249P - The prognostic utility of Progestogen associated Endometrial protein (PAEP) gene expression in clear cell renal cell carcinoma (ccRCC)

Background

PAEP encodes for pregnancy-associated endometrial alpha-2 globulin; a glycoprotein with a wide spectrum of biological actions. One of which is related to immune system modulation. In this work, we evaluated the prognostic potential of PAEP in ccRCC and its impact on tumor immune microenvironment (TIME).

Methods

The ccRCC cohort of the cancer genome atlas program (TCGA) was accessed to obtain relevant clinicopathological parameters alongside PAEP mRNA expression data. Multivariate Cox logistic regression analysis was applied to evaluate the prognostic independency of PAEP expression in predicting the overall survival (OS). Gene set enrichment analysis (GSEA) algorithm was implemented to discern the molecular mechanisms affected by PAEP upregulation. TIME was assessed by predicting the immune suppressive cells infiltration and T-cell dysfunction using TIMER 2.0 and TIDE, respectively.

Results

The Kaplan-Meier estimate showed that high expression of PAEP is associated with shortened OS (HR: 2.511, 95% CI: 1.864-3.384, P < .0001). Multivariate Cox logistic regression analysis depicts PAEP expression as an independent prognostic variable (HR: 1.849, 95% CI: 1.304-2.621, P = .001). GSEA (H1: Hallmarks of cancer gene sets) identified the following pathways to be involved in the poor prognostic signature of PAEP: epithelial-mesenchymal transition, G2M checkpoint, E2F targets, IL6/JAK/STAT3 signaling, coagulation, complement, KRAS downregulation, and inflammatory response. TIME showed a significant infiltration of several immunosuppressive cellular elements including regulatory T cells (ρ = 0.256, P < .0001), cancer-associated fibroblasts (ρ = 0.194, P < .0001), and myeloid-derived suppressor cells (ρ = 0.194, P < .0001). PAEP was not associated with a significant T-cell dysfunction (continuous z score = −0.787, P = .431).

Conclusions

PAPE is being identified as potential prognostic biomarker in ccRCC that impact TIEM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.