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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

Schematic representation of the strategy used to identify the differentially expressed proteins in GC tissues.
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Fig1: Schematic representation of the strategy used to identify the differentially expressed proteins in GC tissues.

Mentions: The experimental workflow of this study is shown in Figure 1. To discover plasma membrane protein alterations associated with GC, six pools of plasma membrane samples (three controls and three GC) were generated by pooling samples from 4 subjects for each pool. The purity of the plasma membrane after Percoll density gradient centrifugation was detected by western blot analysis. Figure 2 indicated that the plasma membrane was highly enriched in the marker, Na+/K+-ATPase, compared to the total lysis fraction. A total of 501 proteins were identified in the workflow (Additional file 1: Table S1). To further assess the efficacy of the protocol for the enrichment of plasma membrane proteins, the subcellular locations and functions were cataloged according to the gene ontology (GO) component annotations from literatures. Figure 3 showed that 175 proteins (about 35%) have been assigned as plasma membrane or membrane-associated proteins. Of the remaining proteins with subcellular annotation, approximately 16.9% of the identified proteins are extracellular, and 20.1% proteins locate in cytoplasm. 10% proteins locate in mitochondria and 11.5% proteins are nuclear or nuclear associated proteins. Other 6.5% proteins are mainly from cytoskeleton and endoplasmic reticulum.Figure 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)

Schematic representation of the strategy used to identify the differentially expressed proteins in GC tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Schematic representation of the strategy used to identify the differentially expressed proteins in GC tissues.
Mentions: The experimental workflow of this study is shown in Figure 1. To discover plasma membrane protein alterations associated with GC, six pools of plasma membrane samples (three controls and three GC) were generated by pooling samples from 4 subjects for each pool. The purity of the plasma membrane after Percoll density gradient centrifugation was detected by western blot analysis. Figure 2 indicated that the plasma membrane was highly enriched in the marker, Na+/K+-ATPase, compared to the total lysis fraction. A total of 501 proteins were identified in the workflow (Additional file 1: Table S1). To further assess the efficacy of the protocol for the enrichment of plasma membrane proteins, the subcellular locations and functions were cataloged according to the gene ontology (GO) component annotations from literatures. Figure 3 showed that 175 proteins (about 35%) have been assigned as plasma membrane or membrane-associated proteins. Of the remaining proteins with subcellular annotation, approximately 16.9% of the identified proteins are extracellular, and 20.1% proteins locate in cytoplasm. 10% proteins locate in mitochondria and 11.5% proteins are nuclear or nuclear associated proteins. Other 6.5% proteins are mainly from cytoskeleton and endoplasmic reticulum.Figure 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