Comparative Proteomic Analysis Reveals Novel Biomarkers for Gastric Cancer in South Indian Tamil Population

2021 ◽  
Vol 24 ◽  
Author(s):  
Ananthi Sivagnanam ◽  
Balasankar Thangasamy ◽  
Vignesh Nagarajan ◽  
Subeksha Govindarajan Ravi ◽  
Jeevitha Chithra Madhesh ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Detection ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Serum Samples ◽  
Two Dimensional Gel Electrophoresis ◽  
South Indian ◽  
Novel Biomarkers

Background: Gastric cancer (GC) remains a major global health problem due to a poor understanding of its progression at the molecular level and a lack of early detection or diagnosis. Early detection is highly crucial for improving prognosis. The incidence of GC is very high in countries like India due to the limitations among the established biomarkers for GC owing to poor sensitivity and specificity. Objective: To identify the novel biomarkers from serum samples obtained from GC patients when compared with healthy subjects. Methods: Serum samples from GC patients were analyzed by two-dimensional gel electrophoresis (2DGE) coupled with tandem mass spectrometry (MS), including both matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) and liquid chromatography-MS (LC-MS/MS) analysis. Identified proteins were further analyzed by gene ontology and protein interaction studies. Results: A total of 73 protein spots were detected in 2DGE image analysis. Among them, seven differentially-expressed proteins were identified using MS analyses, which included serotransferrin/transferrin, albumin, ceruloplasmin, C-reactive protein (CRP), fibrinogen γ-chain (FGG), and two unreported novel proteins, immunoglobulin kappa constant (IgκC) region and Homo sapiens zinc finger protein 28 (ZNF28) homolog. Among these proteins, serotransferrin, albumin, ceruloplasmin, FGG, and ZNF28 were down-regulated in GC samples (p < 0.05), while IgκC region and CRP were up-regulated significantly. Conclusion: Most of the differentially expressed proteins were involved in angiogenesis, plasminogen-activating cascade, and blood coagulation pathways which are known to play a critical role in gastric tumorigenesis. Our current results provide a panel of candidate biomarkers for GC with novel biomarkers which were not reported earlier.

scholarly journals iTRAQ Quantitative Analysis of Multidrug Resistance Mechanisms in Human Gastric Cancer Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Huai-Dong Hu ◽  
Feng Ye ◽  
Da-Zhi Zhang ◽  
Peng Hu ◽  
Hong Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Absolute Quantification ◽  
Differentially Expressed ◽  
Human Gastric Cancer ◽  
Differentially Expressed Proteins ◽  
Gastric Cancer Cells ◽  
Proteomic Approach

Multidrug resistance (MDR) is a major obstacle towards a successful treatment of gastric cancer. However, the mechanisms of MDR are intricate and have not been fully understood. To elucidate the molecular mechanisms of MDR in gastric cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the vincristine-resistant SGC7901/VCR cell line and its parental SGC7901 cell line as a model. In total, 820 unique proteins were identified and 91 proteins showed to be differentially expressed in SGC7901/VCR compared with SGC7901. Several differentially expressed proteins were further validated by western blot analysis. Furthermore, the association of MVP, one of the highly expressed proteins in SGC7901/VCR, with MDR was verified. Our study is the first application of iTRAQ technology for MDR mechanisms analysis in gastric cancer, and many of the differentially expressed proteins identified have not been linked to MDR in gastric cancer before, which showed the value of this technology in identifying differentially expressed proteins in cancer.

Proteomics Analysis of Bone Marrow Cells of Acute Myeloid Leukemia (M2a) and Its Prognosis Significance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4297-4297
Author(s):  
Fan Yi Meng ◽  
Shuai Tian ◽  
Jia-ming Tang
Keyword(s):  
Bone Marrow ◽  
Zinc Finger Protein ◽  
Differentially Expressed ◽  
Leukemic Cells ◽  
Differentially Expressed Proteins ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Group A ◽  
Group B ◽  
Tof Ms

