A Novel HOXA10-Associated 5-Gene–Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma

Abstract

Purpose: Despite the significant association of molecular subtypes with poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients, little effort has been made to identify the underlying pathway(s) responsible for this prognosis. Identifying a clinically relevant prognosis-based gene signature may be the key to improving patient outcomes. Experimental Design: We analyzed the transcriptomic profiles of treatment-naïve surgically resected short- and long-term survivor tumors (GSE62452) for expression and survival, followed by validation in several datasets. These results were corroborated by immunohistochemical analysis of PDAC-resected short- and long-term survivor tumors. The mechanism of this differential survival was investigated using CIBERSORT and pathway analyses. Results: We identified a short-surviving prognostic subtype of PDAC with a high degree of significance (p=0.018). One hundred thirty genes in this novel subtype were found to be regulated by a master regulator, HOXA10, and a five-gene signature derived from these genes, including BANF1, EIF4G1, MRPS10, PDIA4, and TYMS, exhibited differential expression in short-term survivors (STS) and a strong association with poor survival. This signature was further associated with the proportion of T-cells and macrophages found in STS and long-term survivors (LTS), demonstrating a potential role in PDAC immunosuppression. Pathway analyses corroborated these findings, revealing that this HOXA10-driven signature is associated with immune suppression and enhanced tumorigenesis. Conclusions: Overall, these findings reveal the presence of a HOXA10-associated prognostic subtype that can be used to differentiate between STS and LTS patients of PDAC and inform on the molecular interactions that play a role in this poor prognosis.

Identification of BANF1 as a novel prognostic biomarker in gastric cancer and validation via in-vitro and in-vivo experiments

“…Mao et al [ 12 ] showed that inhibition of BANF1 in cervical cancer inhibited the proliferation, migration, and invasion of cervical cancer cells, and Ren et al [ 24 ] showed that inhibition of BANF1 inhibited the proliferation and migration of esophageal cancer cells. Recent clinical studies have shown that BANF1 expression is elevated in patients with pancreatic cancer and short survival times [ 25 ]. There are very few studies on the mechanism of action of BANF1 in cancer, and most of the studies have only included expression- and cellular-level studies.…”