Identification of EFEMP2 as a Serum Biomarker for the Early Detection of Colorectal Cancer with Lectin Affinity Capture Assisted Secretome Analysis of Cultured Fresh Tissues

Yao, Ling; Lao, Weifeng; Zhang, Yan; Tang, Xiaorong; Hu, Xueqiang; He, Chao; Hu, Xiaofang; Xu, Lisa X.

doi:10.1021/pr300020p

Cited by 48 publications

(49 citation statements)

References 70 publications

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“…In addition to these concordances with clinical gene expression data, our proteomics-based discovery pipeline identified other proteins that are potential serological biomarkers for colorectal cancer patients: a recent study by Yao and colleagues [28] identified EFEMP2 (EGF-containing fibulin-like extracellular matrix protein 2 or Fibulin 4) and thrombospondin 2 (THBS2) as a potential biomarkers detected in the serum of colorectal cancer patients. In accord with these data, we detected both EFEMP2 and THBS2 in both primary and secondary colon tumors but not in normal tissues.…”

Section: Resultsmentioning

confidence: 80%

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

et al. 2014

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BackgroundColorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States. Despite the fact that tumor cell-intrinsic mechanisms controlling colorectal carcinogenesis have been identified, novel prognostic and diagnostic tools as well as novel therapeutic strategies are still needed to monitor and target colon cancer progression. We and others have previously shown, using mouse models, that the extracellular matrix (ECM), a major component of the tumor microenvironment, is an important contributor to tumor progression. In order to identify candidate biomarkers, we sought to define ECM signatures of metastatic colorectal cancers and their metastases to the liver.MethodsWe have used enrichment of extracellular matrix (ECM) from human patient samples and proteomics to define the ECM composition of primary colon carcinomas and their metastases to liver in comparison with normal colon and liver samples.ResultsWe show that robust signatures of ECM proteins characteristic of each tissue, normal and malignant, can be defined using relatively small samples from small numbers of patients. Comparisons with gene expression data from larger cohorts of patients confirm the association of subsets of the proteins identified by proteomic analysis with tumor progression and metastasis.ConclusionsThe ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of colon tumors. The ECM proteins defined here represent candidate serological or tissue biomarkers and potential targets for imaging of occult metastases and residual or recurrent tumors and conceivably for therapies. Furthermore, the methods described here can be applied to other tumor types and can be used to investigate other questions such as the role of ECM in resistance to therapy.

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Section: Resultsmentioning

confidence: 80%

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

et al. 2014

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“…drugs, cytokines, radioisotopes) that could be coupled, for example, to anti-disease-specific ECM protein antibodies, on the model of systems developed in the Neri lab [80, 81]. In addition, proteolytic fragments of ECM proteins can be released in body fluids and could be used as readouts for disease progression or treatment efficiency [82–84]. …”

Section: Introductionmentioning

confidence: 99%

The extracellular matrix: Tools and insights for the “omics” era

et al. 2016

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The extracellular matrix (ECM) is a fundamental component of multicellular organisms that provides mechanical and chemical cues that orchestrate cellular and tissue organization and functions. Degradation, hyperproduction or alteration of the composition of the ECM cause or accompany numerous pathologies. Thus, a better characterization of ECM composition, metabolism, and biology can lead to the identification of novel prognostic and diagnostic markers and therapeutic opportunities. The development over the last few years of high-throughput (“omics”) approaches has considerably accelerated the pace of discovery in life sciences. In this review, we describe new bioinformatic tools and experimental strategies for ECM research, and illustrate how these tools and approaches can be exploited to provide novel insights in our understanding of ECM biology. We also introduce a web platform “the matrisome project” and the database MatrisomeDB that compiles in silico and in vivo data on the matrisome, defined as the ensemble of genes encoding ECM and ECM-associated proteins. Finally, we present a first draft of an ECM atlas built by compiling proteomics data on the ECM composition of 14 different tissues and tumor types.

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“…CRC biomarkers can be detected through a differential proteomic analysis of blood. Serum biomarkers have been described and used for non-invasive testing to detect CRC [14,15]. Potential biomarkers have also been identified by evaluating CRC cell line-derived secretome [16].…”

Section: Introductionmentioning

confidence: 99%

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker of colorectal cancer

Xiao

Shao

et al. 2016

Front. Med.

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Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. We aimed to find novel molecules as potential biomarkers for the early diagnosis of CRC. A serum-free conditioned medium was successfully collected from three pairs of CRC tissue and adjacent normal tissue. iTRAQ-based quantitative proteomic analysis was applied to compare the differences in secretome between primary CRC mucosa and adjacent normal mucosa. A total of 145 kinds of proteins were identified. Of these proteins, 29 were significantly different between CRC and normal tissue. Tropomyosin 2 β (TPM2) exhibited the most significant differences; as such, this protein was selected for further validation. Quantitative real-time PCR indicated that the mRNA expression of TPM2 significantly decreased in the CRC tissue compared with the paired adjacent normal tissue. Immunohistochemical analysis also confirmed that TPM2 was barely detected at protein levels in the CRC tissue. In summary, this study revealed potential molecules for future biomarker applications and provided an efficient approach for the differential analysis of cancer-associated secretome. TPM2 may be valuable for the early diagnosis of CRC.

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Identification of EFEMP2 as a Serum Biomarker for the Early Detection of Colorectal Cancer with Lectin Affinity Capture Assisted Secretome Analysis of Cultured Fresh Tissues

Cited by 48 publications

References 70 publications

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

The extracellular matrix: Tools and insights for the “omics” era

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker of colorectal cancer

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