Abstract
Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR+ CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR- tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers.
| Original language | English |
|---|---|
| Pages (from-to) | 54-67 |
| Number of pages | 14 |
| Journal | Journal of Proteomics |
| Volume | 126 |
| DOIs | |
| Publication status | Published - 2015 Aug 3 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
Cite this
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Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis. / Sethi, Manveen K.; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S.; Packer, Nicolle H.; Paik, Young-Ki; Hancock, William S.; Fanayan, Susan.
In: Journal of Proteomics, Vol. 126, 03.08.2015, p. 54-67.Research output: Contribution to journal › Article
TY - JOUR
T1 - Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis
AU - Sethi, Manveen K.
AU - Thaysen-Andersen, Morten
AU - Kim, Hoguen
AU - Park, Cheol Keun
AU - Baker, Mark S.
AU - Packer, Nicolle H.
AU - Paik, Young-Ki
AU - Hancock, William S.
AU - Fanayan, Susan
PY - 2015/8/3
Y1 - 2015/8/3
N2 - Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR+ CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR- tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers.
AB - Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P<0.05, fold change>1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR+ CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR- tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers.
UR - http://www.scopus.com/inward/record.url?scp=84930965675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930965675&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2015.05.037
DO - 10.1016/j.jprot.2015.05.037
M3 - Article
C2 - 26054784
AN - SCOPUS:84930965675
VL - 126
SP - 54
EP - 67
JO - Journal of Proteomics
JF - Journal of Proteomics
SN - 1874-3919
ER -