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Publication
Journal: OncoTargets and Therapy
June/21/2016
Abstract
OBJECTIVE
There has been considerable interest in using whole-genome expression profiles for the classification of colorectal cancer (CRC). The selection of important features is a crucial step before training a classifier.
METHODS
In this study, we built a model that uses support vector machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300, and 500 genes most relevant to CRC using the minimum-redundancy-maximum-relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function [RBF], and sigmoid).
RESULTS
The best model, which used 30 genes and RBF kernel, outperformed other combinations; it had an accuracy of 84% for both ten fold and leave-one-out cross validations in discriminating the cancer samples from the normal samples. With this 30 genes set from mRMR, six classifiers were trained using random forest (RF), Bayes net (BN), multilayer perceptron (MLP), naïve Bayes (NB), reduced error pruning tree (REPT), and SVM. Two hybrids, mRMR + SVM and mRMR + BN, were the best models when tested on other datasets, and they achieved a prediction accuracy of 95.27% and 91.99%, respectively, compared to other mRMR hybrid models (mRMR + RF, mRMR + NB, mRMR + REPT, and mRMR + MLP). Ingenuity pathway analysis was used to analyze the functions of the 30 genes selected for this model and their potential association with CRC: CDH3, CEACAM7, CLDN1, IL8, IL6R, MMP1, MMP7, and TGFB1 were predicted to be CRC biomarkers.
CONCLUSIONS
This model could be used to further develop a diagnostic tool for predicting CRC based on gene expression data from patient samples.
Publication
Journal: Journal of Chromatography A
July/7/2008
Abstract
An optical absorption sensor for gas chromatography (GC) is presented. It consists of a quantum cascade laser along with a long piece of Hollow Waveguide for Infrared (HWIR) transmission inserted into the GC line. It measures the infrared absorption in each individual gas peak after separation by the GC column, and maintains the shapes of gas peaks after the HWIR sensor, making the gas samples further available for other sensors. By adding an inline combustion module before the HWIR sensor, the concentrations of many carbon containing compounds can be acquired by measuring CO2 absorption in their peaks. The HWIR sensor detects isotopologues of CO2 separately, and therefore can be used to measure carbon isotope ratios of heavy compounds. Application of the HWIR sensor to the detection of 13CO2 and CDH3 is described.
Publication
Journal: Journal of Gene Medicine
August/17/2019
Abstract
Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders.The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction.We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM.A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.
Publication
Journal: Current Eye Research
February/10/2014
Abstract
OBJECTIVE
To determine putative limbal epithelial stem cell marker expression in human limbal dermoids compared to stem cell niches in normal limbus and hair follicles of normal human dermis.
METHODS
Human limbal dermoids (n = 7), normal skin (n = 2) and normal limbal (n = 7) tissue were examined. Immunohistochemistry was performed on paraffin embedded specimens using automated and manual immunostaining with primary antibodies to CK15, CK14, Cadherin-P (CDH3), Wnt-3, Wnt-4, Wnt-5a, Dickkopf (DKK)-3, Sox-2, Sox-10, Sox-13, PEDF, NGFR p75 and β-catenin.
RESULTS
Positive immunostaining was found for CK15, CK14, CDH3, NGFR p75, PEDF, Sox-2, Sox-10 and Wnt 4 in the basal dermoid epithelium, limbus and hair follicles. Suprabasal epithelium was immunostained with PEDF, Sox-2 and Wnt-4 in these tissues. The sebaceous and sweat glands, vascular endothelium and nerves of the limbal dermoid immunostained with PEDF and Sox-2. Sebaceous and sweat glands stained for Sox-10. DKK-3 immunostaining occurred in the dermoids' suprabasal epithelium and vascular endothelium but not in the limbus or hair follicle.
CONCLUSIONS
Human limbal dermoids share a similar antigenic expression profile similar to the basal limbal epithelium and to the stem cell niche of hair follicles. This supports the notion that limbal dermoids could have properties in common with limbal and/or dermal epithelial stem cells.