Abstract Objective:The distinct proteins of leukemic cells were investigated by proteomics technology between AML-M2a patients before inductive treatments with evidently different duration of first continuous complete remission(CCR1) and AML-M2a patients at replase in order to find their relations with prognosis of AML-M2a. Methods:The bone marrow mononuclear cells(BMMNCs) from 17 cases of AML-M2a patients before inductive treatment were grouped with different duration of CCR1: group A with CCR1 duration exceeded 12 months(11 cases), group B within 6 months(6 cases), and group C was composed of 3 patients at replase among group B. The proteins of BMMNCs from all the patients were separated by two-dimensional electrophoresis, and the part of differentially-expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS). Results: 6 differentially-expressed proteins were identified between group A and B by MALDI-TOF-MS: tubulin-specific chaperone B, myeloperoxidase, &lt;TT&gt;Solution Structure Of The Ch Domain Of Human Transgelin-2,&lt;/TT&gt; glutathione S-transferase, RING zinc finger protein, glyceraldehyde-3-phosphate dehydrogenase.3 differentially-expressed proteins were identified in group C: NAD(P)H dehydrogenase, hypothetical protein, HES1. Conclusion: The distinct proteins of leukemic cells of AML-M2a patients before inductive treatments were involved in prognosis, and the proteins of BMMNCs from patients at replase have changed.

Proteomic profile of primary isolated rat mesangial cells in high-glucose culture condition and decreased expression of PSMA6 in renal cortex of diabetic ratsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 635-648 ◽  
Author(s):  
Zhiguo Li ◽  
Haojun Zhang ◽  
Xi Dong ◽  
Frank J. Burczynski ◽  
Patrick Choy ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
High Glucose ◽  
Gel Electrophoresis ◽  
Renal Cortex ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Isolated Rat

Diabetic nephropathy (DN) is one of the most important complications of diabetic patients and is characterized histologically by an accumulation of extracellular matrix (ECM) protein in the glomerular mesangium. Therefore, mesangial cells likely play an important role in the development of diabetic nephropathy. Here, we employed proteomic techniques to investigate the protein profile of rat mesangial cells under high-glucose culture conditions. Primary isolated rat glomerular mesangial cells were cultured under different concentrations of glucose (5.4 mmol·L–1 for normal control and 30 mmol·L–1 for high glucose) for 0, 8, 16, and 72 h, as well as for 25 days. Cellular total proteins were isolated from these cells and employed for two-dimensional gel electrophoresis (2-DE). Differentially expressed proteins were identified by matrix-assisted laser desorption – ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and some of these proteins were documented in rat models of diabetes by Western blot. Rat mesangial cells were successfully isolated in the laboratory and their proliferation rates were significantly inhibited by high glucose. Two-dimensional gel electrophoresis analyses revealed 28 differentially expressed protein spots between the normal and high-glucose groups. After MALDI-TOF-MS analysis, all 28 protein spots were successfully identified with the peptide mass fingerprint (PMF) method. Representatively, SOD1, PCBP1 and PSMA6 were validated by Western blot analysis following protein extractions from the normal and high-glucose groups. Abundance of these proteins was consistent with that found in 2-DE. Moreover, expression of SOD1, PCBP1, and PSMA6 in renal cortex was further examined in two rat models of diabetes (streptozotocin-induced and spontaneous OLETF diabetic models). Abundance of SOD1 and PCBP1 proteins did not show any significant difference between normal control and diabetic rats. However, abundance of the PSMA6 protein was significantly reduced in the renal cortex of both STZ-induced and spontaneous OLETF diabetic rats. Proteomic analysis identified 28 differentially expressed proteins in primary isolated rat mesangial cells between normal and high glucose treatments. Expression of one identified protein was found to be consistent with expression in the renal cortex of two rat diabetic models. Therefore, identification of protein expression patterns in mesangial cells can be employed to develop a therapeutic target for treatment of diabetic nephropathy.

scholarly journals Proteomic Profiling of Plasma-Derived Biomarkers in Patients with Bladder Cancer: A Step towards Clinical Translation

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1294
Author(s):  
Taoufik Nedjadi ◽  
Nada Albarakati ◽  
Hicham Benabdelkamel ◽  
Afshan Masood ◽  
Assim A. Alfadda ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Early Detection ◽  
Disease Progression ◽  
Apolipoprotein A1 ◽  
Differentially Expressed ◽  
2D Electrophoresis ◽  
Differentially Expressed Proteins ◽  
Invasive Phenotype ◽  
Cancer Pathogenesis ◽  
Muscle Invasive

