A novel 20-gene prognostic score in pancreatic adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. In order to better prognosticate patients with PDAC, we identified 20 genes by utilizing publically available high-throughput transcriptomic data from GEO, TCGA and ICGC which are associated with overall survival and event-free survival. A score generated based on the expression matrix of these genes was validated in two independent cohorts. We find that this "Pancreatic cancer prognostic score 20-PPS20" is independent of the confounding factors in multivariate analyses, is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological subgroups but can predict response to targeted therapy as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

Development and validation of glycolysis‐related prognostic score for prediction of prognosis and chemosensitivity of pancreatic ductal adenocarcinoma

“…To better prognosticate patients with PDAC, researchers have established a 20‐gene score by utilizing publicly available high‐throughput transcriptomic data from GEO, TCGA and ICGC which have also reported on OS data. This 20‐gene pancreatic cancer prognostic score could define not only prognostic and biological subgroups, but predicted their responses to targeted therapy 33 . However, these risk scores did not focus on genes relating to glucose metabolism in PDAC, and the prediction efficiency was relatively low.…”

Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes

“…For comparison with our model, we selected two prognostic risk models: 20 gene signatures [ 21 ] and 36 gene signatures [ 24 ]. Survival analysis indicated that the PAAD prognosis of the high-risk score and low-risk score groups was different except for the 20-gene signature (Fig.…”

Development and validation of a four‐lipid metabolism gene signature for diagnosis of pancreatic cancer

“…The prognostic value of various gene expression profiles has been studied in pancreatic cancer over the past decade. For example, Demirkol Canlı S and collaborators identified a gene signature composed of 20 prognostic genes (PPS20), indicating overall survival and event-free survival of pancreatic cancer [39]. Wolfe AR et al developed a 4-miRNA molecular signature that is associated with risk of local-regional recurrence and overall survival after pancreatic cancer resection [40].…”

“…For example, Demirkol Canli et al . [ 39 ] identified a gene signature composed of 20 prognostic genes (PPS20), indicating OS and event‐free survival of pancreatic cancer. Wolfe et al .…”