Effect of NCOR1 Mutations on Immune Microenvironment and Efficacy of Immune Checkpoint Inhibitors in Patient with Bladder Cancer

Lin, Anqi; Qiu, Zhengang; Zhang, Jian; Luo, Peng

doi:10.3389/fimmu.2021.630773

Cited by 30 publications

(29 citation statements)

References 54 publications

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“…Zhang et al identi ed NTRK3 as a potential prognostic biomarker associated with tumor mutation burden and immune in ltration in BLCA [17]. Lin et al found the effect of NCOR1 mutations on immune microenvironment and e cacy of ICB in patient with BLCA [42]. In this study, we predicted the immune checkpoints of FLG wild-type patients of different types, and the results showed that Sub2 patients respond is worse to immune checkpoint.…”

Section: Discussionmentioning

confidence: 71%

Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

Liang

Xiong

Chen

et al. 2021

Preprint

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Background Bladder cancer (BLCA) is one of most common urinary tract malignant tumor and immunotherapy have generated a great deal of interest in BLCA. Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of BLCA. Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Objective In this study, we aimed to investigate the role of mutations genes and subtypes in prognosis and immune checkpoint prediction in BLCA. Method Mutation information and expression profiles were acquired from The Cancer Genome Atlas (TCGA) database. Integrated bioinformatics analysis was carried out to explore the mutation genes of BLCA. Functional enrichment analysis Gene Ontology (GO) and Gene set enrichment analysis (GSEA) was conducted. The infiltrating immune cells and the prediction of ICB between different subtypes group were explored using immuCellAI algorithm. Results The mutation genes Filaggrin (FLG) gene were identified. Following the study on its subtypes and functional enrichment analysis, Sub2 of FLG-wide type was found to have relationships with poor prognosis and immune infiltration BLCA. What’s more, Sub2 of FLG-wide type may be used as a biomarker to predict the prognosis of BLCA patients receiving ICB. Conclusion This research provides a new basis and ideas for guiding the clinical application of BLCA immunotherapy.

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Section: Discussionmentioning

confidence: 71%

Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

Liang

Xiong

Chen

et al. 2021

Preprint

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“…The above results suggest that CTTNB1-MUT can be used as a biomarker for patients with HCC undergoing immunotherapy, and can help clinicians to more accurately distinguish responders from non-responders. An immunoinflammatory TIME is helpful in improving patients response to immunotherapy (11,14,35). In our study, T cells, B cells, M1-type macrophages and DCs were significantly enriched in the TIME of CTNNB1-WT HCC patients.…”

Section: Discussionmentioning

confidence: 99%

“…To avoid unnecessary toxicity, alternative treatments are recommended for patients who are not expected to respond to immunotherapy (8,9). Existing biomarkers include PD-L1 expression, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), and cytokines (8)(9)(10)(11)(12)(13)(14). The classification of PD-L1 in HCC is complex, and the level of spatial and cellular heterogeneity is high, which may affect the reliability and repeatability of PD-L1 as a predictor of response to treatment with ICIs in comparison to other markers (15).…”

Section: Introductionmentioning

confidence: 99%

CTNNB1 Alternation Is a Potential Biomarker for Immunotherapy Prognosis in Patients With Hepatocellular Carcinoma