Publication
Journal: Medical Science Monitor
April/10/2016
Abstract
BACKGROUND
Colorectal Cancer (CRC) is one of the most frequently diagnosed neoplasms and also one of the main death causes. Cell adhesion molecules are taking part in specific junctions, contributing to tissue integrality. Lower expression of the cadherins may be correlated with poorer differentiation of the CRC, and its more aggressive phenotype. The aim of the study is to designate the cadherin genes potentially useful for the diagnostics, prognostics, and the treatment of CRC.
METHODS
Specimens were collected from 28 persons (14 female and 14 male), who were operated for CRC. The molecular analysis was performed using oligonucleotide microarrays, mRNA used was collected from adenocarcinoma, and macroscopically healthy tissue. The results were validated using qRT-PCR technique.
RESULTS
Agglomerative hierarchical clustering of normalized mRNA levels has shown 4 groups with statistically different gene expression. The control group was divided into 2 groups, the one was appropriate control (C1), the second (C2) had the genetic properties of the CRC, without pathological changes histologically and macroscopically. The other 2 groups were: LSC (Low stage cancer) and HSC (High stage cancer). Consolidated results of the fluorescency of all of the differential genes, designated two coding E-cadherin (CDH1) with the lower expression, and P-cadherin (CDH3) with higher expression in CRC tissue.
CONCLUSIONS
The levels of genes expression are different for several groups of cadherins, and are related with the stage of CRC, therefore could be potentially the useful marker of the stage of the disease, also applicable in treatment and diagnostics of CRC.
Publication
Journal: Frontiers in Psychology
December/6/2018
Abstract
Objective: To explore the targets, signal regulatory networks and mechanisms involved in Baixiangdan (BXD) capsule regulation of premenstrual dysphoric disorder (PMDD) at the gene transcription level, since the etiology and pathogenesis of PMDD are not well understood. Methods: The PMDD rat model was prepared using the resident-intruder paradigm. The rats were tested for aggressive behavior, and those with scores in the lowest 30% were used as controls, while rats with scores in the highest 30% were divided into a PMDD model group, BXD administration group and fluoxetine administration group, which were evaluated with open-field tests and aggressive behavior tests. We also analyzed gene expression profiles in the hippocampus for each group, and verified differential expression of genes by real-time PCR. Results: Before and after BXD or fluoxetine administration, scores in the open-field test exhibited no significant differences. The aggressive behavior of the PMDD model rats was improved to a degree after administration of both substances. Gene chip data indicated that 715 genes were differentially expressed in the control and BXD groups. Other group-to-group comparisons exhibited smaller numbers of differentially expressed genes. The effective targets of both drugs included the Htr2c, Cdh3, Serpinb1a, Ace, Trpv4, Cacna1a, Mapk13, Mapk8, Cyp2c13, and Htr1a genes. The results of real-time PCR tests were in accordance with the gene chip data. Based on the target genes and signaling pathway network analysis, we have elaborated the impact and likely mechanism of BXD in treating PMDD and premenstrual irritability. Conclusion: Our work contributes to the understanding of PMDD pathogenesis and the mechanisms of BXD treatment. We speculate that the differentially expressed genes could participate in neuroactive ligand-receptor interactions, mitogen-activated protein kinase, calcium, and gamma-aminobutyric acid signal transduction.
Publication
Journal: BMJ Case Reports
October/24/2019
Abstract
Here, we report the diagnostic challenge of a female patient of Russian descent with autosomal recessive hypotrichosis with juvenile macular dystrophy (HJMD). She presented to dermatology age one and a half years with sparse hair growth on her scalp, her parents were reassured this would grow, but it never manifested. She was found to be hypermetropic and prescribed glasses from age 2 but no retinal findings were noted. At age 23 years, the patient undertook an internet search and discovered the association of symptoms pointing towards HJMD. She sought genetic testing, revealing a homozygous missense mutation in Cadherin-3 (CDH3) gene. The patient presented to our Genetic Eye Disease Service at Moorfields Eye Hospital age 27 years, with reduced colour, central distance and near vision. Fundus examination and imaging confirmed atrophic macular changes. Currently, HJMD has no treatment, she wears a wig, UV-protected sunglasses in sunlight and maintains a healthy balanced diet.
