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

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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Comparison of iodine contents in gastric cancer and surrounding normal tissues

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.101 ◽

2005 ◽

Vol 43 (6) ◽

Cited By ~ 7

Author(s):

Mine Gulaboglu ◽

Leyla Yildiz ◽

Fehmi Celebi ◽

Mustafa Gul ◽

Kemal Peker

Keyword(s):

Gastric Cancer ◽

Iodine Deficiency ◽

Normal Tissue ◽

Gastric Cancer Tissue ◽

Cancer Tissue ◽

Cancer Prevalence ◽

Normal Tissues ◽

The North ◽

Significant Difference ◽

North Eastern

AbstractIt has been suggested that iodine plays an important role in gastric cancer. Gastric cancer ranks first among the cancers in the north-eastern Anatolia region, Turkey, where iodine deficiency is common. In this study, iodine levels were determined in gastric cancer and surrounding normal tissues in 19 patients with gastric cancer. Tissue iodine levels were determined by the Foss method based on the Sandell-Kolt-hoff reaction. Tissue iodine levels were lower in gastric cancer tissue (17.8±3.4ngI/mg protein, mean±SEM) compared with surrounding normal tissue (41.7±8.0ngI/mg protein) (p<0.001). There was positive correlation between the iodine levels in gastric cancer tissue and surrounding normal tissue (r=0.845, p<0.001). There was no significant difference in iodine levels in cancer and surrounding normal tissue between male and female subjects. The iodine deficiency in our region may be one of the factors for increased gastric cancer prevalence. Our results support the hypothesis that iodine plays an important role in gastric cancer development.

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Differential Expression of Mimecan and Thioredoxin Domain–Containing Protein 5 in Colorectal Adenoma and Cancer: A Proteomic Study

Experimental Biology and Medicine ◽

10.3181/0701-rm-8 ◽

2007 ◽

Vol 232 (9) ◽

pp. 1152-1159 ◽

Cited By ~ 57

Author(s):

Yinghong Wang ◽

Yu Ma ◽

Bingjian Lü ◽

Enping Xu ◽

Qiong Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Adenoma ◽

Normal Mucosa ◽

Colorectal Adenomas ◽

Differentially Expressed ◽

Cancer Tissue ◽

Differentially Expressed Proteins ◽

Two Dimensional Gel Electrophoresis ◽

Proteomic Study ◽

Cancer Tissues

Adenoma is the major precursor lesion of colorectal cancer, one of the most common cancers worldwide. The elucidation of the molecular mechanism underlying adenoma is essential for early detection, prevention, and intervention of colorectal cancer. Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 27 differentially expressed proteins in adenoma, compared with matched normal mucosa and cancer tissue. Seventeen proteins were upregulated and six downregulated in adenoma when compared with the same proteins in individual-matched normal mucosa. Four were downregulated, but none upregulated in adenoma when compared with the same proteins in matched cancer tissue. Two novel proteins, mimecan and thioredoxin domain–containing protein 5 (TXNDC5), were further validated by Western blot in 8 colorectal adenomas and 19 cancers that were matched with normal mucosa. All adenoma and cancer tissues did not express mimecan, but all normal mucosa did ( P < 0.01). In contrast, TXNDC5 was significantly upregulated in colorectal adenoma and cancer tissues as compared with that in normal mucosa ( P < 0.05). This study clearly demonstrated that absence of mimecan and upregulation of TXNDC5 are involved in the early development of colorectal cancer. Thus, the differentially expressed proteins might serve as potential biomarkers for colorectal cancer detection and intervention.

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Identification of genes universally differentially expressed in gastric cancer

10.21203/rs.2.16787/v1 ◽

2019 ◽

Author(s):

Haidan Yan ◽

Yidan Shi ◽

Jiahui Zhang ◽

Haifeng Chen ◽

Qingzhou Guan ◽

...

Keyword(s):

Gastric Cancer ◽

Mapk Signaling ◽

Differentially Expressed ◽

Cancer Tissue ◽

Special Importance ◽

Cancer Genes ◽

Down Regulation ◽

Individual Level ◽

Normal Tissues ◽

Direct Neighbor

Abstract Background Due to the remarkable heterogeneity of gastric cancer (GC), differentially expressed genes (DEGs) identified at the population-level by case-control comparison cannot afford dysregulation frequency of each DEG in GC. Methods Firstly, the individual-level DEGs were identified for 1,090 GC tissues without paired normal tissues by the RankComp method. Secondly, we directly compared the gene expression in a cancer tissue with its paired normal tissue to identify individual-level DEGs for 448 paired cancer-normal gastric tissues. Results We found 25 DEGs dysregulated not only in more than 90% of 1,090 GC tissues, but also in more than 90% of 448 GC tissues with paired normal tissues. The 25 genes were defined as universal DEGs for GC which were further validated in our additionally measured 24 paired cancer-normal gastric tissues. Among the universal DEGs, four up-regulation genes ( BGN , E2F3 , PLAU and SPP1 ) and one down-regulation gene ( UBL3 ) were found to be cancer genes documented in the COSMIC or F-Census database. By analyzing protein-protein interaction network, we found 12 universal up-regulation genes and their 284 direct neighbor genes were significantly enriched with cancer genes and key biological pathways related to cancer, such as MAPK signaling pathway, Cell cycle and Focal adhesion. The 13 universal down-regulation genes and 16 direct neighbor genes were also significantly enriched with cancer genes and gastric acid secretion related pathway. Conclusion These universal DEGs may be of special importance for GC diagnosis and treatment targets, and can help to study the molecular mechanism of GC.

