Abstract 1427P
Background
Cancer/testis antigens (CTA) are cancer-specific, immunogenic tumor antigens that are potential targets for cancer immunotherapy. There is limited literature regarding their co-expression and prognostic role in gastroesophageal adenocarcinoma (GEAC). This study evaluated the CTA landscape of GEAC and their correlation with different clinicopathological parameters and survival.
Methods
RNA was extracted from 46 clinical GEAC FFPE tumors and processed for targeted RNA-seq. Biomarkers of tumor inflammation gene signature, cell proliferation signature, CD8, PD-L1 IHC were assessed. CTA (17 CTA genes) positivity was classified as gene expression rank ≥ 5. Kruskal-Wallis test was used to determine the association of CTA with all biomarkers. Pearson’s correlation was utilized to study CTA co-expression. To study the effect of CTA expression on survival, we used the Cox Regression model with potential covariates followed by pairwise posthoc analysis.
Results
In 46 GEAC samples (33 overweight defined by Body-Mass Index or BMI≥25;13 normal weight or BMI<25) from metastatic patients, we investigated CTA prevalence of 17 CTA genes which ranged from 4.35% to 65.2% positivity. Next, we scrutinized the CTA expression between the two BMI groups and found many CTA genes (BAGE, XAGE1B, GAGE13, and GAGE2A, NY-ESO-1 & LAGE-1A) showed higher expression in normal-weight samples. Expression of some CTA genes was inversely correlated with CD8 expression. Most importantly, we discovered a significant co-expression pattern of multiple CTA genes (4.205x10-6 ≥ p < 0.05). Finally, we performed a Cox Regression analysis to reveal a significant association of LAGE-1A (p=0.047) expression with worsened overall survival (OS) in all patients when accounted for known confounders. Interestingly, NY-ESO-1 expression was associated with improved progression-free survival (PFS)(p=0.034) and OS (p=0.024) in immune checkpoint inhibitor-treated patients (n=23).
Conclusions
We investigated the landscape of CTA in GEAC in the context of BMI. CTA expression was higher in normal-weight individuals. More importantly, we described a novel CTA co-expression landscape in GEAC and their potential prognostic association with OS and PFS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Mukherjee: Other, Personal and Institutional, Member of the Board of Directors, Unpaid: Esophageal Cancer Action Network. S. Pabla: Financial Interests, Personal, Stocks/Shares: Omniseq. J. Conroy: Financial Interests, Personal, Stocks/Shares: Omniseq. All other authors have declared no conflicts of interest.