Severe hypertrophic cardiomyopathy in a patient with a homozygous MYH7 gene variant

Serra, Walter; Vitetta, Giulia; Uliana, Vera; Barocelli, Federico; Barili, Valeria; Allegri, Isabella; Ardissino, Diego; Gualandi, Francesca

doi:10.1016/j.heliyon.2022.e12373

Cited by 3 publications

(3 citation statements)

References 17 publications

(12 reference statements)

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“…To explore the potential role of HSPD1 in HNSCC, we systematically examined differentially expressed genes (DEGs) categorized by HSPD1 expression levels. Among the upregulated DEGs, MYH7 is associated with hypertrophic obstructive cardiomyopathy, and mutations in the MYH7 gene are linked to various myocardial diseases [33] . PAK5 is implicated in the development of multiple tumors; it enhances n-calmodulin trans-activation to promote metastasis in renal cell carcinoma [34] and contributes to cervical cancer progression through modi cations [35] .…”

Section: Knockdown Of Hspd1 Inhibits Hnscc Cell Growth In Vitromentioning

confidence: 99%

HSPD1 is a biomarker related to poor prognosis and tumor immune microenvironment in Head and Neck Squamous Cell Carcinoma by Bioinformatics and Cancer Database Analysis

Xu,

Zheng,

et al. 2024

Preprint

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Background: Heat shock protein D1 (HSPD1) is a molecular marker that is significantly highly expressed in numerous malignancies and plays a crucial role in assessing the prognostic status of patients.In the field of head and neck squamous cell carcinoma (HNSCC), the role of the HSPD1 gene in prognostic assessment and its potential link with immune cell infiltration remains largely unexplored, highlighting an urgent need for in-depth scientific research. Methods: In this study, we analyzed the expression data of the HSPD1 gene and its accompanying clinical information from The Cancer Genome Atlas (TCGA) database. The results showed that the expression level of the HSPD1 gene was significantly upregulated in most tumours compared to normal tissues. To validate this observation, we further verified it using Human Protein Atlas data. Through multivariate Cox regression analysis, we found that HSPD1 expression was significantly correlated with several clinicopathological features, suggesting that HSPD1 has the potential to act as an independent factor influencing the survival prognosis of HNSCC patients. Accordingly, we constructed a set of nomogram to more accurately predict the impact of HSPD1 expression on the prognosis of HNSCC patients. Meanwhile, we employed various tools, such as gene ontology analysis, gene set enrichment analysis (GSEA), single-sample GSEA, and the Tumour Immunoassessment Resource database, to explore in depth the biological roles of HSPD1 in HNSCC and its association with immune cell infiltration. Results: The mRNA and protein expression levels of HSPD1 were significantly increased in HNSCC tissues and cell lines. After Cox regression analysis, it was found that HNSCC patients with high HSPD1 expression had shorter overall survival (OS) than those with lower expression in both univariate and multivariate analyses, with statistically significant differences (p-value less than 0.05). In the assessment of the subject's work characteristics (ROC) curve, the area under the curve (AUC) of HSPD1 reached 0.846, showing high predictive accuracy.High expression of HSPD1 was strongly correlated with several clinicopathological features, including pathological N stage, histological grading, lymphovascular invasion, overall survival, and progression-free survival, and there was also a significant association with the patient's smoking history. Further functional enrichment analysis showed that HSPD1 plays an important role in tumourigenesis and cytochrome P450 metabolic pathway. Meanwhile, HSPD1 expression was positively correlated with NK CD56bright, helper T-cells (Th), and Th2 cells; and the infiltration of Mast cells, immature dendritic cells (iDC), Cytotoxic cells, Neutrophils, and mature dendritic cells (DC) was more pronounced in the low-expression group compared with the patients with high HSPD1 expression.Silencing HSPD1 reduced proliferation and migration in SCC9 and Cal27 cell lines. Conclusion: Elevated HSPD1 expression correlates with poor prognosis in HNSCC and impacts tumor immunity. It may function as an oncogene, influencing cell proliferation and migration. The findings highlight the need for in-depth academic research to determine the exact processes and functions.