Publication
Journal: American Journal of Ophthalmology Case Reports
August/21/2019
Abstract
We describe a unique case of CDH3-related hypotrichosis with juvenile macular dystrophy (HJMD) and DNAH5-related primary ciliary dyskinesia (PCD) with progressive vision loss in a young Indian female without positive family history. Both mutations in this patient have not been previously described in the literature.An 11-year-old girl of Indian descent from a consanguineous family presented to our clinic with poor central visual acuity, recurrent sinopulmonary infections, hypotrichosis, and gradual hearing loss. Fundus examination was significant for atrophic retinal pigmented epithelial (RPE) changes involving both the macula and periphery of both eyes with central foveal hypoautofluorescence. Optical coherence tomography (OCT) demonstrated RPE loss and significant disruption of the ellipsoid layer in both eyes. Full-field electrophysiology tests on initial presentation demonstrated low cone amplitude reduced to <70% of normal range without prolongation. OCT angiography of the RPE and choriocapillaris demonstrated possible flow voids in the central macular region of both eyes. Genetic testing showed that the proband was homozygous for variants CDH3 c.1660A > C; p. Thr554Pro and DNAH5 c.6688-1G>T.

Conclusion
and Importance: We report two novel variants in the CDH3 and DNAH5 genes that are important for future mutational analysis of both HJMD and PCD respectively. A relationship between the cadherin protein dysfunction in CDH3 mutations and the ciliopathy of DNAH5 mutations has not been established. HJMD is known to cause a longitudinal deterioration of cone and rod mediated function, therefore recognizing the symptoms, visual impairment, physical examination, and photographic and electrophysiological findings is crucial in counseling the patient, the family, and fellow clinicians.

Publication
Journal: Documenta Ophthalmologica
February/2/2019
Abstract
To investigate a very rare case of hypotrichosis with cone-rod dystrophy caused by a P-cadherin CDH3 mutation.A 16-year-old Syrian girl was examined at age 9 and 14 years with an ophthalmological examination, fundus imaging, OCT and electrophysiological recordings (ERG and PERG). A disease-targeted gene panel sequencing was performed.Fundus images showed pigmentations at the posterior eye pole to the mid periphery, as well as vessel tortuosity. OCT images revealed a loss of the outer retinal segments and IS/OS in the central macula. The scotopic and photopic ERGs showed moderately reduced amplitudes at age 9 years that became severely reduced at age of 14 years. The PERG was undetectable at age 9 years. In color vision testing, protan-deutan confusion errors occurred. Gene panel analysis revealed one homozygous mutation in CDH3 (c.1508G>A; p.Arg503His).This case shows that a CDH3 mutation besides macula dystrophy can cause widespread cone-rod dystrophy with hypotrichosis without any other pathology besides hypoplastic nails. This points to a common pathway of hair growth and photoreceptor development that can be disturbed by a CDH3 mutation (c.1508G>A; p.Arg503His) located in the EC4 repeat region of the gene.
Publication
Journal: Skin Appendage Disorders
February/21/2021
Abstract
Hypotrichosis with juvenile macular dystrophy is an autosomal recessive disorder due to a mutation in the CDH3 gene. As its name indicates, the disease classically presented with hypotrichosis and early visual impairment. We describe herein a family member with alopecia since birth associated with severe visual impairment in their early life. We suspect the diagnosis of hypotrichosis with juvenile macular dystrophy. Genetic testing confirms the clinical suspension. We emphasize the importance of genetic testing for proper genetic counseling.
Keywords: Blindness; Childhood alopecia; Genetic hair disorders; Hypotrichosis; Visual impairment.
