Proteome Science[JOURNAL]
Sun
200 papers
Isolation and proteomic profiling of urinary exosomes from patients with colorectal cancer.
Ma L, Yu H, Zhu Y … +5 more , Xu K, Zhao A, Ding L, Gao H, Zhang M
Proteome Sci · 2023 Feb · PMID 36759883 · Full text
Exosomes in the body fluid are effective cell-derived membranous structures transferring various molecules to mediate intercellular communication. The expression of protein in the urinary exosomes from the colorectal can...
Exosomes in the body fluid are effective cell-derived membranous structures transferring various molecules to mediate intercellular communication. The expression of protein in the urinary exosomes from the colorectal cancer (CRC) patients could reflect the characteristics of tumorigenesis. The urinary exosomes with globular membrane structure, the size of 30 ~ 100 nm and positive expression of CD9, CD63 and CD81 were successfully isolated from 9 CRC patients and 3 heathy adults using the density gradient ultracentrifugation. Proteome profiles revealed by label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that several proteins were differentially expressed among different stages of CRC. Compared with normal controls, 67 proteins in CRC urinary exosomes were upregulated and 74 proteins were downregulated. The bioinformatics analysis revealed the decreased proteins were related to ESCRT III complex disassembly. The CHMP family was further determined to be the hub of interaction network of proteins enriched in ESCRT signaling. The significant decrease of CHMP4A, CHMP4B, CHMP2A, CHMP2B and CHMP1B were respectively found in the total CRC group and distant metastasis group compared with NC group. Moreover, the CEACAM family also showed significant aberrant changes in the urinary exosomes of CRC patients. The CEACAM7 and CEACAM1 were increased in the CRC patients compared with healthy individuals (P < 0.05). Significant changes of proteomic profile could be found in the urinary exosomes in the CRC patients. The differential expressed urinary exosomes derived proteins showed potential usage in diagnosis and prognosis of CRC.
Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes.
Sun X, Jiang Y, Li Q … +5 more , Tan Q, Dong M, Cai B, Zhang D, Zhao Q
Proteome Sci · 2023 Jan · PMID 36604692 · Full text
OBJECTIVE: This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocyt...
OBJECTIVE: This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocytes. METHODS: The expression level of the lncRNA Ftx in cardiomyocytes cultured in vitro was intervened, and the changes in protein levels in cardiomyocytes were quantitatively detected by liquid chromatography-mass spectrometry. The key molecules and pathways of the lncRNA-Ftx response were further examined by GO, KEGG, and protein interaction analysis. RESULTS: A total of 2828 proteins are quantified. With a 1.5-fold change threshold, 32 upregulated proteins and 49 downregulated proteins are identified in the lncRNA Ftx overexpression group, while 67 up-regulated proteins and 54 down-regulated proteins are identified in the lncRNA Ftx knockdown group. Functional clustering analysis of differential genes revealed that the lncRNA Ftx is involved in regulating cardiomyocyte apoptosis and ferroptosis and improving cellular energy metabolism. In addition, Hub genes such as ITGB1, HMGA2, STAT3, GSS, and LPCAT3 are regulated downstream by lncRNA Ftx. CONCLUSION: This study demonstrates that lncRNA Ftx plays a vital role in cardiomyocytes and may be involved in the occurrence and development of various myocardial diseases. It provides a potential target for clinical protection of the myocardium and reversal of myocardial fibrosis.
Proteomic Analysis of Protective Effects of Dl-3-n-Butylphthalide against mpp + -Induced Toxicity via downregulating P53 pathway in N2A Cells.
Zhao Y, Zhang J, Zhang Y … +6 more , Li S, Gao Y, Chang C, Liu X, Xu L, Yang G
Proteome Sci · 2023 Jan · PMID 36597095 · Full text
BACKGROUND: Dl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal mo...