et al. 2021

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BackgroundThe emergence of immune checkpoint inhibitors (ICIs) marks the beginning of a new era of immunotherapy for hepatocellular carcinoma (HCC), however, not all patients respond successfully to this treatment. A major challenge for HCC immunotherapy is the development of ways to screen for those patients that would benefit from this type of treatment and determine the optimal treatment plan for individual patients. Therefore, it is important to find a biomarker which allows for the stratification of HCC patients, which distinguishes responders from non-responders, thereby further improving the clinical benefits for those undergoing immunotherapy.MethodsWe used univariate and multivariate Cox risk proportional regression models to evaluate the relationship between non-synonymous mutations with a mutation frequency greater than 10%. We made a prognosis of an immunotherapy HCC cohort using mutation and prognosis data. An additional three HCC queues from the cbioportal webtool were used for further verification. The CIBERSORT, IPS, quanTIseq, and MCPcounter algorithms were used to evaluate the immune cells. PCA and z-score algorithm were used to calculate immune-related signature with published gene sets. Gene set enrichment analysis (GSEA) was used to compare the differences in the pathway-based enrichment scores of candidate genes between mutant and wild types.ResultsUnivariate and multivariate Cox results showed that only CTNNB1-Mutant(CTNNB1-MUT) was associated with progression-free survival (PFS) of HCC patients in the immunotherapy cohort. After excluding the potential bias introduced by other clinical features, it was found that CTNNB1-MUT served as an independent predictor of the prognosis of HCC patients after immunotherapy (P < 0.05; HR > 1). The results of the tumor immune microenvironment (TIME) analysis showed that patients with CTNNB1-MUT had significantly reduced activated immune cells [such as T cells, B cells, M1-type macrophages, and dendritic cells (DCs)], significantly increased M2-type macrophages, a significantly decreased expression of immunostimulating molecules, low activity of the immune activation pathways (cytokine pathway, immune cell activation and recruitment) and highly active immune depletion pathways (fatty acid metabolism, cholesterol metabolism, and Wnt pathway).ConclusionsIn this study, we found CTNNB1-MUT to be a potential biomarker for HCC immunotherapy patients, because it identified those patients are less likely to benefit from ICIs.

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“…Along with immunogenicity, studies have shown that inflammatory TIME can also increase patients' response to immunotherapy (33)(34)(35). Reports suggest that CD4+ and CD8+ TILs highly enriched in the tumor are related to a higher response rate after receiving immunotherapy (36,37).…”

Section: Discussionmentioning

confidence: 99%

Effect of TTN Mutations on Immune Microenvironment and Efficacy of Immunotherapy in Lung Adenocarcinoma Patients

Wang

Lin

et al. 2021

Front. Oncol.

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Immune checkpoint inhibitors (ICIs) effectively treat lung adenocarcinoma (LUAD) with fewer side effects. However, for LUAD patients, the lack of predictive markers for ICIs makes their clinical benefits less than ideal. Despite reports suggesting that a TTN (titin) mutation plays an important role in immunotherapy of solid tumors and gastric cancer, the relationship between the TTN mutation and LUAD immunotherapy has not been determined. We collected a LUAD cohort with whole-exome sequencing (WES) and immunotherapy prognosis. The ICI cohort was used to explore the relationship between TTN mutation status and prognosis. Then, the Cancer Genome Atlas (TCGA)-LUAD and Chen-LUAD cohorts were downloaded from the cbioportal website. We also used CIBERSORT, gene-set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA) to evaluate the proportion of immune cells and the degree of pathway activation in LUAD patients, respectively. DDR signaling pathways obtained from the Molecular Signatures Database (MSigDB), tumor mutation burden (TMB), and NAL were used to evaluate the immunogenicity of LUAD patients. In the ICI cohort, TTN-mutant (TTN-MT) had significantly longer overall survival (OS) than TTN-wildtype (TTN-WT) (P = 0.009). Univariate and multivariate COX models showed that TTN mutation status can independently predict immunotherapy prognosis. Notably, the results of tumor immune microenvironment (TIME) analysis showed that TTN-MT patients had inflammatory TIME, which showed enriched activated immune cells and higher immune scores. Immunogenicity analysis showed higher immunogenicity in TTN-MT patients, which indicated high levels of gene mutations in TMB, NAL, and DDR pathways. GSEA and ssGSEA results showed that TTN-MT was substantially enriched in chemokine secretion, inflammatory factor secretion, and antigen presentation. Some pathways related to immunosuppression and immune depletion were significantly downregulated. TTN-MT is associated with significantly prolonged OS in LUAD patients. Additionally, TTN-MT is related to high immunogenicity and inflammatory TIME, suggesting that TTN-MT may be a potential predictive marker for patients with LUAD to accept ICIs.

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Effect of NCOR1 Mutations on Immune Microenvironment and Efficacy of Immune Checkpoint Inhibitors in Patient with Bladder Cancer

Cited by 30 publications

References 54 publications

Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

Identification of a FLG-wide-type bladder cancer subtype with poor prognosis and prediction use in immune checkpoint

CTNNB1 Alternation Is a Potential Biomarker for Immunotherapy Prognosis in Patients With Hepatocellular Carcinoma

Effect of TTN Mutations on Immune Microenvironment and Efficacy of Immunotherapy in Lung Adenocarcinoma Patients

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