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Identification of secretory gelsolin as a plasma biomarker associated with distant organ metastasis of colorectal cancer

Journal of Molecular Medicine volume 90, pages 187–200 (2012)Cite this article

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. More than half of all CRC patients will develop metastases, which represents the major cause of death for CRC patients. CRC metastases confined in other organs are potentially resectable, and patients who receive curative resections appear to have better outcomes. Thus, the early detection of metastasis in CRC patients could improve their survival rate after curative surgery. Here, we report the use of Cy-dye labeling combined with multi-dimensional fractionation and mass spectrometry as a proteomics-based approach for identifying CRC metastasis-associated biomarker(s) in plasma samples collected from three CRC patients upon diagnosis of their primary and metastatic tumors. Among the eight identified proteins, we used Western blot analysis and an in-house-developed ELISA to validate the increased plasma levels of one, secretory (plasma) gelsolin, in >80% of CRC patients with distal metastases in a larger sample cohort (32 patients). We also found a significant increase of secretory gelsolin in plasma samples of stage IV versus stages I–III CRC patients before treatment. Furthermore, immunohistochemistry showed that secretory gelsolin was highly overexpressed in CRC tissue specimens compared to adjacent normal tissues, and a cell model study showed that secretory gelsolin may help regulate CRC cell migration.

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Acknowledgments

This work was supported by grants from the National Science Council of Taiwan, Republic of China (NSC96-2320-B-182-031-MY3 and 99-2923-B-182-002-MY2), the Ministry of Education, Taiwan, Republic of China (EMRPD190041), and Chang Gung University and Memorial Hospital, Taiwan, Republic of China (CMRPD160099 and CMRPD180033).

Disclosures/Conflicts of interest

None.

Author information

Affiliations

  1. Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Ming-Hung Tsai, Pei-Hua Peng, Jeng-Ting Chen, Shin-Jie Lin, Ling-Ling Hsieh & Jau-Song Yu

  2. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Chih-Ching Wu, Ying Liang, Kun-Yi Chien & Jau-Song Yu

  3. Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Chih-Ching Wu

  4. Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Yung-Chin Hsiao, Kun-Yi Chien & Jau-Song Yu

  5. Department of Public Health, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Ling-Ling Hsieh

  6. Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China

    Rei-Ping Tang

  7. Department of Cell and Molecular Biology, Chang Gung University, Taoyuan, Taiwan, Republic of China

    Jau-Song Yu

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  1. Ming-Hung Tsai
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  2. Chih-Ching Wu
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Correspondence to Ling-Ling Hsieh or Jau-Song Yu.

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Supporting information 1

One supplementary materials and methods file, four supplementary table files, and five supplementary figure files that support the presented data. Table S1. Clinicopathological characteristics of the 32 paired CRC plasma samples used in this study. Table S2. Comparative analysis of fluorescence intensity of the Cy-dye-labeled plasma proteins after multi-dimensional separation. Table S3. Summary of the secretory gelsolin levels determined by Western blot analysis and ELISA in the 32 paired CRC plasma samples used in this study. Table S4. Relationship between secretory gelsolin expression levels and clinicopathologic characteristics of the 148 CRC patients. Figure S1. Fractionation, visualization, and quantitative analysis of the Cy-dye labeled plasma proteins. Figure S2. Representative fluorimetric images of the protein bands containing each protein identified in experiments 1 and 2. Figure S3. Representative peptide mass fingerprints and matched peptides (from MALDI-TOF MS) and the MS/MS spectra of the two selected peptides (from MicrOTOF-Q MS) used for protein identification. Figure S4. Protein staining patterns of the 32 paired plasma samples. Figure S5. Establishment of a sandwich ELISA for secretory gelsolin. (PDF 1,538 kb)

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Tsai, MH., Wu, CC., Peng, PH. et al. Identification of secretory gelsolin as a plasma biomarker associated with distant organ metastasis of colorectal cancer. J Mol Med 90, 187–200 (2012). https://doi.org/10.1007/s00109-011-0817-4

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  • DOI: https://doi.org/10.1007/s00109-011-0817-4

Keywords

  • Colorectal cancer
  • Metastasis
  • Secretory gelsolin
  • Plasma biomarker
  • Migration