BACKGROUND: Dl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD. METHOD: In our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC-MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein-protein interactions (PPI) by Cytoscape, DEPs were verified by western blot. RESULT: A total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p < 0.05). Among the 417 DEPs, 140 were upregulated and 277 were downregulated in mpp + -induced N2A cells with NBP pretreatment. KEGG pathway analysis indicated that lysosome, phagosome, apoptosis, endocytosis and ferroptosis are the mainly enriched pathways. By using MCL clustering in PPI analysis, 48 clusters were generated and the subsequent KEGG analysis of the top 3 clusters revealed that P53 signaling pathway was recognized as the dominant pathway for NBP treatment. CONCLUSION: NBP significantly relived mpp + -induced cell toxicity. The neuroprotective role of NBP was implicated with P53 signaling pathway in some extent. These findings will reinforce the understanding of the mechanism of NBP in PD and identify novel therapeutic targets.
Responses of the tree peony (Paeonia suffruticosa, Paeoniaceae) cultivar 'Yu Hong' to heat stress revealed by iTRAQ-based quantitative proteomics.
Ma J, Wang Q, Wei LL … +4 more , Zhao Y, Zhang GZ, Wang J, Gu CH
Proteome Sci · 2022 Dec · PMID 36578066 · Full text
Horticulture productivity has been increasingly restricted by heat stress from growing global warming, making it far below the optimum production capacity. As a popular ornamental cultivar of tree peony, Paeonia suffruti...
Horticulture productivity has been increasingly restricted by heat stress from growing global warming, making it far below the optimum production capacity. As a popular ornamental cultivar of tree peony, Paeonia suffruticosa 'Yu Hong' has also been suffering from heat stress not suitable for its optimal growth. To better understand the response mechanisms against heat stress of tree peony, investigations of phenotypic changes, physiological responses, and quantitative proteomics were conducted. Phenotypic and physiological changes indicated that 24 h of exposure to heat stress (40 °C) was the critical duration of heat stress in tree peony. The proteomic analyses revealed a total of 100 heat-responsive proteins (HRPs). According to bioinformatic analysis of HRPs, the heat tolerance of tree peony might be related to signal transduction, synthesis/degradation, heat kinetic proteins, antioxidants, photosynthesis, energy conversion, and metabolism. Our research will provide some new insights into the molecular mechanism under the response against the heat stress of tree peony, which will benefit the future breeding of heat-resistant ornamental plants.
TMT-based quantitative proteomics analysis of the effects of Jiawei Danshen decoction myocardial ischemia-reperfusion injury.
Zhu XM, Tan Y, Shi YH … +4 more , Li Q, Zhu J, Liu XD, Tong QZ
Proteome Sci · 2022 Dec · PMID 36517846 · Full text
BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influ...
BACKGROUND: Every year, approximately 17 million people worldwide die due to coronary heart disease, with China ranking second in terms of the death toll. Myocardial ischemia-reperfusion injury (MIRI) significantly influences cardiac function and prognosis in cardiac surgery patients. Jiawei Danshen Decoction (JWDSD) is a traditional Chinese herbal prescription that has been used clinically for many years in China to treat MIRI. The underlying molecular mechanisms, however, remain unknown. To investigate the proteomic changes in myocardial tissue of rats given JWDSD for MIRI therapy-based proteomics. METHODS: MIRI rat model was created by ligating/releasing the left anterior descending coronary artery. For seven days, the drugs were administered twice daily. The model was created following the last drug administration. JWDSD's efficacy in improving MIRI was evaluated using biochemical markers and cardiac histology. Tandem mass tag-based quantitative proteomics (TMT) technology was also used to detect proteins in the extracted heart tissue. To analyze differentially expressed proteins (DEPs), bioinformatics analysis, including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways, were employed. Furthermore, western blotting confirmed the potential targets regulated by JWDSD. RESULTS: The histopathologic characteristics and biochemical data showed JWDSD's protective effects on MIRI rats. A total of 4549 proteins were identified with FDR (false discovery rate) ≤1%. Twenty overlapping were identified (162 DEPs and 45 DEPs in Model/Control or JWDSD/Model group, respectively). Of these DEPs, 16 were regulated by JWDSD. GO analysis provided a summary of the deregulated protein expression in the categories of biological process (BP), cell component (CC), and molecular function (MF). KEGG enrichment analysis revealed that the signaling pathways of neutrophil extracellular trap formation, RNA polymerase, serotonergic synapse, and linoleic acid metabolism are all closely related to JWDSD effects in MIRI rats. Furthermore, T-cell lymphoma invasion and metastasis 1 (TIAM1) was validated using western blotting, and the results were consistent with proteomics data. CONCLUSIONS: Our study suggests that JWDSD may exert therapeutic effects through multi-pathways regulation in MIRI treatment. This work may provide proteomics clues for continuing research on JWDSD in treating MIRI.