Publication
Journal: IDrugs : the investigational drugs journal
August/25/2010
Abstract
The 101st Annual Meeting of the American Association for Cancer Research, held in Washington DC, included topics covering new therapeutic developments in the field of cancer research. This conference report highlights selected presentations on the development of the third-generation camptothecin analog TH-1320 (Threshold Pharmaceuticals Inc), the silencing of the androgen receptor in prostate cancer by the novel locked nucleic acid-based antisense oligonucleotide EZN-4176 (Enzon Pharmaceuticals Inc/Santaris Pharma A/S), the inhibition of PC-3 cell invasiveness and metastasis by the CXCR4 antagonist CTCE-9908 (British Canadian BioSciences Corp), the antitumor efficacy of the CDH3 mAb PPMX-2017 (Perseus Proteomics Inc), and an anti-IL-6 mAb (MedImmune LLC) that suppresses tumor growth in vivo.
Publication
Journal: Biochimica et Biophysica Acta - General Subjects
July/17/2017
Abstract
The repressive Nucleosome Remodeling and histone Deacetylation (NuRD) complex remodels the chromatin structure by coupling ATP-dependent remodeling activity with histone deacetylase function and plays important roles in regulating gene transcription, DNA damage repair and chromatin assembly. The complex is composed of six subunits: Metastasis Associated proteins MTA1/2/3 initially recruit histone chaperones RBBP4/7 followed by the histone deacetylases HDAC1/2 forming a core complex. Further association of the CpG-binding protein MBD2/3, p66α/β and the ATP-dependent helicase CDH3/4 constitutes the NuRD complex. Recent structural studies on truncated human proteins or orthologous have revealed that the stoichiometry of the MTA1-RBBP4 complex is 2:4. This study reports expression and purification of the intact human MTA2-RBBP7 complex using HEK293F cells as expression system. In analogy with findings on the Drosophila NuRD complex, we find that also the human MTA-RBBP can be isolated in vitro. Taken together with previous findings this suggests, that MTA-RBBP is a stable complex, with a central role in the initial assembly of the human NuRD complex. Refined 3D volumes of the complex generated from negative stain electron microscopy (EM) data reveals an elongated architecture that is capable of hinge like motion around the center of the particle.
Publication
Journal: Journal of Theoretical Biology
September/8/2018
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Most lung cancer is non-small cell lung cancer (NSCLC), in which malignant cells form in the lung epithelium. Mutations in multiple genes and environmental factors both contribute to NSCLC, and although some NSCLC susceptibility genes have been characterized, the pathogenesis of this disease remains unclear. To identify genes conferring NSCLC risk and determine their associated pathological mechanism, we combined genome-wide haplotype associated analysis with gene prioritization using 224,677 SNPs in 37 NSCLC cell lines and 116 unrelated European individuals. Five candidate genes were identified: ESR1, TGFBR1, INSR, CDH3, and MAP3K5. All of these have previously been implicated in NSCLC, with the exception of CDH3, which can therefore be considered a novel indicator of NSCLC risk. Functional annotation confirmed the relationship between these five genes and NSCLC. Our findings are indicative of the underlying pathological mechanisms of NSCLC and provide information to support future directions in diagnosing and treating NSCLC.
