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PeerJ 2023The sequencing panel composed of 61 target genes was used to explore the related mutation genes of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF)...
OBJECTIVE
The sequencing panel composed of 61 target genes was used to explore the related mutation genes of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF) cancerization, so as to provide a theoretical basis for the early diagnosis of oral submucous fibrosis cancerization, find the most important mutations in OSF cancerization, and more targeted prevention of OSF cancerization.
METHODS
A total of 74 clinically diagnosed samples were included, including 36 cases of OSCC and 38 cases of OSF cancer patients. DNA was extracted, and targeted gene panel sequencing technology was used to analyze the gene frequency of pathogenic mutation sites in clinical samples.
RESULTS
Gene panel sequencing analysis showed that there were 69 mutations in 18 genes in OSCC and OSF cancerous specimens. The results of gene panel sequencing were screened, and 18 mutant genes were finally screened out and their mutation frequencies in the samples were analyzed. According to the frequency of gene mutations from high to low, they were TP53, FLT4, PIK3CA, CDKN2A, FGFR4, HRAS, BRCA1, PTPN11, NF1, KMT2A, RB1, PTEN, MSH2, MLH1, KMT2D, FLCN, BRCA2, APC. The mutation frequency of FLT4 gene was significantly higher than that of OSCC group ( < 0.05).
CONCLUSION
FLT4 gene may be related to OSF cancerization and is expected to be an early diagnostic biomarker for OSF cancerization.
Topics: Humans; Oral Submucous Fibrosis; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation
PubMed: 38050610
DOI: 10.7717/peerj.16392 -
Journal of the American Heart... Feb 2020Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in...
Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in humans is lacking. We examined peripheral blood Wnt pathway gene expression and arterial stiffness in 369 healthy African ancestry men (mean age, 64 years). Methods and Results Gene expression was assessed using a custom Nanostring nCounter gene expression panel (N=43 genes) and normalized to housekeeping genes and background signal. Arterial stiffness was assessed via brachial-ankle pulse-wave velocity. Fourteen Wnt genes showed detectable expression and were tested individually as predictors of pulse-wave velocity using linear regression, adjusting for age, height, weight, blood pressure, medication use, resting heart rate, current smoking, alcohol intake, and sedentary lifestyle. Adenomatous polyposis coli regulator of Wnt signaling pathway (), glycogen synthase kinase 3β (), and transcription factor 4 () were significantly associated with arterial stiffness (<0.05 for all). When entered into a single model, and expression remained independently associated with arterial stiffness (=0.04 and 0.003, respectively), and each explained ≈3% of the variance in pulse-wave velocity. Conclusions The current study establishes a novel association between in vivo expression of the Wnt pathway genes, and , with arterial stiffness in African ancestry men, a population at high risk of hypertensive vascular disease.
Topics: Adenomatous Polyposis Coli Protein; Aged; Aged, 80 and over; Ankle Brachial Index; Black People; Gene Expression Profiling; Humans; Male; Middle Aged; Prospective Studies; Pulse Wave Analysis; Transcription Factor 4; Transcriptome; Trinidad and Tobago; Vascular Stiffness; Wnt Signaling Pathway
PubMed: 32013702
DOI: 10.1161/JAHA.119.014170 -
Frontiers in Genetics 2022The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and...
The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and is associated with clinical outcomes of patients with multiple tumors. Nonetheless, the significance of TMEM genes in the prognosis prediction of patients with osteosarcoma remains largely unclear. Here, we comprehensively analyzed TMEM protein family genes in osteosarcoma using public resources and bioinformatics methods. Prognosis-related TMEM protein family genes were identified by the univariate Cox regression analysis and were utilized to construct a signature based on six TMEM protein family genes (, , , , , and ) in osteosarcoma. The prognostic signature stratified patients into high- and low-risk groups, and validation in the internal and external cohorts confirmed the risk stratification ability of the signature. Functional enrichment analyses of differentially expressed genes between high- and low-risk groups connected immunity with the prognostic signature. Moreover, we found that M2 and M0 macrophages were the most abundant infiltrated immune cell types in the immune microenvironment, and samples of the high-risk group showed a decreased proportion of M2 macrophages. Single-sample gene set enrichment analysis revealed that the scores of neutrophils and Treg were markedly lower in the high-risk group than these in the low-risk group in The Cancer Genome Atlas and GSE16091 cohorts. As for the related immune functions, APC co-inhibition and cytolytic activity exhibited fewer active levels in the high-risk group than that in the low-risk group in both cohorts. Of the six TMEM genes, the expression of was lower in the high-risk group than in the low-risk group and was positively associated with the overall survival of osteosarcoma patients. In conclusion, our TMEM protein family gene-based signature is a novel and clinically useful prognostic biomarker for osteosarcoma patients, and might be a potential therapeutic target in osteosarcoma.
PubMed: 35991561
DOI: 10.3389/fgene.2022.937300 -
Asian Pacific Journal of Cancer... Dec 2021It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and...