Profiles of transcriptome and metabolic pathways after hypobaric hypoxia exposure.
Xu J, Chen WJ, Wang Z … +7 more , Xin MY, Gao SH, Liu WJ, Wang KK, Ma JW, Yan XZ, Ren YM
Proteome Sci · 2022 Sep · PMID 36153524 · Full text
BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pat...
BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.
A combined protein toxin screening based on the transcriptome and proteome of Solenopsis invicta.
Cai L, Yang F, Wang Y … +7 more , Yang J, Zhu Y, Ma X, Höfer J, Wang Y, Ma Y, Xiao L
Proteome Sci · 2022 Sep · PMID 36131344 · Full text
BACKGROUND: Multi-omics technology provides a good tool to analyze the protein toxin composition and search for the potential pathogenic factors of Solenopsis invicta, under the great harm of the accelerated invasion in...
BACKGROUND: Multi-omics technology provides a good tool to analyze the protein toxin composition and search for the potential pathogenic factors of Solenopsis invicta, under the great harm of the accelerated invasion in southern China. METHODS: Species collection, functional annotation, toxin screening, and 3D modeling construction of three interested toxins were performed based on the successfully constructed transcriptome and proteome of S. invicta. RESULTS: A total of 33,231 unigenes and 721 proteins were obtained from the constructed transcriptome and proteome, of which 9,842 (29.62%) and 4,844 (14.58%) unigenes, as well as 469 (65.05%) and 71 (99.45%) proteins were annotated against the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. After comparing with the uniprot toxin database, a total of 316 unigenes and 47 proteins (calglandulin, venom allergen 3, and venom prothrombin activator hopsarin-D, etc.) were successfully screened. CONCLUSIONS: The update of annotations at the transcriptome and proteome levels presents a progression in the comprehension of S. invicta in China. We also provide a protein toxin list that could be used for further exploration of toxicity as well as its antagonistic strategy by S. invicta.
Effect of downregulated citrate synthase on oxidative phosphorylation signaling pathway in HEI-OC1 cells.
Xu X, Liu Y, Luan J … +7 more , Liu R, Wang Y, Liu Y, Xu A, Zhou B, Han F, Shang W
Proteome Sci · 2022 Sep · PMID 36071491 · Full text
BACKGROUND: Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular a...
BACKGROUND: Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular and molecular mechanisms related to hearing lose. We previously reported the increased apoptosis and the accumulation of reactive oxygen species in shRNACs-1429 cells, a Cs low-expressed cell model from HEI-OCI. The details of the mechanism of ROS production and apoptosis mediated by the abnormal expression of Cs needed to research furtherly. METHODS: iTRAQ proteomics was utilized to detect the differentially expressed proteins (DEPs) caused by low expression of Cs. The GO and KEGG pathways analysis were performed for annotation of the differentially expressed proteins. Protein-protein interaction network was constructed by STRING online database. Immunoblotting was utilized to confirm the protein levels of the the differentially expressed proteins. RESULTS: The differentially expressed proteins were significantly enriched in various signaling pathways mainly related to mitochondrial dysfunction diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, et al. Most noteworthy, the oxidative phosphorylation pathway was most significantly suppressed in the shRNACs-1429 cells,, in which a total of 10 differentially expressed proteins were enriched and were all downregulated by the abnormal expression of Cs. The downregulations of Ndufb5, Ndufv1 and Uqcrb were confirmed by immunoblotting. Meanwhile, the ATP levels of shRNACs-1429 cells were also reduced. CONCLUSIONS: These results suggest that low level expression of Cs induces the inhibition of oxidative phosphorylation pathway, which is responsible for the high level production of reactive oxygen species and low level of ATP, leading to the apoptosis of cochlear cells. This study may provide new theories for understanding and therapy of progressive hearing loss.
Tear proteomics analysis of patient suffered from delayed mustard gas keratopathy.