Background: Bladder cancer is a life-threatening disease and a major cause of cancer-associated complications. The main challenges confronted during the clinical management of bladder cancer are associated with recurrence and disease progression to the muscle-invasive phenotype. Improved early detection of the disease is of paramount importance to prevent disease progression and improve survival. Hence, novel clinically applicable biomarkers for early detection are warranted. Methods: In the current study, a comparative proteomic approach was undertaken using plasma samples to identify protein biomarkers associated with the muscle-invasive phenotype of bladder carcinoma. Isolated plasma proteins were depleted, DIGE-labeled, then subjected to conventional 2D electrophoresis followed by mass spectrometry for identification of differentially expressed proteins. Western blot was used for data validation. Results: Fourteen differentially expressed proteins with statistically significant changes in abundance between the cancer group and control group were identified. Three differentially expressed proteins were selected for validation, among which apolipoprotein A1 exhibited high specificity and sensitivity (AUC = 0.906). Ingenuity pathway analysis identified IFN-γ and TNF-α as the main signaling hub for the differentially regulated proteins. Conclusion: Our findings provide additional insight into understanding bladder cancer pathogenesis. Our data identified potential non-invasive plasma-derived biomarker proteins that merit additional investigation to validate its clinical usefulness to prevent bladder cancer progression.

scholarly journals Identification of Differentially Expressed Proteins in the Serum for Systemic Juvenile Idiopathic Arthritis Using Next-generation Proteomics

2021 ◽  
Author(s):  
Hironori Sato ◽  
Yuzaburo Inoue ◽  
Yusuke Kawashima ◽  
Daisuke Nakajima ◽  
Ren Nakamura ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Active Phase ◽  
Differentially Expressed ◽  
Heme Oxygenase 1 ◽  
Differentially Expressed Proteins ◽  
Serum Samples ◽  
Core Proteins ◽  
Morphogenetic Protein ◽  
Frequent Relapses

Abstract Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease caused by high production of inflammatory cytokines. Conventional biomarkers, such as IL-18 are reportedly not always associated with frequent relapses or complication with macrophage activation syndrome (MAS). As few specific biomarkers that can indicate and evaluate the sJIA disease activity have been identified, the discovery of biomarkers is very important. We performed a deep proteomic analysis of serum samples from nine patients with sJIA using highly sensitive mass spectrometry, and identified differentially expressed proteins in various disease phases. We selected 68 proteins (URPs) that were highly expressed in the active phase from total of 2,727 proteins. Pathway analysis revealed that the URPs included proteins related to many immune process and proteasome proteins, which might be associated with the pathogenesis of sJIA. Based on these results, four proteins (leucine aminopeptidase 3; LAP3, guanylate-binding protein 1; GBP1, Heme oxygenase 1; HMOX1, and bone morphogenetic protein 10; BMP10), which exhibit high fold changes during the active phase or which might be core proteins in the functional network were selected as candidate biomarkers. These proteins may be clinically useful for diagnostic and therapeutic purposes and might help determine the pathogenesis of the disease.

scholarly journals Quantitative Analysis of Methylated Adenosine Modifications Revealed Increased Levels of N6-Methyladenosine (m6A) and N6,2′-O-Dimethyladenosine (m6Am) in Serum From Colorectal Cancer and Gastric Cancer Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Yiqiu Hu ◽  
Zhihao Fang ◽  
Jiayi Mu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastric Cancer ◽  
Quantitative Analysis ◽  
Early Detection ◽  
Human Serum ◽  
Cancer Patients ◽  
Healthy Controls ◽  
Serum Samples ◽  
Gastrointestinal Malignancies ◽  
Gastric Cancer Patients

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.

scholarly journals Identification of Key Genes and MicroRNAs in Gastric Cancer via miRNA-mRNA Regulatory Network

2020 ◽  
Author(s):  
Chao Huang ◽  
Xiaojian Zhu ◽  
Jiefeng Zhao ◽  
Fanqin Bu ◽  
Jun Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Molecular Markers ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Receptor Interactions

Abstract Background Gastric cancer (GC) is a malignant tumor with high mortality. MicroRNAs (miRNAs) participate in various biological processes and disease pathogenesis by targeting messenger RNA (mRNA). The purpose of this study was to identify potential prognostic molecular markers of GC and to characterize the molecular mechanisms of GC. Methods A gene expression profiling dataset (GSE54129) and miRNA expression profiling dataset (GSE113486) were downloaded from the Gene Expression Omnibus (GEO) database. A miRNA-mRNA interaction network was established. Functional and pathway enrichment analyses were performed for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using FunRich, the clusterProfiler package, and DIANA-mirPath. Survival analysis of key molecular markers was performed using the online tool Kaplan-Meier Plotter and the database OncomiR. Finally, experiments were carried out to verify the expression levels and biological functions of a key gene. Results A total of 390 DEMs and 341 DEGs were identified. Ultimately, 45 genes and 31 miRNAs were selected to establish a miRNA-mRNA regulatory network. Four hub genes (ZFPM2, FUT9, NEUROD1 and LIPH) and six miRNAs (hsa-let-7d-5p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-133b, hsa-miR-130a-3p and hsa-miR-124-3p) were identified in the network. DEGs and DEMs were associated with ECM-receptor interactions and metabolic pathways. Two genes (ZFPM2 and LIPH) and two miRNAs (hsa-miR-23a-3p and hsa-miR-130a-3p) were observed to be related to the prognosis of GC. ZFPM2 was highly expressed in GC tissues and various GC cell lines and could promote the proliferation, invasion and migration of GC cells. Conclusion The expression levels of ZFPM2, LIPH, hsa-miR-23a-3p and hsa-miR-130a-3p were closely related to the prognosis of GC. ZFPM2 may serve as a potential molecular marker and therapeutic target for GC. ECM receptor interactions and metabolic abnormalities play a critical role in the GC progression.

