Genetic expression in cancer research: Challenges and complexity

Gene Reports, Journal Year: 2024, Volume and Issue: unknown, P. 102042 - 102042

Published: Sept. 1, 2024

Language: Английский

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Is the voltage-gated sodium channel β3 subunit (SCN3B) a biomarker for glioma?

Functional & Integrative Genomics, Journal Year: 2024, Volume and Issue: 24(5)

Published: Sept. 18, 2024

Language: Английский

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Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314745 - e0314745

Published: Jan. 16, 2025

Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark cancer is ability to sustain proliferative signaling, which closely tied various cell cycle processes. Centromere Protein (CENPA), a variant standard histone H3, crucial for selective chromosome segregation during cycle. Despite its importance, comprehensive pan-cancer bioinformatic analysis CENPA has not yet been conducted. Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA's genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across populations cellular locations, link cycle, impact survival, relationship immune microenvironment. Additionally, prognostic model glioma patients was developed demonstrate potential as biomarker. Furthermore, drugs targeting in cells identified predicted using drug sensitivity correlations protein-ligand docking. exhibited low levels gene mutation cancers. It found be overexpressed nearly all types TCGA, relative normal controls, predominantly located nucleus malignant cells. showed strong particularly biomarker G2 phase. also emerged valuable diagnostic multiple types. In glioma, demonstrated reliable when used alongside other factors. linked Drugs such CD-437, 3-Cl-AHPC, Trametinib, BI-2536, GSK461364 target serves cancers, offering both value.

Language: Английский

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ADME gene-driven prognostic model for bladder cancer: a breakthrough in predicting survival and personalized treatment

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 19, 2025

Abstract Background Genes that participate in the absorption, distribution, metabolism, excretion (ADME) processes occupy a central role pharmacokinetics. Meanwhile, variability clinical outcomes and responses to treatment is notable bladder cancer (BLCA). Methods Our study utilized expansive datasets from TCGA GEO explore prognostic factors cancer. Utilizing both univariate Cox regression lasso techniques, we identified ADME genes critical for patient outcomes. our study, model assessing risk was constructed. The evaluation of this model's predictive precision conducted using Kaplan–Meier survival curves assessments based on ROC curves. Furthermore, devised nomogram, offering straightforward visualization crucial indicators. To potential mediating differences between high low groups, performed comprehensive analyses including Gene Ontology (GO) Kyoto Encyclopedia Genomes (KEGG)-based enrichment analyses, immune infiltration variations, somatic mutation landscapes, pharmacological sensitivity response assessment etc. Immediately following this, selected core PPI network explored as well modulation, pathway activation. And differential expression verified by immunohistochemistry qRT-PCR. Finally pan-cancer biomarkers. Results efforts culminated establishment validated 17-gene ADME-centered prediction model, displaying remarkable accuracy BLCA prognosis. Through separate cox importance model’s score forecasting substantiated. novel nomogram incorporating variables alongside introduced. Comprehensive studies established strong correlation several key indicators: patterns cell infiltration, reactions immunotherapy, landscape profiles drug sensitivity. We screened gene CYP2C8, its tumor bioregulation upregulated found it can serve reliable biomarker pan-cancer. Conclusion formulated research stands formidable instrument prognosis, while also providing insights into disease's progression mechanisms guiding decision-making strategies.

Language: Английский

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Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 31, 2024

Abstract Cancer neuroscience is an emerging field that investigates the intricate relationship between nervous system and cancer, gaining increasing recognition for its importance. The central governs development of directly affects brain tumors, peripheral (PNS) shapes tumor microenvironment (TME) tumors. Both systems are crucial in cancer initiation progression, with recent studies revealing a more role PNS within TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating bidirectional interaction cancers. Notably, immune cells contribute this communication, forming triangular influences protumor inflammation effectiveness immunotherapy. This review delves into mechanisms connecting focusing on how various cell types influence nerve‒tumor interactions, emphasizing clinical relevance nerve‒immune dynamics. By deepening our understanding interplay nerves, cells, has potential reshape biology insights, inspire innovative therapies, improve outcomes patients.

Language: Английский

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Pan-Cancer Genetic Analysis of Mitochondrial DNA Repair Gene Set

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract Background The mitochondrial DNA repair has gained attention for its potential impact on pan-cancer genetic analysis. This study investigates the clinical relevance of genes: PARP1, 2, PRIMPOL, TP53, MGME1. Methods Using multi-omics profiling data and Gene Set Cancer Analysis (GSCA) with normalized SEM mRNA expression, this research analyzes differential gene mutation, drug correlation. Results TP53 was most commonly mutated mitochondrial-related in cancer, UCS OV having highest mutation rates. CPG mutations linked to lowest survival Breast various subtypes, potentially influenced by genes. ACC shown be high BRCA, USC, LUCS, COAD, showed CNV levels impacting survival. A negative expression-methylation correlation observed weakest KIRC. Mitochondrial genes were Cell cycle_A activation. weak found between immune infiltration Few compounds affected Conclusion Understanding could redefine cancer diagnosis, prognosis, serve as therapeutic biomarkers, altering cell behavior treatment outcomes.