OBJECTIVE
It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers.
METHODS
A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated.
RESULTS
The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05).
CONCLUSION
We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Colonic Neoplasms; DNA Glycosylases; Female; Genes, APC; Genes, p53; Genetic Predisposition to Disease; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Neoplasm Metastasis; Retrospective Studies; Survival Analysis; Young Adult
PubMed: 34967562
DOI: 10.31557/APJCP.2021.22.12.3839 -
Bioscience Reports Mar 2020To study the correlation between adenomatous polyposis coli (APC) gene 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) and their interactions with...
OBJECTIVE
To study the correlation between adenomatous polyposis coli (APC) gene 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) and their interactions with environmental factors and the risk of colorectal cancer (CRC) in a Chinese Han population.
METHODS
Genotypes of APC gene 3'UTR rs1804197, rs41116, rs448475, and rs397768 loci in 340 Chinese Han patients with CRC and 340 healthy controls were analyzed. All patients with CRC were analyzed for progression-free survival (PFS) during a 3-year follow-up.
RESULTS
The risk of CRC in subjects carrying the APC gene rs1804197 A allele was 2.95-times higher than for the C allele carriers. The interactions of the rs1804197 SNP with body mass index (BMI) and smoking were associated with the risk of CRC. The risk of CRC in the APC gene rs397768 G allele carriers was 1.68-times higher than in the A allele carriers. The interaction between the rs397768 locus SNP and gender was also associated with the risk of CRC. The 3-year PFS of patients with APC gene rs1804197 AA genotype, CA genotype, and CC genotype CRC decreased in this order, with significant difference. In addition, the 3-year PFS of rs397768 locus GG genotype, AG genotype, and AA genotype CRC patients decreased in this order, and the difference was significant.
CONCLUSION
The rs1804197 locus in the 3'UTR region of the APC gene and its interactions with BMI and smoking are associated with the risk of CRC in a Chinese Han population. In addition, the interaction between rs397768 locus SNP and gender is related to the risk of CRC.
Topics: 3' Untranslated Regions; Adenomatous Polyposis Coli; Adult; Aged; Alleles; Asian People; Case-Control Studies; China; Colorectal Neoplasms; Epistasis, Genetic; Ethnicity; Female; Gene Frequency; Gene-Environment Interaction; Genes, APC; Genetic Predisposition to Disease; Genotype; Heterozygote; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 32159210
DOI: 10.1042/BSR20192429 -
European Journal of Human Genetics :... Jan 2020Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic...
Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene. Index patients with suspected FAP are usually investigated by APC coding region sequence and dosage analysis in a clinical diagnostic setting. The identification of an APC variant which is predicted to alter protein function enables predictive genetic testing to guide the management of family members. This report describes a 4-generation family with a phenotype consistent with FAP, but in which an APC variant had not been identified, despite testing. To explore this further, quantitative PCR (qPCR) was employed to assess APC transcription, demonstrating reduced levels of APC RNA. Next generation sequencing (NGS) identified the APC 5'UTR/ Exon 1 variant, c.-190 G>A, that had been reported previously in an another FAP family with APC allelic imbalance. Quantitative RNA studies and DNA sequencing of the APC promoters/ Exon 1 may be useful diagnostically for patients with suspected FAP when coding region variants cannot be identified.
Topics: 5' Untranslated Regions; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Humans; Mutation; Pedigree; Promoter Regions, Genetic; RNA, Messenger
PubMed: 31383941
DOI: 10.1038/s41431-019-0486-2 -
Genes & Diseases Sep 2023This study aims to identify the inflammatory factor-related genes which help to predict the prognosis of patients with colorectal cancer. GSEA (Gene Set Enrichment...
This study aims to identify the inflammatory factor-related genes which help to predict the prognosis of patients with colorectal cancer. GSEA (Gene Set Enrichment Analysis) was used to acquire inflammation-related genes and the corresponding expression information was collected from TCGA database to determine the DEGs (differentially-expressed genes) in CRC patients. We conducted enrichment analysis and PPI (protein-protein interaction) of these DEGs. Besides, key genes that are both differentially-expressed and prognosis-related were screened out, which were used to establish the prognostic model. We obtained 79 DEGs and 19 prognostic genes, 10 prognostic-related differential genes were eventually screened. These genes were used to construct the prognostic model. We also identified that the immune infiltration score of macrophages between different risk groups was significantly different and similar distinction was witnessed in immune function score of APC (antigen-presenting cell) co-stimulation and type I IFN (interferon) response.
PubMed: 37492736
DOI: 10.1016/j.gendis.2022.07.015 -
Asian Pacific Journal of Cancer... Nov 2023The present study was aimed to investigate the APC expression, its promoter methylation status, the expression of β-Catenin, c-Myc and Cyclin D1 and further explore...
OBJECTIVE
The present study was aimed to investigate the APC expression, its promoter methylation status, the expression of β-Catenin, c-Myc and Cyclin D1 and further explore their prognostic value in Hepatocellular carcinoma (HCC).
