UBE2T Contributes to the Prognosis of Esophageal Squamous Cell Carcinoma

Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC).Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA–ESCC cohort.Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and high-risk groups with significantly different overall survival in the TCGA–ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group.Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.

Download Full-text

Identification of Biomarkers of Hepatocellular Carcinoma Gene Prognosis Based on Immune-Related lncRNA Signature of Transcriptome Data

10.21203/rs.3.rs-57303/v1 ◽

2020 ◽

Author(s):

Andi Ma ◽

Yukai Sun ◽

Racheal O. Ogbodu ◽

Ling Xiao ◽

Haibing Deng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

Risk Group ◽

Enrichment Analysis ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Pathway Enrichment Analysis ◽

Cox Regression Analysis

Abstract Background: It is well known that long non-coding RNAs (lncRNAs) play a vital role in cancer. We aimed to explore the prognostic value of potential immune-related lncRNAs in hepatocellular carcinoma (HCC). Methods: Validated the established lncRNA signature of 343 patients with HCC from The Cancer Genome Atlas (TCGA) and 81 samples from Gene Expression Omnibus (GEO). Immune-related lncRNAs for HCC prognosis were evaluated using Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. LASSO analysis was performed to calculate a risk score formula to explore the difference in overall survival between high- and low-risk groups in TCGA, which was verified using GEO, Gene Ontology (GO), and pathway-enrichment analysis. These analyses were used to identify the function of screened genes and construct a co-expression network of these genes. Results: Using computational difference algorithms and lasso Cox regression analysis, the differentially expressed and survival-related immune-related genes (IRGs) among patients with HCC were established as five novel immune-related lncRNA signatures (AC099850.3, AL031985.3, PRRT3-AS1, AC023157.3, MSC-AS1). Patients in the low‐risk group showed significantly better survival than patients in the high‐risk group ( P = 3.033e−05). The signature identified can be an effective prognostic factor to predict patient survival. The nomogram showed some clinical net benefits predicted by overall survival. In order to explore its underlying mechanism, several methods of enrichment were elucidated using Gene Set Enrichment Analysis. Conclusion: Identifying five immune-related lncRNA signatures has important clinical implications for predicting patient outcome and guiding tailored therapy for patients with HCC with further prospective validation.

Download Full-text

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190717124507 ◽

2019 ◽

Vol 22 (6) ◽

pp. 411-420 ◽

Cited By ~ 5

Author(s):

Xian-Jun Wu ◽

Xin-Bin Zhou ◽

Chen Chen ◽

Wei Mao

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Signaling Pathway ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Pathway Enrichment ◽

Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Download Full-text

A Hypoxia-related LncRNA Signature Predicts Survival of Primary Lower-grade glioma

10.21203/rs.3.rs-335140/v1 ◽

2021 ◽

Author(s):

Yanjia Hu ◽

Jing Zhang ◽

Jing Chen

Keyword(s):

High Risk ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Enrichment Analysis ◽

High Risk Group ◽

Gene Set Enrichment Analysis ◽

Lower Grade ◽

Prognostic Signature ◽

Gene Set Enrichment

Abstract Background Hypoxia-related long non-coding RNAs (lncRNAs) have been proven to play a role in multiple cancers and can serve as prognostic markers. Lower-grade gliomas (LGGs) are characterized by large heterogeneity. Methods This study aimed to construct a hypoxia-related lncRNA signature for predicting the prognosis of LGG patients. Transcriptome and clinical data of LGG patients were obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). LGG cohort in TCGA was chosen as training set and LGG cohorts in CGGA served as validation sets. A prognostic signature consisting of fourteen hypoxia-related lncRNAs was constructed using univariate and LASSO Cox regression. A risk score formula involving the fourteen lncRNAs was developed to calculate the risk score and patients were classified into high- and low-risk groups based on cutoff. Kaplan-Meier survival analysis was used to compare the survival between two groups. Cox regression analysis was used to determine whether risk score was an independent prognostic factor. A nomogram was then constructed based on independent prognostic factors and assessed by C-index and calibration plot. Gene set enrichment analysis and immune cell infiltration analysis were performed to uncover further mechanisms of this lncRNA signature. Results LGG patients with high risk had poorer prognosis than those with low risk in both training and validation sets. Recipient operating characteristic curves showed good performance of the prognostic signature. Univariate and multivariate Cox regression confirmed that the established lncRNA signature was an independent prognostic factor. C-index and calibration plots showed good predictive performance of nomogram. Gene set enrichment analysis showed that genes in the high-risk group were enriched in apoptosis, cell adhesion, pathways in cancer, hypoxia etc. Immune cells were higher in high-risk group. Conclusion The present study showed the value of the 14-lncRNA signature in predicting survival of LGGs and these 14 lncRNAs could be further investigated to reveal more mechanisms involved in gliomas.

