Chen

Chu

Lin

2023

IJMS

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“…The potential mechanism of KCNQ1 underlying LUAD progression may lie in the perturbation of genes relevant to the cell cycle and DNA replication. However, KCNQ1-inhibitor gefitinib, which is the first-generation targeted therapy for non-small cell lung cancer, was implicated in the induction of heart QT prolongation in a guinea pig model, thereby raising a concern of arrhythmia when gefitinib is used for NSCLC treatment ( 80 ).…”

Section: Case Reportmentioning

confidence: 99%

Atrioventricular re-entrant tachycardia and atrioventricular node re-entrant tachycardia in a patient with cancer under chemotherapy: a case report and literature review

Dai,

Chen,

Qin

2024

Front. Cardiovasc. Med.

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Cardio-oncology is a new field of interest in cardiology focusing on the detection and treatment of cardiovascular diseases, such as arrhythmias, myocarditis, and heart failure, as side-effects of chemotherapy and radiotherapy. The association between chemotherapeutic agents and arrhythmias has previously been established. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. However, the association between chemotherapeutic agents and atrioventricular re-entrant tachycardia (AVRT)/atrioventricular node re-entrant tachycardia (AVNRT) remains poorly understood. Here, we report a patient with new-onset AVRT/AVNRT and lung cancer who underwent chemotherapy. We considered that chemotherapy or cancer itself may have been a trigger for the initiation of paroxysmal AVRT/AVNRT, and that radiofrequency catheter ablation was effective in treating this type of tachycardia. Here, possible mechanisms and potential genes (mostly ion channels) involved in AVRT/AVNRT are summarized and the mechanisms underlying the possible regulatory patterns of cancer cells and chemotherapy on ion channels are reviewed. Finally, we considered that ion channel abnormalities may link cancer or chemotherapy to the onset of AVRT/AVNRT. The aim of the present study was to highlight the association between chemotherapeutic agents and AVRT/AVNRT and to provide new insights for future research. Understanding the intermediate mechanisms between chemotherapeutic agents and AVRT/AVNRT may be beneficial in preventing chemotherapy-evoked AVRT/AVNRT (and/or other arrhythmias) in future.

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“…Among VGKC, different members (Kv1.3, Kv3.1, Kv3.4, Kv4.2, Kv5.1, Kv7.1, Kv9.3, Kv10.1, and Kv11.1) are involved in LC cell proliferation, migration and invasion ( Jang et al, 2011a ; Restrepo-Angulo et al, 2011 ; Glassmeier et al, 2012 ; Girault et al, 2014 ; Acuña-Macías et al, 2015 ; Lee et al, 2015 ; Chen et al, 2023 ) and some of them (Kv1.3, Kv4.2, and Kv7.1) have clinical relevance in NSCLC ( Girault et al, 2014 ; Lu X. et al, 2021 ; Chang et al, 2022 ; Angi et al, 2023 ) ( Table 4 ).…”

Section: Ion Channels In Human Cancermentioning

confidence: 99%

Ion channels in lung cancer: biological and clinical relevance

Capitani,

Chioccioli Altadonna,

Santillo

et al. 2023

Front. Pharmacol.

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Despite improvements in treatment, lung cancer is still a major health problem worldwide. Among lung cancer subtypes, the most frequent is represented by adenocarcinoma (belonging to the Non-Small Cell Lung Cancer class) although the most challenging and harder to treat is represented by Small Cell Lung Cancer, that occurs at lower frequency but has the worst prognosis. For these reasons, the standard of care for these patients is represented by a combination of surgery, radiation therapy and chemotherapy. In this view, searching for novel biomarkers that might help both in diagnosis and therapy is mandatory. In the last 30 years it was demonstrated that different families of ion channels are overexpressed in both lung cancer cell lines and primary tumours. The altered ion channel profile may be advantageous for diagnostic and therapeutic purposes since most of them are localised on the plasma membrane thus their detection is quite easy, as well as their block with specific drugs and antibodies. This review focuses on ion channels (Potassium, Sodium, Calcium, Chloride, Anion and Nicotinic Acetylcholine receptors) in lung cancer (both Non-Small Cell Lung Cancer and Small Cell Lung Cancer) and recapitulate the up-to-date knowledge about their role and clinical relevance for a potential use in the clinical setting, for lung cancer diagnosis and therapy.

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A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma

Cited by 8 publications

References 44 publications

Supervised Learning and Multi-Omics Integration Reveals Clinical Significance of Inner Membrane Mitochondrial Protein (IMMT) in Prognostic Prediction, Tumor Immune Microenvironment and Precision Medicine for Kidney Renal Clear Cell Carcinoma

Supervised Learning and Multi-Omics Integration Reveals Clinical Significance of Inner Membrane Mitochondrial Protein (IMMT) in Prognostic Prediction, Tumor Immune Microenvironment and Precision Medicine for Kidney Renal Clear Cell Carcinoma

Atrioventricular re-entrant tachycardia and atrioventricular node re-entrant tachycardia in a patient with cancer under chemotherapy: a case report and literature review

Ion channels in lung cancer: biological and clinical relevance

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