Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy

Sumit Sahni; Christopher Nahm; Christoph Krisp; Mark P. Molloy; Shreya Mehta; Sarah Maloney; Malinda Itchins; Nick Pavlakis; Stephen Clarke; David Chan; Anthony J. Gill; Viive M. Howell; Jaswinder Samra; Anubhav Mittal

doi:10.3389/fonc.2020.00237

Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy

Sumit Sahni, Christopher Nahm, Christoph Krisp, Mark P. Molloy, Shreya Mehta, Sarah Maloney, Malinda Itchins, Nick Pavlakis, Stephen Clarke, David Chan, Anthony J. Gill, Viive M. Howell, Jaswinder Samra, Anubhav Mittal^*

^*Corresponding author for this work

Australian Proteome Analysis Facility (APAF)

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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Abstract

Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.

Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders.

Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log₂ ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients.

Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.

Original language	English
Article number	237
Pages (from-to)	1-10
Number of pages	10
Journal	Frontiers in Oncology
Volume	10
DOIs	https://doi.org/10.3389/fonc.2020.00237
Publication status	Published - 4 Mar 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

pancreatic ductal adenocarcinoma
biomarkers
neoadjuvant chemotherapy
proteomics
SWATH-MS

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10.3389/fonc.2020.00237

Publisher version (open access)Final published version, 1.23 MBLicence: CC BY

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Sahni, S., Nahm, C., Krisp, C., Molloy, M. P., Mehta, S., Maloney, S., Itchins, M., Pavlakis, N., Clarke, S., Chan, D., Gill, A. J., Howell, V. M., Samra, J., & Mittal, A. (2020). Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy. Frontiers in Oncology, 10, 1-10. Article 237. https://doi.org/10.3389/fonc.2020.00237

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title = "Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy",

abstract = "Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.",

keywords = "pancreatic ductal adenocarcinoma, biomarkers, neoadjuvant chemotherapy, proteomics, SWATH-MS",

author = "Sumit Sahni and Christopher Nahm and Christoph Krisp and Molloy, {Mark P.} and Shreya Mehta and Sarah Maloney and Malinda Itchins and Nick Pavlakis and Stephen Clarke and David Chan and Gill, {Anthony J.} and Howell, {Viive M.} and Jaswinder Samra and Anubhav Mittal",

note = "Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2020",

month = mar,

day = "4",

doi = "10.3389/fonc.2020.00237",

language = "English",

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T1 - Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy

AU - Sahni, Sumit

AU - Nahm, Christopher

AU - Krisp, Christoph

AU - Molloy, Mark P.

AU - Mehta, Shreya

AU - Maloney, Sarah

AU - Itchins, Malinda

AU - Pavlakis, Nick

AU - Clarke, Stephen

AU - Chan, David

AU - Gill, Anthony J.

AU - Howell, Viive M.

AU - Samra, Jaswinder

AU - Mittal, Anubhav

N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/3/4

Y1 - 2020/3/4

N2 - Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.

AB - Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.

KW - pancreatic ductal adenocarcinoma

KW - biomarkers

KW - neoadjuvant chemotherapy

KW - proteomics

KW - SWATH-MS

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AN - SCOPUS:85082682845

SN - 2234-943X

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JO - Frontiers in Oncology

JF - Frontiers in Oncology

M1 - 237

ER -

Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy

Abstract

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