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Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs

Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs
Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs
Background
Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasising. Proteomic analysis of cSCCs can provide insight into biological processes responsible for metastasis as well as future therapeutic targets and prognostic biomarkers.

Objectives
This study aimed to identify proteins associated with development of metastasis in cSCC.

Methods
A proteomic-based approach was employed on 105 completely-excised, primary cSCCs, comprising 52 which metastasised (P-M) and 53 which had not metastasised at 5 years post-surgery (P-NM). Formalin-fixed, paraffin-embedded cSCCs were microdissected and subjected to proteomic profiling after one dimensional (1D), and separately two dimensional (2D), liquid chromatography fractionation.

Results
A discovery set of 24 P-Ms and 24 P-NMs identified 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P-Ms and P-NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. Findings were verified by multiple reaction monitoring on 6 peptides from 2 proteins, Annexin A5 (ANXA5) and Dolichyl-diphosphooligosaccahride-protein glycosyltransferase non-catalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n=57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve (AUC) of 0.929 (CI=0.8277-1), an accuracy of 91.18% and higher sensitivity and specificity than cSCC staging systems currently in clinical use.

Conclusions
This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.
0007-0963
Shapanis, Andrew
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Lai, Chester
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Smith, Stephen
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Coltart, George
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Sommerlad, Matthew
26951faa-23a5-4266-8f38-66907bba9856
Schofield, James
529d3c88-857e-4431-93c2-e76577377ba7
Parkinson, Erika
b7294dcc-43d3-46c4-bd19-7f6795b80fe6
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Shapanis, Andrew
98b07884-92a9-4c00-afad-12194e339cbc
Lai, Chester
29ba48ea-2d38-497f-8cf9-400237f6a3a0
Smith, Stephen
013c6f3b-71ca-4bc1-b3cb-be1cb2970bce
Coltart, George
f260bc0e-2e4c-4eb6-944c-85e966e688a3
Sommerlad, Matthew
26951faa-23a5-4266-8f38-66907bba9856
Schofield, James
529d3c88-857e-4431-93c2-e76577377ba7
Parkinson, Erika
b7294dcc-43d3-46c4-bd19-7f6795b80fe6
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd

Shapanis, Andrew, Lai, Chester, Smith, Stephen, Coltart, George, Sommerlad, Matthew, Schofield, James, Parkinson, Erika, Skipp, Paul and Healy, Eugene (2020) Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs. British Journal of Dermatology. (doi:10.1111/bjd.19485).

Record type: Article

Abstract

Background
Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasising. Proteomic analysis of cSCCs can provide insight into biological processes responsible for metastasis as well as future therapeutic targets and prognostic biomarkers.

Objectives
This study aimed to identify proteins associated with development of metastasis in cSCC.

Methods
A proteomic-based approach was employed on 105 completely-excised, primary cSCCs, comprising 52 which metastasised (P-M) and 53 which had not metastasised at 5 years post-surgery (P-NM). Formalin-fixed, paraffin-embedded cSCCs were microdissected and subjected to proteomic profiling after one dimensional (1D), and separately two dimensional (2D), liquid chromatography fractionation.

Results
A discovery set of 24 P-Ms and 24 P-NMs identified 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P-Ms and P-NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. Findings were verified by multiple reaction monitoring on 6 peptides from 2 proteins, Annexin A5 (ANXA5) and Dolichyl-diphosphooligosaccahride-protein glycosyltransferase non-catalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n=57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve (AUC) of 0.929 (CI=0.8277-1), an accuracy of 91.18% and higher sensitivity and specificity than cSCC staging systems currently in clinical use.

Conclusions
This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.

Text
BJD Final accepted manuscript etc - Accepted Manuscript
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More information

Accepted/In Press date: 31 July 2020
e-pub ahead of print date: 13 August 2020
Published date: 24 September 2020

Identifiers

Local EPrints ID: 443403
URI: http://eprints.soton.ac.uk/id/eprint/443403
ISSN: 0007-0963
PURE UUID: d50187b9-247d-4f33-ae68-907fdc18a57e
ORCID for Andrew Shapanis: ORCID iD orcid.org/0000-0003-4147-6956
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959

Catalogue record

Date deposited: 24 Aug 2020 16:33
Last modified: 28 Oct 2021 04:01

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Contributors

Author: Andrew Shapanis ORCID iD
Author: Chester Lai
Author: Stephen Smith
Author: George Coltart
Author: Matthew Sommerlad
Author: James Schofield
Author: Erika Parkinson
Author: Paul Skipp ORCID iD
Author: Eugene Healy

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