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
497P - Sintilimab in combination with anlotinib in advanced NSCLC treated with first-line PD-1 antibodies: An open, single-arm, phase II trial
Presenter: Ying Jin
Session: Poster Display
Resources:
Abstract
498P - Frailty-adjusted life expectancy and survival in older lung cancer patients: A large-scale electronic health-record based study
Presenter: Thao Tu
Session: Poster Display
Resources:
Abstract
499P - Long-term survival and treatment (tx) patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC): Japanese cohort of a global real-world (rw) observational study
Presenter: Daichi Fujimoto
Session: Poster Display
Resources:
Abstract
500P - The effectiveness and safety of durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small cell lung cancer: Real-world, multicenter, observational study (NEJ056)
Presenter: Hidehito Horinouchi
Session: Poster Display
Resources:
Abstract
501P - One-year survival outcomes of unresectable stage III non-small cell lung cancer patients who underwent PD-1 inhibitor plus chemo as induction therapy
Presenter: Xin Wang
Session: Poster Display
Resources:
Abstract
502P - Impact of sarcopenia on the outcome of patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy followed by durvalumab
Presenter: Kentaro Tamura
Session: Poster Display
Resources:
Abstract
503P - Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with locally advanced NSCLC
Presenter: TSUYOSHI HIRATA
Session: Poster Display
Resources:
Abstract
504P - Real-world outcomes with induction systemic therapy for stage III in eligible for upfront local therapy: Pre vs post immunotherapy era in a tertiary referral centre
Presenter: Praveen Kumar Marimuthu
Session: Poster Display
Resources:
Abstract
505P - Neoadjuvant PD-1 inhibitor (tislelizumab) plus platinum–etoposide in patients with limited-stage small cell lung cancer: A phase II trial
Presenter: Junjie Hu
Session: Poster Display
Resources:
Abstract
506P - Intrathoracic progression is still the most dominant failure pattern after first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: Implications for thoracic radiotherapy
Presenter: Byoung Hyuck Kim
Session: Poster Display
Resources:
Abstract