Abstract 452: TGF-β signaling pathway-related gene mutations are associated with increased neoantigen counts, enhanced cytolytic activity, and improved survival outcomes in TP53-mutated endometrial carcinoma

Abstract 452: TGF-β signaling pathway-related gene mutations are associated with increased neoantigen counts, enhanced cytolytic activity, and improved survival outcomes in TP53-mutated endometrial carcinoma

Abstract TP53-mutation is a poor prognostic marker for uterine corpus endometrial carcinoma (UCEC). TGF-β is known to promote tumor progression via immune suppression, particularly NK and T cell-mediated cytotoxicity, in the tumor microenvironment. We aimed to analyze the impact of TGF-β signaling p...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.452-452
Main Authors: Bae, William H., Hwang, Jin Young, Hur, Won Kyung, Nam, Myungwoo, Choi, Yoonhee, Kim, Leeseul, Lee, Yeun Ho, Cheng, William, Kim, Eugene, Yu, Emma, Jung, Chan Mi, Chuang, Jeff, Wang, Victor, Chae, Young Kwang
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Language:eng
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Summary:Abstract TP53-mutation is a poor prognostic marker for uterine corpus endometrial carcinoma (UCEC). TGF-β is known to promote tumor progression via immune suppression, particularly NK and T cell-mediated cytotoxicity, in the tumor microenvironment. We aimed to analyze the impact of TGF-β signaling pathway-related gene mutation on the immune landscape and survival outcomes in TP53-mutated UCEC patients. cBioPortal was queried to obtain the UCEC The Cancer Genome Atlas cohort data (TCGA, 529 patients). The neoantigen counts were predicted using the CloudNeo pipeline. Survival outcomes were compared in the TGF-β signaling pathway-related gene mutated group, which were defined as genetic variances in TGFBR1, TGFBR2, ACVR2A, ACVR1B, SMAD2, SMAD3, or SMAD4, and the TGF-β signaling pathway-related gene non-mutated group. The cytolytic activity score was defined as a geometric mean of mRNA expression of perforin and granzyme. The duration of overall survival and disease-free survival were also obtained from cBioPortal. Out of the 529 UCEC patients, 192(36.3%) cancer tissues with TP53 mutations were analyzed for this study. 44 patients (22.9%) had more than one mutation in their TGF-β signaling pathway-related genes. TGF-β signaling pathway-related gene mutated group, when compared to a non-mutated group, was associated with significantly increased neoantigen counts (519.3 vs. 20.34 ; p
ISSN:0008-5472
1538-7445