Download Full-text

Gene Expression Profile of Active HE4 Stimulation in Epithelial Ovarian Cancer Cells: Microarray Study and Comprehensive Bioinformatics Analysis

10.21203/rs.3.rs-46014/v1 ◽

2020 ◽

Author(s):

Liancheng Zhu ◽

Mingzi Tan ◽

Haoya Xu ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Clinical Significance ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Coexpression Analysis ◽

Pathway Enrichment

Abstract Background.Human Epididymis Protein 4 (HE4) is a novel serum biomarker for diagnosis of epithelial ovarian cancer (EOC) with high specificity and sensitivity compared with CA125, and the increasing researches have been carried out on its roles in promoting carcinogenesis and chemoresistance in EOC in recent years, however, its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of HE4 stimulation and to identify the key genes and pathways mediating carcinogenesis in EOC using microarray and bioinformatics analysis.Methods. We established a stable HE4-silence ES-2 ovarian cancer cell line labeled as “S”, and its active HE4 protein stimulated cells labeled as “S4”. Human whole genome microarray analysis was used to identify deferentially expressed genes (DEGs) from triplicate samples of S4 and S cells. “clusterProfiler” package in R, DAVID, Metascape, and Gene Set Enrichment Analysis (GSEA) were used to perform gene ontology (GO) and pathway enrichment analysis, and cBioPortal for WFDC2 coexpression analysis. GEO dataset (GSE51088) and quantitative real-time polymerase chain reaction (qRT-PCR) was applied for validation. The protein–protein interaction (PPI) network and modular analyses were performed using Metascape and Cytoscape. Results.In total, 713 DEGs were found (164 up regulated and 549 down regulated) and further analyzed by GO, pathway enrichment and PPI analyses. We found that MAPK pathway accounted for a significant portion of the enriched terms. WFDC2 coexpression analysis revealed ten WFDC2 coexpressed genes (TMEM220A, SEC23A, FRMD6, PMP22, APBB2, DNAJB4, ERLIN1, ZEB1, RAB6B, and PLEKHF1) that were also dramatically changed in S4 cells and validated by dataset GSE51088. Kaplan–Meier survival statistics revealed clinical significance for all of the 10 target genes. Finally, PPI was constructed, sixteen hub genes and eight molecular complex detections (MCODEs) were identified, the seeds of five most significant MCODEs were subjected to GO and KEGG enrichment analysis and their clinical significance was evaluated.Conclusions.By applying microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of active HE4 stimulation in EOC cells. We offered several possible mechanisms and identified therapeutic and prognostic targets of HE4 in EOC.

Download Full-text

Gene expression profiles following active HE4 stimulation in epithelial ovarian cancer cells: microarray study and comprehensive bioinformatics analysis

10.21203/rs.3.rs-100248/v1 ◽

2020 ◽

Author(s):

Liancheng Zhu ◽

Mingzi Tan ◽

Haoya Xu ◽

Bei Lin

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Coexpression Analysis ◽

Pathway Enrichment

Abstract Background: Human epididymis protein 4 (HE4) is a novel serum biomarker for diagnosing epithelial ovarian cancer (EOC) with high specificity and sensitivity, compared with CA125. Recent studies have focused on the roles of HE4 in promoting carcinogenesis and chemoresistance in EOC; however, the molecular mechanisms underlying its action remain poorly understood. This study was conducted to determine the molecular mechanisms underlying HE4 stimulation and identifying key genes and pathways mediating carcinogenesis in EOC by microarray and bioinformatics analysis.Methods: We established a stable HE4-silenced ES-2 ovarian cancer cell line labeled as “S”; the S cells were stimulated with the active HE4 protein, yielding cells labeled as “S4”. Human whole-genome microarray analysis was used to identify differentially expressed genes (DEGs) in S4 and S cells. The “clusterProfiler” package in R, DAVID, Metascape, and Gene Set Enrichment Analysis were used to perform gene ontology (GO) and pathway enrichment analysis, and cBioPortal was used for WFDC2 coexpression analysis. The GEO dataset (GSE51088) and quantitative real-time polymerase chain reaction were used to validate the results. Protein–protein interaction (PPI) network and modular analyses were performed using Metascape and Cytoscape, respectively. Results: In total, 713 DEGs were identified (164 upregulated and 549 downregulated) and further analyzed by GO, pathway enrichment, and PPI analyses. We found that the MAPK pathway accounted for a significant large number of the enriched terms. WFDC2 coexpression analysis revealed ten WFDC2-coexpressed genes (TMEM220A, SEC23A, FRMD6, PMP22, APBB2, DNAJB4, ERLIN1, ZEB1, RAB6B, and PLEKHF1) whose expression levels were dramatically altered in S4 cells; this was validated using the GSE51088 dataset. Kaplan–Meier survival statistics revealed that all 10 target genes were clinically significant. Finally, in the PPI network, 16 hub genes and 8 molecular complex detections (MCODEs) were identified; the seeds of the five most significant MCODEs were subjected to GO and KEGG enrichment analyses and their clinical relevance was evaluated.Conclusions: Through microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network following active HE4 stimulation in EOC cells. We proposed several possible mechanisms underlying the action of HE4 and identified the therapeutic and prognostic targets of HE4 in EOC.