Parvin S, Shahriary A, Aghamollaei H … +6 more , Gh BFNM, Bagheri H, Ghanei M, Daryabari SH, Jadidi K, Arabfard M
Proteome Sci · 2022 Aug · PMID 35948930 · Full text
Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to ana...
Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision.
Phosphoproteome profiling of mouse liver during normal aging.
Liu JF, Wu Y, Yang YH … +4 more , Wu SF, Liu S, Xu P, Yang JT
Proteome Sci · 2022 Aug · PMID 35932011 · Full text
BACKGROUND: Aging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discove...
BACKGROUND: Aging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discover potential intervention methods. Old mice are frequently obese with a fatty liver. METHODS: We applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of the liver in mice aged 2 or 18 months. MaxQuant was used for quantitative analysis and PCA was used for unsupervised clustering. RESULTS: Through phosphoproteome analysis, a total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. PCA analysis of both the phosphoproteome and transcriptome data could distinguish young and old mice. However, from kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis done with phosphoproteome data, we observed high phosphorylation of fatty acid biosynthesis, β-oxidation, and potential secretory processes, together with low phosphorylation of the Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to the aging-associated fatty liver phenotype than the differentially expressed transcripts. The phosphoproteome may reveal distinctive biological functions that are lost in the transcriptome. CONCLUSIONS: In summary, we constructed a phosphorylation-associated network in the mouse liver during normal aging, which may help to discover novel antiaging strategies.
A risk score model based on TGF-β pathway-related genes predicts survival, tumor microenvironment and immunotherapy for liver hepatocellular carcinoma.
Liao J, Liu Q, Chen J … +3 more , Lu Z, Mo H, Jia J
Proteome Sci · 2022 Jun · PMID 35733217 · Full text
BACKGROUND: Transforming growth factor-beta (TGF-β) signal is an important pathway involved in all stages of liver hepatocellular carcinoma (LIHC) initiation and progression. Therefore, targeting TGF- β pathway may be a...
BACKGROUND: Transforming growth factor-beta (TGF-β) signal is an important pathway involved in all stages of liver hepatocellular carcinoma (LIHC) initiation and progression. Therefore, targeting TGF- β pathway may be a potential therapeutic strategy for LIHC. Prediction of patients' tumor cells response requires effective biomarkers. METHODS: From 54 TGF-β-related genes, this research determined the genes showing the greatest relation to LIHC prognosis, and developed a risk score model with 8 TGF-β-related genes. The model divided LIHC patients from different datasets and platforms into low- and high-risk groups. Multivariate Cox regression analysis confirmed that the model was an independent prognostic factor for LIHC. The differences in genetic mutation, immune cell infiltration, biological pathway, response to immunotherapy or chemotherapy, and tumor microenvironment in LIHC samples showing different risks were analyzed. RESULTS: Compared with low-risk group, in the training set and test set, high-risk group showed shorter survival, lower stromal score and higher M0 macrophages scores, regulatory T cells (Tregs), helper follicular T cells. Moreover, high-risk samples showed higher sensitivity to cisplatin, imatinib, sorafenib and salubrinal and pyrimethamine. High-risk group demonstrated a significantly higher Tumor Immune Dysfunction and Exclusion (TIDE) score, but would significantly benefit less from taking immunotherapy and was less likely to respond to immune checkpoint inhibitors. CONCLUSIONS: In general, this work provided a risk scoring model based on 8 TGF-β pathway-related genes, which might be a new potential tool for predicting LIHC.
Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.
Wen XP, Long G, Zhang YZ … +3 more , Huang H, Liu TH, Wan QQ
Proteome Sci · 2022 Jun · PMID 35681168 · Full text
BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pu...
BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. METHODS: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. RESULTS: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). CONCLUSIONS: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.
A novel nanobody as therapeutics target for EGFR-positive colorectal cancer therapy: exploring the effects of the nanobody on SW480 cells using proteomics approach.
Lamtha T, Krobthong S, Yingchutrakul Y … +4 more , Samutrtai P, Gerner C, Tabtimmai L, Choowongkomon K
Proteome Sci · 2022 May · PMID 35578244 · Full text
BACKGROUND: The epidermal growth factor receptor (EGFR) overexpression is found in metastatic colorectal cancer (mCRC). Targeted molecular therapies such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TK...
