Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy
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Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy. / Sahni, Sumit; Nahm, Christopher; Krisp, Christoph; Molloy, Mark P; Mehta, Shreya; Maloney, Sarah; Itchins, Malinda; Pavlakis, Nick; Clarke, Stephen; Chan, David; Gill, Anthony J; Howell, Viive M; Samra, Jaswinder; Mittal, Anubhav.
In: FRONT ONCOL, Vol. 10, 2020, p. 237.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
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 © 2020 Sahni, Nahm, Krisp, Molloy, Mehta, Maloney, Itchins, Pavlakis, Clarke, Chan, Gill, Howell, Samra and Mittal.
PY - 2020
Y1 - 2020
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.
U2 - 10.3389/fonc.2020.00237
DO - 10.3389/fonc.2020.00237
M3 - SCORING: Journal article
C2 - 32195182
VL - 10
SP - 237
JO - FRONT ONCOL
JF - FRONT ONCOL
SN - 2234-943X
ER -