scholarly journals Plasma proteomic profiles of healthy and mastitic cows – host responses to bovine mastitis

2013 ◽  
Vol 56 (1) ◽  
pp. 980-987 ◽  
Author(s):  
L.L. Niu ◽  
C.H. Wei ◽  
L.X. Du
Keyword(s):  
Dairy Cows ◽  
Acute Phase Proteins ◽  
Bovine Mastitis ◽  
Economic Loss ◽  
Differentially Expressed ◽  
Host Responses ◽  
Common Disease ◽  
Differentially Expressed Proteins ◽  
Proteomic Profiling ◽  
Two Dimensional Gel Electrophoresis

Abstract. Mastitis is the most common disease in dairy cows and has resulted in a tremendous economic loss in dairy industry. In the present study, differentially expressed proteins (DEP) were identified among healthy, moderate and severe mastitic cows by proteomic profiling. The health status of cows was closely determined by the somatic cell count (SCC). Differentially expressed proteins were resolved using the two-dimensional gel electrophoresis (2-DE) with the pH 4–7 non-linear DryStrips. Subsequently, 8 protein spots, which altered more than 3-fold, were isolated and identified with the matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI TOF/TOF MS). The identified spots were split into four proteins: α-2-HS-glycoprotein, serum albumin, transthyretin (TTR) and haptoglobin, respectively. Compared with the healthy cows, the expression of haptoglobin was up-regulated in mastitic cows, and the others were down-regulated. Moreover, the proteomic data were consistent with the results of Western blot. All of the identified DEPs were acute phase proteins, which acted together and represented the consequence of serial cascades after mastitic infection. More importantly, the α-2-HS-glycoprotein was novel identified corresponding to the bovine mastitis in Chinese Holstein dairy cows. Taken together, our results indicate that the host responses may play an important role in the pathogenesis of mastitis and provide the potential diagnostic indicator of the underlying mastitis in dairy cows.

scholarly journals Identification and Verification of the Main Differentially Expressed Proteins in Gastric Cancer via iTRAQ Combined with Liquid Chromatography-Mass Spectrometry

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Zhihua Gao ◽  
Jiabao Wang ◽  
Yuru Bai ◽  
Jun Bao ◽  
Erqing Dai
Keyword(s):  
Gastric Cancer ◽  
Western Blotting ◽  
Normal Mucosa ◽  
Gastric Cancer Tissue ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Exploratory Research ◽  
Differentially Expressed Proteins ◽  
Normal Tissues ◽  
Itraq Analysis

Background. To find the potential intersections between the differentially expressed proteins and abnormally expressed genes in gastric cancer (GC) patients. Methods. Gastric cancer tissue and adjacent normal mucosa tissue were used for iTRAQ analysis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) analysis were used to evaluate gene function. Western blotting and immunohistochemistry (IHC) were applied to verify the protein expression. Results. A total of 2770 proteins were identified, of which 147 proteins were upregulated and 159 proteins were downregulated. GO analysis revealed that the differentially expressed genes were mainly enriched for the terms “cellular process,” “binding,” and “cell.” The results of the KEGG analysis showed that the most abundantly enriched proteins were involved in the “focal adhesion” pathway. The results of the PPI analysis showed that VCAM1 was located at the center of the PPI network. Western blotting and IHC analysis demonstrated that VCAM1, FLNA, VASP, CAV1, PICK1, and COL4A2 were differentially expressed in GC and adjacent normal tissues, which was consistent with the results of the iTRAQ analysis. Conclusion. In conclusion, 6 highly differentially expressed proteins were identified as novel differentially expressed proteins in human GC. This exploratory research may provide useful information for the treatment of gastric cancer in the clinic.

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