Abstract LB261: GPR171, a prognostic marker of improved survival in cervix cancer: A Deep South Consortium in Oncology (DSCO) Project

Abstract Background: Recent evidence shows that G-protein-coupled receptor-171 (GPR171) may be an important T-cell checkpoint in tumor immunity. The role of GPR171 in cervical cancer has not been studied. Here, we sought to investigate the association of GPR171 with other tumor immune markers and DNA damage in cervical cancer and its impact on patient survival. Methods: 3,371 samples were sequenced for RNA (NovaSeq, WTS) (Caris Life Sciences, Phoenix, AZ). GPR171, CD274, CD96 and TIGIT were stratified by top 25% (-H) and bottom 75% (-L). T-cell inflamed gene expression profile (GEP) signature was calculated by Ayers 2017. Real-world overall survival (rwOS) information was obtained from insurance claims and calculated from tissue collection or first cycle of pembrolizumab to last contact for molecularly defined cohorts. DNA damage was evaluated by repair-assisted damage-detection assay (RADD). Hazard ratio (HR) was calculated by Cox proportional hazards model and p-values were calculated by log-rank test. Results: GPR171-H was associated with longer rwOS compared to GPR171-L (+9.3 mo, HR=0.73, CI 0.652 - 0.819; p<0.001). This was independent of histological subtype as well as HPV status. GPR171 expression was positively correlated with markers of tumor immunity PD-L1, CD96, TIGIT expression and T-cell inflamed GEP. High expression of GPR171, TIGIT and CD96 showed improved rwOS and post-pembrolizumab survival (+18.9-mo, HR: 0.56, CI 0.478 - 0.651; p<0.001; +7.2-mo, HR: 0.683, CI 0.518 - 0.901; p=0.007). High expression of all targets also correlated with the presence of high DNA damage. Conclusions: GPR171-H was associated with improved survival, increased expression of markers of tumor immunity and DNA damage. Our data elucidates its potential role in immune cell infiltration and inflammation within the tumor microenvironment. This study shows the potential of GPR171 as a novel prognostic marker for survival in cervical cancer. Citation Format: Tanvi Joshi, Elisabeth Murphy, Sagar Chokshi, Kevin J. Lee, Sharon Wu, Joanne Xiu, Matthew J. Oberley, Britt K. Erickson, Charles A. Leath, Symmes Johnson, Bunja Rungruang, Rodney P. Rocconi, Nathaniel Jones, Jennifer Scalici. GPR171, a prognostic marker of improved survival in cervix cancer: A Deep South Consortium in Oncology (DSCO) Project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB261.