scholarly journals EP300 mutation is associated with tumor mutation burden and promotes antitumor immunity in bladder cancer patients

Aging ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 2132-2141 ◽  
Author(s):  
Gongmin Zhu ◽  
Lijiao Pei ◽  
Yuan Li ◽  
Xin Gou
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Antitumor Immunity ◽  
Tumor Mutation Burden ◽  
Mutation Burden

scholarly journals Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients

Aging ◽  
2021 ◽  
Author(s):  
Linglong Peng ◽  
Yang Li ◽  
Haitao Gu ◽  
Ling Xiang ◽  
Yongfu Xiong ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Antitumor Immunity ◽  
Tumor Mutation Burden ◽  
Mutation Burden

RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16528-e16528
Author(s):  
Liping Li ◽  
Mengmei Yang ◽  
Mengli Huang
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Negative Regulator ◽  
Wilcoxon Test ◽  
Wild Type ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Impact

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.

scholarly journals Network based analysis identifies TP53m-BRCA1/2wt-homologous recombination proficient (HRP) population with enhanced susceptibility to Vigil immunotherapy

2021 ◽  
Author(s):  
Elyssa Sliheet ◽  
Molly Robinson ◽  
Susan Morand ◽  
Khalil Choucair ◽  
David Willoughby ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Interaction Network ◽  
Analysis Data ◽  
Polymorphism Analysis ◽  
Relapse Free Survival ◽  
Double Blind ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Mutation Burden

AbstractThus far immunotherapy has had limited impact on ovarian cancer. Vigil (a novel DNA-based multifunctional immune-therapeutic) has shown clinical benefit to prolong relapse-free survival (RFS) and overall survival (OS) in the BRCA wild type and HRP populations. We further analyzed molecular signals related to sensitivity of Vigil treatment. Tissue from patients enrolled in the randomized double-blind trial of Vigil vs. placebo as maintenance in frontline management of advanced resectable ovarian cancer underwent DNA polymorphism analysis. Data was generated from a 981 gene panel to determine the tumor mutation burden and classify variants using Ingenuity Variant Analysis software (Qiagen) or NIH ClinVar. Only variants classified as pathogenic or likely pathogenic were included. STRING application (version 1.5.1) was used to create a protein-protein interaction network. Topological distance and probability of co-mutation were used to calculated the C-score and cumulative C-score (cumC-score). Kaplan–Meier analysis was used to determine the relationship between gene pairs with a high cumC-score and clinical parameters. Improved relapse free survival in Vigil treated patients was found for the TP53m-BRCAwt-HRP group compared to placebo (21.1 months versus 5.6 months p = 0.0013). Analysis of tumor mutation burden did not reveal statistical benefit in patients receiving Vigil versus placebo. Results suggest a subset of ovarian cancer patients with enhanced susceptibility to Vigil immunotherapy. The hypothesis-generating data presented invites a validation study of Vigil in target identified populations, and supports clinical consideration of STRING-generated network application to biomarker characterization with other cancer patients targeted with Vigil.

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