A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome

Jonathan L. Robinson, Amir Feizi, Mathias Uhlén, Jens Nielsen*

*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.
Original languageEnglish
JournalCell Reports
Volume26
Issue number10
Pages (from-to)2622-2635
ISSN2211-1247
DOIs
Publication statusPublished - 2019

Keywords

  • cancer biomarkers
  • pan-cancer
  • protein secretion
  • secretome
  • systems biology
  • unfolded protein response

Cite this

Robinson, Jonathan L. ; Feizi, Amir ; Uhlén, Mathias ; Nielsen, Jens. / A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome. In: Cell Reports. 2019 ; Vol. 26, No. 10. pp. 2622-2635.
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abstract = "The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.",
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Robinson, JL, Feizi, A, Uhlén, M & Nielsen, J 2019, 'A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome', Cell Reports, vol. 26, no. 10, pp. 2622-2635. https://doi.org/10.1016/j.celrep.2019.02.025

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome. / Robinson, Jonathan L.; Feizi, Amir; Uhlén, Mathias; Nielsen, Jens.

In: Cell Reports, Vol. 26, No. 10, 2019, p. 2622-2635.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome

AU - Robinson, Jonathan L.

AU - Feizi, Amir

AU - Uhlén, Mathias

AU - Nielsen, Jens

PY - 2019

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N2 - The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.

AB - The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.

KW - cancer biomarkers

KW - pan-cancer

KW - protein secretion

KW - secretome

KW - systems biology

KW - unfolded protein response

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DO - 10.1016/j.celrep.2019.02.025

M3 - Journal article

VL - 26

SP - 2622

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JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

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Robinson JL, Feizi A, Uhlén M, Nielsen J. A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome. Cell Reports. 2019;26(10):2622-2635. https://doi.org/10.1016/j.celrep.2019.02.025

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