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Publication
Journal: Experimental and Therapeutic Medicine
July/8/2019
Abstract
Colon adenocarcinoma (COAD) is one of the most common types of malignancy of the digestive system, and a better understanding of the molecular mechanisms will contribute to an improvement in the quality of life for COAD patients. Cadherin 3 (CDH3), a gene encoding P-cadherin, is a major component of adherens junctions and is closely associated with the occurrence and development of a variety of tumor types. However, the current knowledge regarding the role of CDH3 in COAD is limited. The present study aimed to identify the relative mRNA and protein expression levels of CDH3 in COAD tissues, and whether CDH3 had any influence on the survival rate of patients with COAD. Analysis of differentially expressed genes using the UALCAN database revealed that CDH3 was significantly upregulated in COAD tissues, and reverse transcription-quantitative PCR analysis further confirmed that CDH3 was upregulated in 48 COAD tissues compared with that in their paired normal tissues (n=48). Consistent with this, analysis of the Human Protein Atlas database indicated that the expression levels of the CDH3 protein were upregulated in COAD tissues (n=11) compared with those in normal tissues (n=3; P=0.0245). Next, the association between the mRNA levels of CDH3 and the survival rate of the COAD patients was analyzed using the UALCAN database, and the Kaplan-Meier curves revealed that the CDH3 high expression group (n=69) had a better overall survival compared with that of the CDH3 medium/low expression group (n=210; P=0.037). Furthermore, analysis of clinical data of a cohort from our hospital indicated that the median survival time for COAD patients with high (n=20) and low (n=20) CDH3 levels was 55.5 and 43.5 months, respectively, and there was a significant difference in the survival time between the two groups (P=0.0078). The above results verified that CDH3 was significantly upregulated in the COAD tissues and that high expression of CDH3 predicts a good prognosis for COAD patients.
Publication
Journal: American Journal of Ophthalmology
August/15/2020
Abstract
Purpose: To determine the genetic background of sector retinitis pigmentosa (RP), natural history, in order to better inform patient counselling.
Design: Retrospective case series.
Methods: Review of clinical notes, retinal imaging including color fundus photography (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT), electrophysiological assessment (ERG), and molecular genetic testing was performed in patients with sector RP from a single tertiary referral center.
Main outcome: Measures: Reporting demographic data, signs and symptoms, visual acuity, molecular genetics, ERG, FAF and OCT findings.
Results: Twenty-six molecularly confirmed patients from 23 different families were identified, harboring likely disease-causing variants in nine genes. The mode of inheritance was autosomal recessive (AR, n=6: USH1C, n=2; MYO7A, n=2; CDH3, n=1; EYS, n=1), X-linked (XL, n=4: PRPS1, n=1; RPGR, n=3), and autosomal dominant (AD, n=16: IMPDH1, n=3; RP1, n=3; RHO, n=10), with a mean age of disease onset of 38.5, 30.5 and 39.0 years respectively. Five of these genes have not previously been reported to cause sector RP (PRPS1, MYO7A, EYS, IMPDH1, and RP1). Inferior and nasal predilection was common across the different genotypes and patients tended to maintain good central vision. Progression on serial FAF was observed in RPGR, MYO7A, CDH23, EYS, IMPDH1, RP1 and RHO-associated sector RP.
Conclusions: The genotypic spectrum of the disease is broader than previously reported. The provided longitudinal data will help to provide more accurate patient prognosis and counselling, as well as inform patients' potential participation in the increasing numbers of trials of novel therapeutics and access to future treatments.
Keywords: FAF; OCT; RP; dystrophy; fundus autofluorescence; genetics; inherited retinal disease; optical coherence tomography; retina; retinitis pigmentosa; sector; sectoral; sectorial.
