Exploring the Pathological Mechanism of Bladder Cancer Based on Tumor Mutational Burden Analysis

Ma, Yao; Feng, Xiaofei; Yang, Wan-Xia; You, Chongge

doi:10.1155/2019/1093815

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Immune checkpoint molecule inhibitors have opened the possibility of immunotherapy for bladder cancer, especially for muscle-invasive and metastatic bladder cancer [24,25]. Recent research has correlated bladder cancer and the immune environment [26]. However, there are no available biomarkers to assess the effectiveness of immunotherapy in bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer

Zhu

et al. 2020

Bioscience Reports

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Background: Bladder cancer is the ninth most-common cancer worldwide and it is associated with high morbidity and mortality. Tumor mutational burden (TMB) is an emerging biomarker in cancer characterized by microsatellite instability. TMB has been described as a powerful predictor of tumor behavior and response to immunotherapy. Methods: A total of 443 bladder cancer samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for mutation types, TMB values, and prognostic value of TMB. Differentially expressed genes (DEGs) were identified from the TMB groupings. Functional analysis was performed to assess the prognostic value of the first 30 core genes. CIBERSORT algorithm was used to determine the correlation between the immune cells and TMB subtypes. Results: Single nucleotide polymorphism (SNP) and C>T were reported as the most common missense mutations and we also identified a high rate of mutations in TP53, TTN, KMT2D. Bladder cancer patients with high TMB showed a better prognosis. Enrichment analysis of the DEGs revealed that they were involved in the regulation of the P13K-Akt signaling pathway, cytokine–cytokine receptor interaction, and Ras signaling pathway. The high expression of hub genes ADRA2A, CXCL12, S1PR1, ADAMTS9, F13A1, and SPON1 was correlated with poor overall survival. Besides, significant differences in the composition of the immune cells of T cells CD8, T cells CD4 memory activated, NK cells resting and Mast cells resting were observed. Conclusions: The present study provides a comprehensive and systematic analysis of the prediction of TMB in bladder cancer and its clinical significance. Also, the study provides additional prognostic information and opportunities for immunotherapy in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer

Zhu

et al. 2020

Bioscience Reports

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“…Neoantigens are associated with tumor mutational burden (TMB) 17 ; patients with higher TMB can potentially form more neoantigens, thereby promoting anti‐tumor immune responses 18 . TMB has been used to predict the efficacy of immune checkpoint inhibitors (ICIs) in various cancers, including TNBC 19–24 . In addition, previous studies have demonstrated that combination of TMB and immune gene expression profile (GEP) could further distinguish responders from non‐responders in TNBC patients treated with ICIs 25 .…”

Section: Introductionmentioning

confidence: 99%

Integrated tumor genomic and immune microenvironment analysis identifies predictive biomarkers associated with the efficacy of neoadjuvant therapy for triple‐negative breast cancer

et al. 2022

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Background: Although neoadjuvant chemotherapy (NAC) is currently the best therapy for triple-negative breast cancer (TNBC), resistance still occurs in a considerable proportion of TNBC patients, making it crucial to understand resistance mechanisms and identify predictive biomarkers for patient selection.Methods: Biopsy samples were collected from 21 patients with TNBC who underwent NAC. Whole-exome sequencing, targeted sequencing, and multiplex immunohistochemistry (mIHC) were carried out on the all clinical samples and used to identify and validate potential biomarkers associated with response to NAC.In addition, data on 190 TNBC patients who had undergone chemotherapy were obtained from The Cancer Genome Atlas (TCGA) and analyzed to further validate our ndings.Results: Both the tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were signi cantly higher in responders than in non-responders. Higher response rates and longer survival rates were observed in patients with higher TMB. Patients with higher ratios of CD8 to M2 macrophages had higher response rates and improved survival rates. Finally, integrated analysis demonstrated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages could further distinguish responders from non-responders in both enrolled patients and from public data.Conclusions: The ndings of this study indicated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages may be a potential biomarker for improving the recognition of NAT responders, thereby providing a basis for developing precision NAT regimens.

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“…The somatic mutation accumulation promotes the formation of neoantigens which activate the immunogenicity of T cells to kill cancer cells. The cancers with high TMB often generate new antigens to recruit the immune cells ( 35 ). Consistent with the previous studies, our results showed that higher TMB tends to predict worse survival.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer

Li¹,

Wu²,

Fan³

et al. 2022

Ann Transl Med

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Background: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLCA) remains poorly described. Methods:We downloaded the transcriptome sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and lasso Cox regression analyses were performed to construct the prognostic risk signature, the predictive accuracy of which was validated in the subsequent independence and stratification analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the underlying molecular mechanisms involved in the signature to explore therapeutic vulnerabilities and potential targets in BLCA. Tumor mutational burden (TMB) and tumor immune dysfunction and exclusion (TIDE) were used to estimate the response to immune checkpoint inhibitors (ICIs). We further explored the potential new drug-target candidates based on the half maximal inhibitory concentration for this patient population.Results: Fifteen cuproptosis-related lncRNAs significantly associated with survival were identified to construct the risk signature based on the normalized expression level and regression coefficient of each gene.The patients with BLCA and high-risk scores defined by the signature were associated with worse survival outcomes. The differentially expressed genes (DEGs) between the 2 risk groups had different biological activity. Furthermore, the patients in the low-risk group exhibited a higher TMB index and a lower TIDE score. The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score.Conclusions: Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population.

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Exploring the Pathological Mechanism of Bladder Cancer Based on Tumor Mutational Burden Analysis

Cited by 11 publications

References 52 publications

Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer

Mining TCGA database for tumor mutation burden and their clinical significance in bladder cancer

Integrated tumor genomic and immune microenvironment analysis identifies predictive biomarkers associated with the efficacy of neoadjuvant therapy for triple‐negative breast cancer

Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer

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