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

doi:10.1016/j.jprot.2015.05.037

Cited by 35 publications

(25 citation statements)

References 91 publications

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“…Proteomic studies of CRC have been conducted using surgically resected tissues to develop biomarkers and identify drug targets2627. However, the reliable quantification of the changes in tumor proteome and the interpretation of a large proteomic data set remain challenging.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Hao

Zhi

Wang

et al. 2017

Sci Rep

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The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Hao

Zhi

Wang

et al. 2017

Sci Rep

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“…Fisher's exact test was used to account for the sample pairing using the protein analysis program Scaffold Q+ version 4.4.3. A fold-change cut-off of 1.5 and a P-value cut-off of 0.05, as used by various quantitative proteomic studies (19)(20)(21)(22), were used as minimum criteria for differential protein expression. The construction of the interaction pathways between the differentially-expressed proteins was generated by Integrated System Interactome (24).…”

Section: Analysis Of Dius By Nano-lc-quadrupole-time-of-flight (Nlc-qmentioning

confidence: 99%

Proteomic profile of saliva and plasma from women with impalpable breast lesions

et al. 2016

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Abstract. The present study evaluated the proteomic profile of saliva and plasma from women with impalpable breast lesions using nano-liquid chromatography-quadrupole-time-of-flight (nLC-Q-TOF) technology. Plasma and saliva from patients with fibroadenoma (n=10), infiltrating ductal carcinoma (n=10) and healthy control groups (n=8) were assessed by combinations of inter/intra-group analyses, revealing significant quantitative and qualitative differences. The major differentially-expressed proteins in the saliva of patients compared with the controls were α2-macroglobulin and ceruloplasmin, but the proteins that met the minimum fold-change and P-value cut-offs were leukocyte elastase inhibitor and α-enolase, and deleted in malignant brain tumors 1. Concerning plasma, α-2-macroglobulin and ceruplasmin were upregulated, while other proteins such as haptoglobin, hemopexin and vitamin D-binding protein were downregulated compared with the control. The changes in immune, molecular transport and signaling pathways were the most representative in the proteomic profile of the saliva and plasma. This is the first study to describe the proteome of saliva and plasma from the same women with impalpable breast lesions.

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“…For example, Di Palma et al [43] applied FACS analysis to sort a limited number of colon stem cells extracted from mouse intestine which led to the identification of 1085 proteins. A recent proteomic analysis [46] of paired colorectal cancer and adjacent normal tissues from CRC patients identified 948 proteins in total, of which 184 proteins were differentially expressed (P<0.05, fold change >1.5) between tumor and non-tumor tissues. Among these proteins, cancer associated proteins such as FN1, TNC, DEFA1 and ITGB2 were found upregulated [46].…”

Section: Resultsmentioning

confidence: 99%

“…A recent proteomic analysis [46] of paired colorectal cancer and adjacent normal tissues from CRC patients identified 948 proteins in total, of which 184 proteins were differentially expressed (P<0.05, fold change >1.5) between tumor and non-tumor tissues. Among these proteins, cancer associated proteins such as FN1, TNC, DEFA1 and ITGB2 were found upregulated [46]. Using a proteomic analysis of minute amounts of colonic biopsies by enteroscopy sampling, Liu et al identified 2620 proteins between cancer mucosa and adjacent normal colorectal mucosa, of which 195 proteins were differentially upregulated in cancer tissues [47].…”

Section: Resultsmentioning

confidence: 99%

Protein Markers Associated with an ALDH Sub-Population in Colorectal Cancer

Yang¹,

Liu²,

Thakolwiboon³

et al. 2016

Journal of Proteomics & Bioinformatics

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ALDH has been shown to be a marker that denotes a sub-population of cancer stem cells in colorectal and other cancers. This sub-population of cells shows an increased risk for tumor initiation, metastasis, and resistance to chemotherapy and radiation resulting in recurrence and death. It is thus essential to identify the important signaling pathways related to ALDH1+ CSCs in colon cancer. The essential issue becomes to isolate pure sub-populations of cells from heterogeneous tissues for further analysis. To achieve this goal, tissues from colorectal cancer Stage III patients were immuno-stained with ALDH1 antibody. Target ALDH1+ and ALDH1− cells from the same tissue were micro-dissected using Laser Capture Microdissection (LCM). Captured cells were lysed and analyzed using LC-MS/MS where around 20,000 cells were available for analysis. This analysis resulted in 134 proteins which were differentially expressed between ALDH1+ and ALDH1− cells in three patient sample pairs. Based on these differentially expressed proteins an IPA pathway analysis was performed that showed two key pathways in cell to cell signaling and organismal injury and abnormalities. The IPA analysis revealed β-catenin, NFκB (p65) and TGFβ1 as important cancer-related proteins in these pathways. A TMA validation using immunofluorescence staining of tissue micro-arrays including 170 cases was used to verify that these key proteins were highly overexpressed in ALDH1+ cells in colon cancer tissues compared to ALDH1− cells.

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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

Cited by 35 publications

References 91 publications

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Proteomic profile of saliva and plasma from women with impalpable breast lesions

Protein Markers Associated with an ALDH Sub-Population in Colorectal Cancer

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