Publication
Journal: Investigational New Drugs
January/26/2021
Abstract
Melanoma is a highly aggressive malignant skin tumor with a high rate of metastasis and mortality. In this study, a comprehensive bioinformatics analysis was used to clarify the hub genes and potential drugs. Download the GSE3189, GSE22301, and GSE35388 microarray datasets from the Gene Expression Omnibus (GEO), which contains a total of 33 normal samples and 67 melanoma samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) approach analyze DEGs based on the DAVID. Use STRING to construct protein-protein interaction network, and use MCODE and cytoHubba plug-ins in Cytoscape to perform module analysis and identified hub genes. Use Gene Expression Profile Interactive Analysis (GEPIA) to assess the prognosis of genes in tumors. Finally, use the Drug-Gene Interaction Database (DGIdb) to screen targeted drugs related to hub genes. A total of 140 overlapping DEGs were identified from the three microarray datasets, including 59 up-regulated DEGs and 81 down-regulated DEGs. GO enrichment analysis showed that these DEGs are mainly involved in the biological process such as positive regulation of gene expression, positive regulation of cell proliferation, positive regulation of MAP kinase activity, cell migration, and negative regulation of the apoptotic process. The cellular components are concentrated in the membrane, dendritic spine, the perinuclear region of cytoplasm, extracellular exosome, and membrane raft. Molecular functions include protein homodimerization activity, calmodulin-binding, transcription factor binding, protein binding, and cytoskeletal protein binding. KEGG pathway analysis shows that these DEGs are mainly related to protein digestion and absorption, PPAR signaling pathway, signaling pathways regulating stem cells' pluripotency, and Retinol metabolism. The 23 most closely related DEGs were identified from the PPI network and combined with the GEPIA prognostic analysis, CDH3, ESRP1, FGF2, GBP2, KCNN4, KIT, SEMA4D, and ZEB1 were selected as hub genes, which are considered to be associated with poor prognosis of melanoma closely related. Besides, ten related drugs that may have therapeutic effects on melanoma were also screened. These newly discovered genes and drugs provide new ideas for further research on melanoma.
Keywords: Bioinformatics analysis; Biomarkers; Drugs; Melanoma; Prognostic.
Publication
Journal: PLoS ONE
July/31/2020
Abstract
Vocal folds are a viscoelastic multilayered structure responsible for voice production. Vocal fold epithelial damage may weaken the protection of deeper layers of lamina propria and thyroarytenoid muscle and impair voice production. Systemic dehydration can adversely affect vocal function by creating suboptimal biomechanical conditions for vocal fold vibration. However, the molecular pathobiology of systemically dehydrated vocal folds is poorly understood. We used an in vivo rabbit model to investigate the complete gene expression profile of systemically dehydrated vocal folds. The RNA-Seq based transcriptome revealed 203 differentially expressed (DE) vocal fold genes due to systemic dehydration. Interestingly, function enrichment analysis showed downregulation of genes involved in cell adhesion, cell junction, inflammation, and upregulation of genes involved in cell proliferation. RT-qPCR validation was performed for a subset of DE genes and confirmed the downregulation of DSG1, CDH3, NECTIN1, SDC1, S100A9, SPINK5, ECM1, IL1A, and IL36A genes. In addition, the upregulation of the transcription factor NR4A3 gene involved in epithelial cell proliferation was validated. Taken together, these results suggest an alteration of the vocal fold epithelial barrier independent of inflammation, which could indicate a disruption and remodeling of the epithelial barrier integrity. This transcriptome provides a first global picture of the molecular changes in vocal fold tissue in response to systemic dehydration. The alterations observed at the transcriptional level help to understand the pathobiology of dehydration in voice function and highlight the benefits of hydration in voice therapy.
Publication
Journal: Frontiers in Genetics
May/2/2021
Abstract
Oral squamous cell carcinoma (OSCC) has a high mortality rate (∼50%), and the 5-year overall survival rate is not optimal. Cyto- and histopathological examination of cancer tissues is the main strategy for diagnosis and treatment. In the present study, we aimed to uncover immunohistochemical (IHC) markers for prognosis in Asian OSCC. From the collected 742 synthetic lethal gene pairs (of various cancer types), we first filtered genes relevant to OSCC, performed 29 IHC stains at different cellular portions and combined these IHC stains into 398 distinct pairs. Next, we identified novel IHC prognostic markers in OSCC among Taiwanese population, from the single and paired IHC staining by univariate Cox regression analysis. Increased nuclear expression of RB1 [RB1(N)↑], CDH3(C)↑-STK17A(N)↑ and FLNA(C)↑-KRAS(C)↑were associated with survival, but not independent of tumor stage, where C and N denote cytoplasm and nucleus, respectively. Furthermore, multivariate Cox regression analyses revealed that CSNK1E(C)↓-SHC1(N)↓ (P = 5.9 × 10-5; recommended for clinical use), BRCA1(N)↓-SHC1(N)↓ (P = 0.030), CSNK1E(C)↓-RB1(N)↑ (P = 0.045), [CSNK1E(C)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.000, rounded to three decimal places) and [BRCA1(N)-SHC1(N), FLNA(C)-KRAS(C)] (P = 0.020) were significant factors of poor prognosis, independent of lymph node metastasis, stage and alcohol consumption. An external dataset from The Cancer Genome Atlas HNSCC cohort confirmed that CDH3↑-STK17A↑ was a significant predictor of poor survival. Our approach identified prognostic markers with components involved in different pathways and revealed IHC marker pairs while neither single IHC was a marker, thus it improved the current state-of-the-art for identification of IHC markers.