Download Full-text

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

10.21203/rs.3.rs-29958/v1 ◽

2020 ◽

Author(s):

Zhiqiang Liu ◽

Bolong Wang

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Kegg Pathway ◽

Inflammatory Diseases ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Pharmacological Effects ◽

Ppi Network ◽

Pathway Enrichment ◽

Pharmacological Mechanism

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

Download Full-text

Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

Scientific Reports ◽

10.1038/s41598-020-78191-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Guoqing Shen ◽

Xiao Zhang ◽

Jie Gong ◽

Yang Wang ◽

Pengdan Huang ◽

...

Keyword(s):

Procambarus Clarkii ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Apoptosis Pathway ◽

Pathway Enrichment ◽

Cellular Processes ◽

Expression Of Genes ◽

Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

Download Full-text

Serum MiR-4687-3p Has Potential for Diagnosis and Carcinogenesis in Non-small Cell Lung Cancer

Frontiers in Genetics ◽

10.3389/fgene.2020.597508 ◽

2020 ◽

Vol 11 ◽

Author(s):

Man Liu ◽

Qiufang Si ◽

Songyun Ouyang ◽

Zhigang Zhou ◽

Meng Wang ◽

...

Keyword(s):

Lung Cancer ◽

Validation Cohort ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Small Cell ◽

Pathway Enrichment Analysis ◽

Small Cell Lung ◽

Invasion And Migration ◽

Pathway Enrichment ◽

And Migration

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543–0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

Download Full-text

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Cellular Physiology and Biochemistry ◽

10.1159/000485281 ◽

2017 ◽

Vol 44 (2) ◽

pp. 682-700 ◽

Cited By ~ 8

Author(s):

Lu Zhang ◽

Lan-shan Huang ◽

Gang Chen ◽

Zhen-bo Feng

Keyword(s):

Digestive Tract ◽

Digestive System ◽

Kegg Pathway ◽

Univariate Analysis ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Clinical Value ◽

Go Annotation ◽

Pathway Enrichment ◽

Target Mrnas

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

Download Full-text

Quantitative Phosphoproteomic Comparison of Lens Proteins in Highly Myopic Cataract and Age-Related Cataract

BioMed Research International ◽

10.1155/2021/6668845 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Shaohua Zhang ◽

Keke Zhang ◽

Wenwen He ◽

Yi Lu ◽

Xiangjia Zhu

Keyword(s):

Molecular Mechanisms ◽

Kegg Pathway ◽

Phosphoglycerate Kinase ◽

Enrichment Analysis ◽

Glutathione Metabolism ◽

Pathway Enrichment Analysis ◽

Phosphorylation Sites ◽

Pathway Enrichment ◽

Age Related ◽

Go Enrichment

Purpose. To investigate and compare the lens phosphoproteomes in patients with highly myopic cataract (HMC) or age-related cataract (ARC). Methods. In this study, we undertook a comparative phosphoproteome analysis of the lenses from patients with HMC or ARC. Intact lenses from ARC and HMC patients were separated into the cortex and nucleus. After protein digestion, the phosphopeptides were quantitatively analyzed with TiO2 enrichment and liquid chromatography-mass spectrometry. The potential functions of different phosphopeptides were assessed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results. In total, 522 phosphorylation sites in 164 phosphoproteins were identified. The number of phosphorylation sites was significantly higher in the cortex than in the nucleus, in both ARC and HMC lenses. The differentially phosphorylated peptides in the lens cortex and nucleus in HMC eyes were significantly involved in the glutathione metabolism pathway. The KEGG pathway enrichment analysis indicated that the differences in phosphosignaling mediators between the ARC and HMC lenses were associated with glycolysis and the level of phosphorylated phosphoglycerate kinase 1 was lower in HMC lenses than in ARC lenses. Conclusions. We provide an overview of the differential phosphoproteomes of HMC and ARC lenses that can be used to clarify the molecular mechanisms underlying their different phenotypes.

Download Full-text