Language: Английский

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Protein Kinases in Phagocytosis: Promising Genetic Biomarkers for Cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Cancer is a complex disease characterized by genetic and molecular diversity, often involving dysregulation of critical cellular pathways. Recent advances in pan-cancer research have highlighted the importance shared oncogenic mechanisms across different cancer types, providing new avenues for therapeutic exploration. Protein kinases, particularly those involved phagocytosis, play pivotal roles homeostasis immune response. This study systematically examines alterations expression profiles protein kinases associated with phagocytosis various using data from The Genome Atlas (TCGA) other publicly available resources. We analyzed single nucleotide variations (SNVs), copy number (CNVs), methylation patterns, mRNA to identify recurring their associations survival outcomes. Our findings reveal that MET MERTK are most frequently mutated genes, missense mutations dominating cancers. CNV analysis shows significant correlations cancers like UCEC, KIRP, KIRC, while indicates cancer-specific regulatory patterns affecting gene expression. Differential highlights distinct cancer-type-specific profiles, genes BTK displaying variation. Crosstalk pathway further reveals involvement these key cancer-related pathways, such as epithelial-mesenchymal transition (EMT) apoptosis. Drug sensitivity identifies potential targets, correlating significantly cell line responsiveness specific compounds. These underscore phagocytotic kinome biology suggest strategies targeting enhance response improve treatment

Language: Английский

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Identification of Lauric Acid as a Potent Sodium Channel NaV1.5 Blocker from Compound Chinese Medicine Wenxin Keli

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 141 - 157

Published: Jan. 1, 2025

Purpose: The major cardiac voltage-gated sodium channel Na V 1.5 (I ) is essential for action potential initiation and subsequent propagation. Compound Chinese medicine Wenxin Keli (WXKL) has been shown to suppress arrhythmias heart failure. However, its active components have not fully elucidated. This study focused on identifying the inhibitor of I in WXKL exploring their mode electrophysiological conduction. Methods: A chemical fraction library was constructed from an aqueous extract screened using automated patch-clamping system cells stably expressing gene SCN5A. Candidate fractions with -inhibition activity were analyzed by HPLC-ESI-IT-TOF-MS GC-MS identify ingredients. blocker molecules identified single-cell electrocardiogram tested hiPSC-derived cardiomyocytes. We evaluated SCN5A inhibitory effective monomer employing molecular docking dynamics simulation approaches. Results: primary screen five that significantly inhibited channel, one them rich poly-saturated fatty acids. Molecular structural characterization revealed presence lauric acid, myristic palmitic stearic acid subfraction. Electrophysiological demonstrated (LA) as most IC 50 at 27.40 ± 12.78 μM. LA shifted steady-state inactivation more negative potentials decreased amplitude extracellular field demonstrate first time naturally a novel blocker. suggested binds protein, significant binding affinity forming interactions functionally residues blocks inward flow + . Mechanistically, acts fast alter electrophysiology conduction cardiomyocytes contribute antiarrhythmic effect WXKL. Conclusion: Lauric potent alleviates arrhythmia via inhibiting Keywords: Keli, arrythmia, patch clamp recording, high-throughput

Language: Английский

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Identification of patients with advanced pancreatic cancer who might benefit from third-line chemotherapy

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(2)

Published: Jan. 18, 2025

Survival rates of patients with advanced pancreatic cancer (APC) have been improved palliative chemotherapy series. The current preferred first-line regimen consists combination therapy 5-fluorouracil (5-FU)/leucovorin (LV), irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus albumin-bound paclitaxel (GNP). After failure chemotherapy, there are a few options for subsequent including switch to the unused nano-liposomal irinotecan 5-FU/LV. However, limited studies on efficacy third-line after second-line chemotherapy. To identify APC who might benefit from Medical records single tertiary hospital were retrospectively reviewed between 2012 2021. study included histologically cytologically confirmed metastatic locally underwent FOLFIRINOX GNP subsequently received Overall survival (OS) diagnosis OS (OS3) defined as interval all-cause death time initiation death, respectively. A total 141 enrolled. median patient age at was 61.8 years (36.0-86.0), 54.9% male. (67.4%) (32.6%). (27.0%), (52.5%), other (20.6%). 19.0 months, OS3 progression-free treatment 15.3 7.3 weeks, With regard best tumor response during 1.4% had partial response, 24.8% stable disease, 59.6% progressive disease. following clinical factors before affected OS3: Good performance status (PS), serum carbohydrate antigen 19-9 (CA19-9) level < 1000 U/mL, duration ≥ 19 no peritoneal seeding. This identified that good PS, CA19-9 seeding starting may more

Language: Английский

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Uridine-cytidine kinase 2 is correlated with immune, DNA damage repair and promotion of cancer stemness in pan-cancer

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 27, 2025

Background UCK2 (Uridine-Cytidine Kinase 2) is a promising prognostic marker for malignant tumors, but its association with immune infiltration and cancer stemness in pan-cancer remains to be fully understood. we find that gene closed related RNA scores (RNAss) DNA (DNAss), which measured the tumor stemness. We also discover an between expression cells by CIBERSORT algorithm, ESTIMATE algorithm ssGSEA especially, T cell, monocytes, mast cells, macrophages. This study aims shed light on role possible mechanism of pan-cancer. Methods used R programming language bulk sequencing data analysis, were obtained from University California, Santa Cruz (UCSC) datasets. UCSC database very useful explore TCGA other genomics datasets, The explored at transcriptome level came database. differential normal samples. Immunohistochemistry (IHC) was utilized validate different types cancers using tissue chips. correlations prognosis, genetic instability, repair, stem cell characteristics, investigated. Furthermore, single-cell acquired Gene Expression Omnibus (GEO) database, relationship cells. GEO famous public supporting freely disseminates microarray data. Finally, analyzed correlation drug sensitivity. Results observed high most remarkably prognosis pan-cancers. found increased associated higher instability. Additionally, positive relationships mismatch repair genes, homologous recombination across types. There significant Moreover, as expected, checkpoint human leucocyte antigen (HLA) negatively UCK2. Similarly, have negative major histocompatibility complex (MHC) genes. noted had sensitivity various anti-cancer drug. Conclusion plays pivotal roles immunity, it exhibits strong checkpoints HLA. highlights potential impact

Language: Английский

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