Keywords: biomarker; cox regression; gene expression data; immunohistochemistry; oral cancer; overall survival; prognosis.
Publication
Journal: Molecular and Cellular Proteomics
November/13/2018
Abstract
Maternal-effect genes are especially critical for early embryonic development after fertilization and until massive activation of the embryonic genome occurs. By applying a tandem mass tag (TMT)-labeled quantitative proteomics combined with RNA sequencing approach, the proteome of the buffalo was quantitatively analyzed during parthenogenesis of mature oocytes and the two-cell stage embryo. Of 1908 quantified proteins, 123 differed significantly. The transcriptome was analyzed eight stages (GV, MII, 2-cell, 4-cell, 8-cell, 16-cell, morula, blastocyst) of Buffalo using the RNA sequencing approach, and a total of 3567 unique genes were identified to be differently expressed between all consecutive stages of pre-implantation development. Validation of proteomics results (TUBB3, CTNNA1, CDH3, MAP2K1), which are involved in tight junction and gap junction, revealing that the maternal expression of the proteins possibly plays a role in the formation of cellular junctions firstly after parthenogenetic activation. Correlation and hierarchical analyses of transcriptional profiles and the expression of NPM2 and NLRP5 mRNA of buffalo in vitro developed oocytes and parthenogenetic embryos indicated that the "maternal-to-zygotic transition" (MZT) process might exist in the model of parthenogenesis, which is similar to a normally fertilized embryo, and may occur between the 8-cell to 16-cell stage. These data provide a rich resource for further studies on maternal proteins and genes and are conducive to improving nuclear transfer technology.
Publication
Journal: Journal of Cellular and Molecular Medicine
May/19/2021
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with increasing incidence. It has been suggested that DNA methylation drives cancer development. However, the molecular mechanisms underlying iCCA progression and the roles of DNA methylation still remain elusive. In this study, weighted correlation networks were constructed to identify gene modules and hub genes associated with the tumour stage. We identified 12 gene modules, two of which were significantly positively or negatively related to the tumour stage, respectively. Key hub genes SLC2A1, CDH3 and EFHD2 showed increased expression across the tumour stage and were correlated with poor survival, whereas decrease of FAM171A1, ONECUT1 and PHYHIPL was correlated with better survival. Pathway analysis revealed hedgehog pathway was activated in CDH3 up-regulated tumours, and chromosome separation was elevated in tumours expressing high EFHD2. JAK-STAT pathway was overrepresented in ONECUT1 down-regulated tumours, whereas Rho GTPases-formins signalling was activated in PHYHIPL down-regulated tumours. Finally, significant negative associations between expression of EFHD2, PHYHIPL and promoter DNA methylation were detected, and alterations of DNA methylation were correlated with tumour survival. In summary, we identified key genes and pathways that may participate in progression of iCCA and proposed putative roles of DNA methylation in iCCA.
Keywords: DNA methylation; WGCNA; epigenetics; intrahepatic cholangiocarcinoma; progression; transcriptome.
