TY - JOUR
T1 - C-reactive protein is a prognostic biomarker in pancreatic ductal adenocarcinoma patients
AU - Bonazzi, Vanessa F.
AU - Aoude, Lauren G.
AU - Brosda, Sandra
AU - Bradford, Julia J.
AU - Lonie, James M.
AU - Loffler, Kelly A.
AU - Gartside, Michael G.
AU - Patel, Kalpana
AU - Mukhopadhyay, Pamela
AU - Keane, Colm
AU - Gebski, Val J.
AU - Kench, James G.
AU - Goldstein, David
AU - Waddell, Nicola
AU - Barbour, Andrew P.
AU - the Australasian Gastro-Intestinal Trials Group (AGITG) GAP investigators
PY - 2025/2
Y1 - 2025/2
N2 - Aim: The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes. The non-randomized Phase II study “Gemcitabine and Abraxane for resectable Pancreatic cancer” (GAP) demonstrated the feasibility of perioperative gemcitabine/abraxane. Long-term survival in PDAC requires an effective immune response; hence, we undertook this translational study of the GAP trial cohort to identify immune-oncology biomarkers for clinical use. Methods: We combined Nanostring nCounter technology with immunohistochemistry to investigate the correlation between gene expression and overall patient survival. Findings were investigated in samples from the International Cancer Genome Consortium (ICGC, n = 88) and the Australian Pancreatic Genome Initiative (APGI, n = 227). Results: We confirmed that human equilibrative nucleoside transporter 1 (hENT1) expression was not a prognostic marker in PDAC but patients with high levels of hENT1 were more likely to live longer than 24 months post-surgery. Additionally, CD274 (PD-L1) and two novel biomarkers of survival, cathepsin W (CTSW) and C-reactive protein (CRP), were identified in the GAP cohort (n = 19). CRP expression was confirmed in data from the ICGC. Although PD-L1 and CTSW proteins were not significant across all three cohorts, results show that low CRP mRNA and protein expression are associated with longer overall survival in all three patient groups. Conclusion: PDAC patients with long survival have higher hENT1 expression levels. Furthermore, CRP expression is a biomarker of poor prognosis following perioperative chemotherapy and resection in PDAC patients and thus may be useful for identifying patients who could benefit from more aggressive adjuvant strategies.
AB - Aim: The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes. The non-randomized Phase II study “Gemcitabine and Abraxane for resectable Pancreatic cancer” (GAP) demonstrated the feasibility of perioperative gemcitabine/abraxane. Long-term survival in PDAC requires an effective immune response; hence, we undertook this translational study of the GAP trial cohort to identify immune-oncology biomarkers for clinical use. Methods: We combined Nanostring nCounter technology with immunohistochemistry to investigate the correlation between gene expression and overall patient survival. Findings were investigated in samples from the International Cancer Genome Consortium (ICGC, n = 88) and the Australian Pancreatic Genome Initiative (APGI, n = 227). Results: We confirmed that human equilibrative nucleoside transporter 1 (hENT1) expression was not a prognostic marker in PDAC but patients with high levels of hENT1 were more likely to live longer than 24 months post-surgery. Additionally, CD274 (PD-L1) and two novel biomarkers of survival, cathepsin W (CTSW) and C-reactive protein (CRP), were identified in the GAP cohort (n = 19). CRP expression was confirmed in data from the ICGC. Although PD-L1 and CTSW proteins were not significant across all three cohorts, results show that low CRP mRNA and protein expression are associated with longer overall survival in all three patient groups. Conclusion: PDAC patients with long survival have higher hENT1 expression levels. Furthermore, CRP expression is a biomarker of poor prognosis following perioperative chemotherapy and resection in PDAC patients and thus may be useful for identifying patients who could benefit from more aggressive adjuvant strategies.
KW - biomarker
KW - C-reactive protein
KW - pancreatic adenocarcinoma
UR - http://www.scopus.com/inward/record.url?scp=85164526295&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1026563
UR - http://purl.org/au-research/grants/NHMRC/1109048
U2 - 10.1111/ajco.13993
DO - 10.1111/ajco.13993
M3 - Article
AN - SCOPUS:85164526295
SN - 1743-7555
VL - 21
SP - 77
EP - 86
JO - Asia-Pacific Journal of Clinical Oncology
JF - Asia-Pacific Journal of Clinical Oncology
IS - 1
ER -
