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Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer.

Gao W, Xu J, Wang F, Zhang L, Peng R, Shu Y, Wu J, Tang Q, Zhu Y - BMC Cancer (2015)

Bottom Line: Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins.Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples.Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 GuangZhou Road, Nanjing, 210029, China. Yoghurt831030@126.Com.

ABSTRACT

Background: Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets.

Methods: In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues.

Results: Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues.

Conclusions: A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis.

No MeSH data available.


Related in: MedlinePlus

Mass spectra of four representative proteins. (A) sigma non-opioid intracellular receptor 1, (B) flotillin 1, (C) CD 36 and (D) CD9.
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Fig4: Mass spectra of four representative proteins. (A) sigma non-opioid intracellular receptor 1, (B) flotillin 1, (C) CD 36 and (D) CD9.

Mentions: Proteins were labeled with TMT reagents and analyzed using tandem mass spectrometry to screen for the differentially expressed proteins between GC and adjacent normal tissues. To increase the coverage of protein identifications and the confidence of the data generated, three pools of adjacent normal tissues were labeled with TMT reagents 126, 127 and 128 respectively; pools of GC tissues were labeled with TMT reagents 129, 130 and 131 respectively. The relative quantification analysis by Maxquant 1.2.2.5 software comes with statistical analysis, however, most methods are prone to technical variation, so we included an additional 1.5-fold cut off for all TMT ratios to add stringency when classifying proteins as up- or down-regulated. A total of 205 differentially expressed proteins proteins were identified with 95% confidence (Additional file 2: Table S2). Of these, 82 plasma membrane proteins were found to have >1.5-fold difference in expression between the GC and adjacent normal tissues (Table 1). 24 proteins were downregulated in gastric cancer, whereas 58 were overexpressed compared to adjacent normal tissues. The plasma membrane/plasma membrane -associated proteins comprised about 40% of the total proteins detected. The mass spectra of four representative proteins (sigma non-opioid intracellular receptor 1, flotillin 1, CD36 and CD9 molecule) were shown in Figure 4.Table 1


Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer.

Gao W, Xu J, Wang F, Zhang L, Peng R, Shu Y, Wu J, Tang Q, Zhu Y - BMC Cancer (2015)

Mass spectra of four representative proteins. (A) sigma non-opioid intracellular receptor 1, (B) flotillin 1, (C) CD 36 and (D) CD9.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4525731&req=5

Fig4: Mass spectra of four representative proteins. (A) sigma non-opioid intracellular receptor 1, (B) flotillin 1, (C) CD 36 and (D) CD9.
Mentions: Proteins were labeled with TMT reagents and analyzed using tandem mass spectrometry to screen for the differentially expressed proteins between GC and adjacent normal tissues. To increase the coverage of protein identifications and the confidence of the data generated, three pools of adjacent normal tissues were labeled with TMT reagents 126, 127 and 128 respectively; pools of GC tissues were labeled with TMT reagents 129, 130 and 131 respectively. The relative quantification analysis by Maxquant 1.2.2.5 software comes with statistical analysis, however, most methods are prone to technical variation, so we included an additional 1.5-fold cut off for all TMT ratios to add stringency when classifying proteins as up- or down-regulated. A total of 205 differentially expressed proteins proteins were identified with 95% confidence (Additional file 2: Table S2). Of these, 82 plasma membrane proteins were found to have >1.5-fold difference in expression between the GC and adjacent normal tissues (Table 1). 24 proteins were downregulated in gastric cancer, whereas 58 were overexpressed compared to adjacent normal tissues. The plasma membrane/plasma membrane -associated proteins comprised about 40% of the total proteins detected. The mass spectra of four representative proteins (sigma non-opioid intracellular receptor 1, flotillin 1, CD36 and CD9 molecule) were shown in Figure 4.Table 1

Bottom Line: Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins.Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples.Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 GuangZhou Road, Nanjing, 210029, China. Yoghurt831030@126.Com.

ABSTRACT

Background: Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets.

Methods: In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues.

Results: Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues.

Conclusions: A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis.

No MeSH data available.


Related in: MedlinePlus