Abstract 249P
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.
Resources from the same session
571P - Dacomitinib in treatment-naïve EGFR-mutant NSCLC patients with multiple brain metastases: Initial efficacy and safety data from a phase II study
Presenter: Yongfeng Yu
Session: Poster Display
Resources:
Abstract
572P - Multivariable five-year survival prediction model for prognosing patients with EGFR-mutated NSCLC treated with EGFR-TKIs
Presenter: Qi-An Wang
Session: Poster Display
Resources:
Abstract
573P - LUMINATE-103: Real-world treatment patterns and outcomes of patients (pts) with epidermal growth factor receptor mutant (EGFR MU), non-squamous (NSQ) locally advanced/metastatic non-small cell lung cancer (a/mNSCLC): Pooled analysis of large US electronic health record (EHR) datasets
Presenter: Byoung Chul Cho
Session: Poster Display
Resources:
Abstract
574P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutations
Presenter: Lin Wu
Session: Poster Display
Resources:
Abstract
575P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC and brain metastasis: A multicenter cohort study
Presenter: Puyuan Xing
Session: Poster Display
Resources:
Abstract
576P - Clonality of both EGFR and co-occurring TP53 mutations affect the treatment efficacy of the third-generation EGFR-TKIs in advanced-stage EGFR-mutant non-small cell lung cancer
Presenter: Wen Feng Fang
Session: Poster Display
Resources:
Abstract
577P - A study of the efficacy and safety of amivantamab in EGFR exon 20 insertion (E20I) mutations in NSCLC
Presenter: Daeho Choi
Session: Poster Display
Resources:
Abstract
578P - Tyrosine kinase inhibitor treatment of elderly patients with epidermal growth factor receptor mutated advanced non-small cell lung cancer: A multi-institute retrospective study
Presenter: Ling-Jen Hung
Session: Poster Display
Resources:
Abstract
579P - Real-world study of dacomitinib as first-line treatment for patients with EGFR-mutant non-small cell lung cancer
Presenter: Ji Eun Shin
Session: Poster Display
Resources:
Abstract
580P - Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor <italic>(EGFR)</italic> 21L858R mutation: A multicenter, ambispective, consecutive case-series study
Presenter: Shouzheng Wang
Session: Poster Display
Resources:
Abstract