PATIENTS AND METHODS
Serum samples from 90 HCC patients and 27 healthy donors were collected in this study. The methylation-specific PCR (MSP) was performed to evaluate promoter methylation status of APC gene. RT-qPCR was used to detect the mRNA expression of APC, β-Catenin, c-Myc and Cyclin D1, meanwhile the protein expression were analyzed by Western blot.
RESULTS
The positive rate of APC gene methylation in HCC patients (46.67%) was higher than healthy donors (11.11%). APC gene exhibited marked hypermethylation in the patients of TNM III-IV stage when compared to the patients of TNM I-II stage , the methylation status of APC gene was correlated with tumor size and lymph node metastasis whereas the APC gene methylation showed no relationship with the patient's sex and age. APC methylation may be associated with APC expression level, APC expression in HCC cells is silenced by aberrant promoter hypermethylation. In HCC patients with methylated APC, the mRNA and protein expression of β-Catenin, c-Myc and Cyclin D1 were higher than the unmethylated patient subgroup and healthy donors.
CONCLUTIONS
The downregulation of APC in HCC samples was associated with promoter hypermethylation. APC methylation could be used as a novel diagnostic biomarker in HCC, which was associated with regulation of Wnt/β-Catenin signal pathway.
Topics: Humans; beta Catenin; Carcinoma, Hepatocellular; Cyclin D1; Liver Neoplasms; Prognosis; RNA, Messenger; Promoter Regions, Genetic; DNA Methylation
PubMed: 38019243
DOI: 10.31557/APJCP.2023.24.11.3851 -
Cancers Mar 2021Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10-15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is... (Review)
Review
Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10-15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is frequently associated with resistance to apoptosis. Inferior prognosis is observed in mucinous CRC, particularly in rectal cancer and metastatic cases. Mucins are heavily glycosylated secretory or transmembrane proteins that participate in protection of the colonic epithelium. MUC2 overexpression is a hallmark of mucinous CRCs. Mucinous CRC is associated with KRAS and BRAF mutation, microsatellite instability and the CpG island methylator phenotype. Mutations of the gene and mutations which are characteristic non-mucinous colorectal adenocarcinoma are less common in mucinous CRC. Both physical and anti-apoptotic properties of mucin provide mechanisms for resistance to cell death. Mucin glycoproteins are associated with decreased expression of pro-apoptotic proteins, increased expression of anti-apoptotic proteins and increased cell survival signaling. The role for BCL-2 proteins, including BCL-X, in preventing apoptosis in mucinous CRC has been explored to a limited extent. Additional mechanisms opposing cell death include altered death receptor expression and altered mutation rates in genes responsible for chemotherapy resistance. The roles of alternate cell death programs including necroptosis and pyroptosis are not well understood in mucinous CRC. While the presence of MUC2 is associated with an immunosuppressive environment, the tumor immune environment of mucinous CRC and the role of immune-mediated tumor cell death likewise require further investigation. Improved understanding of cell death mechanisms in mucinous CRC may allow modification of currently used regimens and facilitate targeted treatment.
PubMed: 33808549
DOI: 10.3390/cancers13061389 -
Genes Aug 2021Mammalian circRNAs are covalently closed circular RNAs often generated through backsplicing of precursor linear RNAs. Although their functions are largely unknown, they...
Mammalian circRNAs are covalently closed circular RNAs often generated through backsplicing of precursor linear RNAs. Although their functions are largely unknown, they have been found to influence gene expression at different levels and in a wide range of biological processes. Here, we investigated if some circRNAs may be differentially abundant in Alzheimer's Disease (AD). We identified and analyzed publicly available RNA-sequencing data from the frontal lobe, temporal cortex, hippocampus, and plasma samples reported from persons with AD and persons who were cognitively normal, focusing on circRNAs shared across these datasets. We identified an overlap of significantly changed circRNAs among AD individuals in the various brain datasets, including circRNAs originating from genes strongly linked to AD pathology such as , , (implicated in synaptic plasticity and neuronal survival) and /, , and (implicated in vesicular traffic). We further predicted the presence of circRNA isoforms in AD using specialized statistical analysis packages to create approximations of entire circRNAs. We propose that the catalog of differentially abundant circRNAs can guide future investigation on the expression and splicing of the host transcripts, as well as the possible roles of these circRNAs in AD pathogenesis.
Topics: Adenomatous Polyposis Coli Protein; Alzheimer Disease; Brain; Female; Gene Expression Profiling; Gene Regulatory Networks; Genome, Human; Humans; Intercellular Signaling Peptides and Proteins; Kinesins; Male; Membrane Glycoproteins; MicroRNAs; Neuronal Plasticity; Neurons; RNA Splicing; RNA, Circular; Receptor, trkB; Sequence Analysis, RNA; rac GTP-Binding Proteins
PubMed: 34440432
DOI: 10.3390/genes12081258