BACKGROUND: The epidermal growth factor receptor (EGFR) overexpression is found in metastatic colorectal cancer (mCRC). Targeted molecular therapies such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKI) are becoming more precise, targeting specifically for cancer therapeutics. However, there are adverse effects of currently available anti-EGFR drugs, including drug-resistant and side effects. Nanobodies can overcome these limitations. Our previous study has found that cell-penetrable nanobodies targeted at EGFR-tyrosine kinase were significantly reduced EGFR-positive lung cancer cells viability and proliferation. The aim of the present study was to determine the effect of cell-penetrable nanobody (R9VH36) on cell viability and proteomic profile in EGFR-positive human colorectal cancer cell lines. METHODS: The human colorectal carcinoma cell line (SW480) was treated with R9VH36, compared with gefitinib. Cell viability was monitored using the MTT cell viability assay. The proteomic profiling was analyzed by LC-MS/MS . RESULTS: The half-maximal inhibitory concentration (IC) values determined for R9VH36 and gefitinib against SW480 were 527 ± 0.03 nM and 13.31 ± 0.02 μM, respectively. Moreover, both the gefitinib-treated group and nanobody-treated group had completely different proteome profiles. A total 6626 differentially expressed proteins were identified. PCA analysis revealed different proteome profiling in R9VH36 experiment. There were 8 proteins in R9VH36 that significantly exhibited opposite expression directions when compared to gefitinib. These proteins are involved in DNA-damage checkpoint processes. CONCLUSION: The proteomics explored those 6,626 proteins had different expressions between R9VH36 and gefitinib. There were 8 proteins in R9VH36 exhibited opposite expression direction when comparing to gefitinib. Our findings suggest that R9VH36 has the potential to be an alternative remedy for treating EGFR-positive colon cancer.
Quantitative proteomic analysis of cerebrospinal fluid reveals CD163, A2M and full-length APP as potential diagnostic biomarkers of paediatric bacterial meningitis.
Luo T, Yang S, Chen Y … +8 more , Liu S, Yang L, Hu N, Ma Y, Qiu J, Wang K, Li L, Tan L
Proteome Sci · 2022 May · PMID 35524265 · Full text
BACKGROUND: Bacterial meningitis (BM) is a life-threatening infectious disease of the central nervous system in infants and children. To date, no diagnostic methods for the early and precise diagnosis of paediatric BM ha...
BACKGROUND: Bacterial meningitis (BM) is a life-threatening infectious disease of the central nervous system in infants and children. To date, no diagnostic methods for the early and precise diagnosis of paediatric BM have been developed. METHODS: A label-free cerebrospinal fluid (CSF) quantitative proteomic analysis of 8 patients with confirmed or suspected BM, 9 patients with confirmed or suspected viral meningitis (VM) and 6 non-CNS-infected hospital patients was performed via high-resolution LC-MS/MS. RESULTS: Our CSF proteomic analysis allowed the identification of critical differences between the BM and non-BM groups. Compared to the proteomes of the non-BM groups, the proteome of the paediatric BM group was characterized by upregulation of complement and coagulation cascades, regulation of IGF transport, uptake by IGF-binding proteins and acute inflammatory response, downregulation of developmental growth, and metabolism of carbohydrates. Moreover, the levels of CD163, A2M and full-length APP in CSF showed excellent diagnostic performance for paediatric BM, with AUC values of 0.911 (95% CI: 0.839-0.984), 0.908 (95% CI: 0.816-1.000) and 0.944 (95% CI: 0.86, 1.000), respectively. Among them, A2M and full-length APP are reported here for the first time as potential diagnostic biomarkers of BM. The findings imply that peptidase regulator activity plays an important role in BM and provide potential novel targets for precision medicine in paediatric BM. CONCLUSIONS: CD163, A2M and full-length APP are validated as potential diagnostic biomarkers of paediatric BM.
Long noncoding RNA Ftx regulates the protein expression profile in HCT116 human colon cancer cells.
Jia R, Song L, Fei Z … +2 more , Qin C, Zhao Q
Proteome Sci · 2022 Apr · PMID 35490216 · Full text
BACKGROUND: The long noncoding RNA (lncRNA) five prime to Xist (Ftx) is involved in distant metastasis in colorectal cancer (CRC). This study aimed to investigate Ftx alteration-induced proteomic changes in the highly me...