Publication
Journal: Faraday Discussions
October/18/2000
Abstract
High resolution pulsed-field-ionization (PFI) zero-kinetic-energy (ZEKE) photoelectron spectroscopy has been used to record the photoelectron spectra of CH4, CDH3, CD2H2 and CD4. The observed extensive progression of rotationally resolved transitions between 100,800 cm-1 and 104,100 cm-1 reveals for the first time the complex energy level structure of the methane cation. The high resolution enabled the determination of accurate values for the adiabatic ionization potentials of the different isotopomers. Based on a simple one-dimensional model for the pseudorotation in the different isotopomers, progress has been made towards the understanding of the Jahn-Teller effect at low energies. The static Jahn-Teller distortion in the ion could be determined directly from the vibrationless photoelectron transition in CD2H2. The analysis of the rotational structure in this spectrum with a rigid rotor model leads to an approximate experimental C2v structure. The dynamics of the other methane isotopomers near the adiabatic ionization potentials is dominated by large amplitude vibrational motions between equivalent structures. The corresponding ground state tunneling motions takes place on a picosecond time scale.
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Publication
Journal: Clinical Genetics
November/7/2019
Publication
Journal: ACS Synthetic Biology
May/20/2021
Abstract
Multicellular systems possess an intrinsic capacity to autonomously generate nonrandom state distributions or morphologies in a process termed self-organization. Facets of self-organization, such as pattern formation, pattern elaboration, and symmetry breaking, are frequently observed in developing embryos. Artificial stem cell-derived structures including embryoid bodies (EBs), gastruloids, and organoids also demonstrate self-organization, but with a limited capacity compared to their in vivo developmental counterparts. There is a pressing need for better tools to allow user-defined control over self-organization in these stem cell-derived structures. Here, we employ synthetic biology to establish an efficient platform for the generation of self-organizing coaggregates, in which HEK-293 cells overexpressing P-cadherin (Cdh3) spontaneously form cell clusters attached mostly to one or two locations on the exterior of EBs. These Cdh3-expressing HEK cells, when further engineered to produce functional mouse WNT3A, evoke polarized and gradual Wnt/β-catenin pathway activation in EBs during coaggregation cultures. The localized WNT3A provision induces nascent mesoderm specification within regions of the EB close to the Cdh3-Wnt3a-expressing HEK source, resulting in pattern elaboration and symmetry breaking within EBs. This synthetic biology-based approach puts us closer toward engineering synthetic organizers to improve the realism in stem cell-derived structures.
Keywords: Wnt3a; embryoid body; patterning; self-organization; symmetry breaking; synthetic biology.
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Publication
Journal: Oncology Letters
May/9/2021
Abstract
Numerous studies have reported that abnormal cadherin 3 (CDH3) and microRNA (miRNA/miR)-665 expression can induce the progression of gastric cancer (GC). However, the mechanism of interaction between miR-665 and CDH3 in GC requires further investigation. The present study aimed to investigate the influence of miR-665 and CDH3 in GC development. The effect of miR-665 and CDH3 on GC tissues and cell lines was examined using reverse transcription-quantitative PCR. Subsequently, CDH3 protein expression in GC cell lines was detected using western blotting. To confirm the association between miR-665 and CDH3, a dual-luciferase reporter assay system was employed. Cell proliferation and adhesion were analyzed using BrdU ELISA, MTT and cell adhesion assays. Finally, caspase-3 activity assay kit and FITC apoptosis detection kit were used for the determination of apoptosis of GC cells. The current findings confirmed the upregulation of CDH3 expression in GC cell lines and tissues. Experimental results indicated that CDH3 overexpression increased cell proliferation and adhesion, but decreased the apoptosis level of the cells. Similarly, the miR-665 inhibitor enhanced cell proliferation and adhesion, but inhibited apoptosis of GC cells. Additionally, it was observed that CDH3 was a direct target of miR-665 in GC cells and that miR-665 inhibited CDH3 expression, thereby repressing the progression of GC. In conclusion, the present study suggested that by targeting CDH3, miR-665 suppressed the progression of GC. These findings may provide a significant theoretical basis for future GC clinical therapy.
Keywords: adhesion; apoptosis; cadherin 3; gastric cancer; microRNA-665; proliferation.
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