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Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey

BMC Genomics ◽

10.1186/s12864-019-6089-z ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Hao Wang ◽

Xiaoqi Zhu ◽

Junyan Shen ◽

En-Feng Zhao ◽

Dajun He ◽

...

Keyword(s):

Western Blotting ◽

Inflammatory Responses ◽

Circulatory System ◽

Absolute Quantification ◽

Fold Change ◽

Differentially Expressed ◽

Behavioral Experiment ◽

Receptor Interaction ◽

Differentially Expressed Proteins ◽

Itraq Analysis

Abstract Background The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein. Results Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice. Conclusions This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.

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Identification of Genes Universally Differentially Expressed in Gastric Cancer

BioMed Research International ◽

10.1155/2021/7326853 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yidan Shi ◽

Lishuang Qi ◽

Haifeng Chen ◽

Jiahui Zhang ◽

Qingzhou Guan ◽

...

Keyword(s):

Gastric Cancer ◽

Mapk Signaling ◽

Differentially Expressed ◽

Cancer Tissue ◽

Special Importance ◽

Cancer Genes ◽

Individual Level ◽

Normal Tissues ◽

Direct Neighbor ◽

Upregulated Genes

Owing to the remarkable heterogeneity of gastric cancer (GC), population-level differentially expressed genes (DEGs) identified using case-control comparison cannot indicate the dysregulated frequency of each DEG in GC. In this work, first, the individual-level DEGs were identified for 1,090 GC tissues without paired normal tissues using the RankComp method. Second, we directly compared the gene expression in a cancer tissue to that in paired normal tissue to identify individual-level DEGs among 448 paired cancer-normal gastric tissues. We found 25 DEGs to be dysregulated in more than 90% of 1,090 GC tissues and also in more than 90% of 448 GC tissues with paired normal tissues. The 25 genes were defined as universal DEGs for GC. Then, we measured 24 paired cancer-normal gastric tissues by RNA-seq to validate them further. Among the universal DEGs, 4 upregulated genes (BGN, E2F3, PLAU, and SPP1) and 1 downregulated gene (UBL3) were found to be cancer genes already documented in the COSMIC or F-Census databases. By analyzing protein-protein interaction networks, we found 12 universally upregulated genes, and we found that their 284 direct neighbor genes were significantly enriched with cancer genes and key biological pathways related to cancer, such as the MAPK signaling pathway, cell cycle, and focal adhesion. The 13 universally downregulated genes and 16 direct neighbor genes were also significantly enriched with cancer genes and pathways related to gastric acid secretion. These universal DEGs may be of special importance to GC diagnosis and treatment targets, and they may make it easier to study the molecular mechanisms underlying GC.

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PVT1 and ZFAS1 lncRNAs expressions and their biomarker value in gastric cancer tissue sampling among Iranian population

Molecular Biology Reports ◽

10.1007/s11033-021-06709-y ◽

2021 ◽

Author(s):

Narges Dastmalchi ◽

Samaneh Tayefeh-Gholami ◽

Ali Rajabi ◽

Reza Safaralizadeh

Keyword(s):

Gastric Cancer ◽

Gastric Cancer Tissue ◽

Iranian Population ◽

Cancer Tissue ◽

Tissue Sampling

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Expression and Content of Protein LC3B in Gastric Cancer Tissue, Relationship with Expression of mTOR, AMPK in Gastric Cancer Tissue and HER2 and PD-L1 Status of the Tumor

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-021-05376-0 ◽

2021 ◽

Author(s):

L. V. Spirina ◽

A. V. Avgustinovich ◽

S. G. Afanas’ev ◽

M. Yu. Volkov ◽

I. V. Kondakova

Keyword(s):

Gastric Cancer ◽

Gastric Cancer Tissue ◽

Cancer Tissue

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ELISA study of matrix metalloproteinases 2, 7, 9 and their type 2 tissue inhibitor in the tumors of gastric cancer patients: clinical and pathologic correlations

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2018-46-4-323-329 ◽

2018 ◽

Vol 46 (4) ◽

pp. 323-329

Author(s):

E. S. Gershtein ◽

A. A. Ivannikov ◽

V. L. Chang ◽

N. A. Ognerubov ◽

М. M. Davydov ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Matrix Metalloproteinases ◽

Tumor Progression ◽

Cancer Patients ◽

Univariate Analysis ◽

Gastric Cancer Tissue ◽

Cancer Tissue ◽

Gastric Cancer Patients

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.

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