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Section: Knockdown Of Hspd1 Inhibits Hnscc Cell Growth In Vitromentioning

confidence: 99%

HSPD1 is a biomarker related to poor prognosis and tumor immune microenvironment in Head and Neck Squamous Cell Carcinoma by Bioinformatics and Cancer Database Analysis

Xu,

Zheng,

et al. 2024

Preprint

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“…Gene dosage also affects prognosis in HCM [ 3 , 138 ]. Among HCM patients who exhibit two (digenic) or several (oligogenic) causal mutations in the same or different genes, the severity of ventricular hypertrophy appears to be more pronounced.…”

Section: Interconnections Of Genetic Basis and Outcomes In Hcmmentioning

confidence: 99%

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

2023

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Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype–phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.

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“…Although surgical treatment is possible, there is no perfect drug-based solution. Among patients with HCM and a pathogenic sarcomeric gene variant, 70% are involved in beta myosin heavy chain 7 (MYH7) and myosin-binding protein C3 (MYBPC3), whereas other genes ( MYL2, TNNI3, TNNT2, MYL3, ACTC1, TPM1 ) each account for a small proportion of patients (1–5%) ( 4 , 5 ). The precise mechanisms of HCM have not been fully analyzed.…”

Section: Introductionmentioning

confidence: 99%

SNHG 12 and hsa-miR-140-5P may play an important role in the ceRNA network related to hypertrophic cardiomyopathy

Zhai¹,

Guo²,

Zhou³

et al. 2023

J Thorac Dis

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Background: Competing endogenous RNA (ceRNA) networks play important roles in the mechanism and development of a variety of diseases. This study aimed to construct a ceRNA network of hypertrophic cardiomyopathy (HCM). Methods:We searched the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 353 samples to explore differentially expressed lncRNAs (DELs), microRNAs (miRNAs; DEMs), and messenger RNAs (DEmRNAs) during the progression of HCM. Weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and transcription factor (TF) prediction of miRNAs were also performed, and the GO terms, KEGG pathway terms, protein-protein interaction (PPI) network, and Pearson correlation network of the DEGs were visualized with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and through Pearson analysis. In addition, a ceRNA network related to HCM was constructed on the basis of the DELs, DEMs, and DEs. Finally, the function of the ceRNA network was explored via GO and KEGG enrichment analyses.Results: Through our analysis, 93 DELs (77 upregulated and 16 downregulated), 163 DEMs (91 upregulated and 72 downregulated), and 432 DEGs (238 upregulated and 194 downregulated) were screened.The functional enrichment analysis results for miRNAs showed that the miRNAs were mainly related to the VEGFR signaling network and the INFr pathway and were mainly regulated by TFs such as SOX1, TEAD1, and POU2F1. Gene set enrichment analysis (GSEA), GO analysis, and KEGG enrichment analysis showed that the DEGs were enriched in the Hedgehog signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a ceRNA network including 8 lncRNAs (e.g., LINC00324, SNHG12, and ALMS1-IT1), 7 miRNAs (e.g., hsa-miR-217, hsa-miR-184, and hsa-miR-140-5p), and 52 mRNAs (e.g., IGFBP5, TMED5, and MAGT1) was constructed. The results revealed that SNHG12, hsa-miR-140-5p, hsa-miR-217, TFRC, HDAC4, TJP1, IGFBP5, and CREB5 may form an important network involved in the pathology of HCM. Conclusions:The novel ceRNA network that we have demonstrated will provide new research points about molecular mechanisms of HCM.

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Severe hypertrophic cardiomyopathy in a patient with a homozygous MYH7 gene variant

Cited by 3 publications

References 17 publications

HSPD1 is a biomarker related to poor prognosis and tumor immune microenvironment in Head and Neck Squamous Cell Carcinoma by Bioinformatics and Cancer Database Analysis

HSPD1 is a biomarker related to poor prognosis and tumor immune microenvironment in Head and Neck Squamous Cell Carcinoma by Bioinformatics and Cancer Database Analysis

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers

SNHG 12 and hsa-miR-140-5P may play an important role in the ceRNA network related to hypertrophic cardiomyopathy

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