BACKGROUND: The long noncoding RNA (lncRNA) five prime to Xist (Ftx) is involved in distant metastasis in colorectal cancer (CRC). This study aimed to investigate Ftx alteration-induced proteomic changes in the highly metastatic CRC cell line HCT116. METHODS: Tandem mass tag (TMT)-based proteomics analysis was performed to detect the differential protein expression in Ftx-overexpressing and Ftx-silenced HCT116 cells. The differentially expressed proteins were classified and characterized by bioinformatics analyses, including gene ontology (GO) annotation, GO/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway/protein domain enrichment analyses, as well as hierarchical clustering. A total of 5471 proteins were quantified, and the proteins with |fold change|≥ 1.2 and p < 0.05 were identified as differentially expressed proteins in response to Ftx overexpression or silencing. RESULTS: The bioinformatics analyses revealed that the differentially expressed proteins were involved in a wide range of GO terms and KEGG signaling pathways and contained multiple protein domains. These terms, pathways, and protein domains were associated with tumorigenesis and metastasis in CRC. CONCLUSIONS: Our results indicate that the alteration of Ftx expression induces proteomic changes in highly metastatic HCT116 cells, suggesting that Ftx and its downstream molecules and signaling pathways could be potential diagnostic biomarkers and therapeutic targets for metastatic CRC.
TMT-based proteomics analysis of the cerebral cortex of TauT knockout rats.
Xia Y, Huang X, Mo L … +3 more , Wang C, Fan W, Huang H
Proteome Sci · 2022 Apr · PMID 35468821 · Full text
BACKGROUND: Taurine serves a variety of nutritional and physiological roles, and it is mostly transported in cells via taurine transporter (TauT). The effect of taurine transporter in cerebral cortex is still unknown. We...
BACKGROUND: Taurine serves a variety of nutritional and physiological roles, and it is mostly transported in cells via taurine transporter (TauT). The effect of taurine transporter in cerebral cortex is still unknown. We employed TMT label-based proteomics to find differences in proteins in the cerebral cortex of TauT knockout rats in this investigation. The goal of this research was to see how TauT deletion affected protein alterations in brain tissue and to see if there was a new research area for TauT. METHODS: The cerebral cortex of TauT knockout rats and wild-type control rats were analyzed using TMT-based proteomics, and differentially expressed proteins were analyzed by bioinformatics analysis means such as GO and KEGG, the association between the proteins was found by PPI, and biologically significant and interesting proteins were selected for verification by WB and immunohistochemistry. RESULTS: There were total of 8275 proteins found, but only 35 differentially expressed proteins were identified (27 up-regulated and 8 down-regulated), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathways and functional classification of the proteins. The results show that these differentially expressed proteins are mainly enriched in lysine degradation, cell cycle, chronic myeloid leukemia, and longevity regulating pathways-multiple species, renal cell carcinoma, pathways in cancer, etc. To verify the proteomic data, we analyzed the expression of Annexin6 and Pik3r2 by western blotting and immunofluorescence. The results are consistent with proteomics, which proves the reliability of our proteomics data. CONCLUSION: Through TMT-based proteomics, we have a comprehensive understanding of the effect of TauT knockout on the changes of other proteins in the cerebral cortex, providing new evidence for further understanding the function of TauT.
Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer.
Li L, Liu H, Li Y … +5 more , Guo C, Wang B, Shen D, Zhang Q, Ding C
Proteome Sci · 2022 Apr · PMID 35397555 · Full text
BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients' prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterizat...
BACKGROUND: The surveillance and therapy of early-stage cancer would be better for patients' prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. METHODS: In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). RESULTS: We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. CONCLUSION: We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.
Predicting protein-protein interactions between banana and Fusarium oxysporum f. sp. cubense race 4 integrating sequence and domain homologous alignment and neural network verification.
Fang H, Zhong C, Tang C
Proteome Sci · 2022 Mar · PMID 35351140 · Full text
BACKGROUND: The pathogen of banana Fusarium oxysporum f. sp. cubense race 4(Foc4) infects almost all banana species, and it is the most destructive. The molecular mechanism of the interactions between Fusarium oxysporum...
BACKGROUND: The pathogen of banana Fusarium oxysporum f. sp. cubense race 4(Foc4) infects almost all banana species, and it is the most destructive. The molecular mechanism of the interactions between Fusarium oxysporum and banana still needs to be further investigated. METHODS: We use both the interolog and domain-domain method to predict the protein-protein interactions (PPIs) between banana and Foc4. The predicted protein interaction sequences are encoded by the conjoint triad and autocovariance method respectively to obtain continuous and discontinuous information of protein sequences. This information is used as the input data of the neural network model. The Long Short-Term Memory (LSTM) neural network five-fold cross-validation and independent test methods are used to verify the predicted protein interaction sequences. To further confirm the PPIs between banana and Foc4, the GO (Gene Ontology) and KEGG (Kyoto Encylopedia of Genes and Genomics) functional annotation and interaction network analysis are carried out. RESULTS: The experimental results show that the PPIs for banana and foc4 predicted by our proposed method may interact with each other in terms of sequence structure, GO and KEGG functional annotation, and Foc4 protein plays a more active role in the process of Foc4 infecting banana. CONCLUSIONS: This study obtained the PPIs between banana and Foc4 by using computing means for the first time, which will provide data support for molecular biology experiments.
Identification and validation of serum autoantibodies in children with B-cell acute lymphoblastic leukemia by serological proteome analysis.
Yu R, Yang S, Liu Y … +1 more , Zhu Z
Proteome Sci · 2022 Feb · PMID 35109855 · Full text
BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. Even though significant progresses have been made in the treatment of B-ALL, some pediatric B-ALL have still poor progno...
BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. Even though significant progresses have been made in the treatment of B-ALL, some pediatric B-ALL have still poor prognosis. The identification of tumor autoantibodies may have utility in early cancer diagnosis and immunotherapy. In this study, we used serological proteome analysis (SERPA) to screen serum autoantibodies of pediatric B-ALL, aiming to contribute to the early detection of B-ALL in children. METHODS: The total proteins from three pooled B-ALL cell lines (NALM-6, REH and BALL-1 cells) were separated using two-dimensional gel electrophoresis (2-DE), which was followed by Western blot by mixed serum samples from children with B-ALL (n=20) or healthy controls (n=20). We analyzed the images of 2-D gel and Western blot by PDQuest software, and then identified the spots of immune responses in B-ALL samples compared with those in control samples. The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against alpha-enolase (α-enolase) and voltage-dependent anion-selective channel protein 1 (VDAC1) were further validated in sera from another 30 children with B-ALL and 25 normal individuals by the use of enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis. RESULTS: Utilizing the SERPA approach, α-enolase and VDAC1 were identified as candidate autoantigens in children with B-ALL. The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23% by using ELISA analysis, respectively, which were significantly higher than those in normal controls (4% and 0, p<0.05). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. CONCLUSIONS: This study incidated that α-enolase and VDAC1 may be the autoantigens associated with B-ALL. Therefore, α-enolase and VDAC1 autoantibodies may be the potential serological markers for children with B-ALL.
Analysis of plasma proteins using 2D gels and novel fluorescent probes: in search of blood based biomarkers for Alzheimer's disease.
Laffoon SB, Doecke JD, Roberts AM … +13 more , Vance JA, Reeves BD, Pertile KK, Rumble RL, Fowler CJ, Trounson B, Ames D, Martins R, Bush AI, Masters CL, Grieco PA, Dratz EA, Roberts BR
Proteome Sci · 2022 Jan · PMID 35081972 · Full text
BACKGROUND: The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yie...
BACKGROUND: The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer's disease. METHODS: The concentration of proteins in plasma covers a vast range of 12 orders of magnitude. Therefore, to search for medium to low abundant biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL. RESULTS: We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a preliminary validation study, on unique individual samples compared to the discovery cohort, using a targeted LC-MS/MS assay on a subset of discovered biomarkers. We found that targets that displayed a high degree of isoform specific changes in the 2D gels were not changed in the targeted MS assay which reports on the total level of the biomarker. CONCLUSIONS: This demonstrates that further development of mass spectrometry assays is needed to capture the isoform complexity that exists in theses biological samples. However, this study indicates that a peripheral protein signature has potential to aid in the characterization of AD.
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