Dataset Information

Inflammatory microenvironment in the initiation and progression of bladder cancer.

ABSTRACT: Accumulating evidence suggests the idea that chronic inflammation may play a critical role in various malignancies including bladder cancer and long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is significantly effective in reducing certain cancer incidence and mortality. However, the molecular mechanisms leading to malignant transformation and the progression of bladder cancer in a chronically inflammatory environment remain largely unknown. In this review, we will describe the role of inflammation in the formation and development of bladder cancer and summarize the possible molecular mechanisms by which chronic inflammation regulates cell immune response, proliferation and metastasis. Understanding the novel function orchestrating inflammation and bladder cancer will hopefully provide us insights into their future clinical significance in preventing bladder carcinogenesis and progression.

SUBMITTER: Sui X

PROVIDER: S-EPMC5696263 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Inflammatory microenvironment in the initiation and progression of bladder cancer.

Sui Xinbing X Lei Liming L Chen Liuxi L Xie Tian T Li Xue X

Oncotarget 20171006 54

Accumulating evidence suggests the idea that chronic inflammation may play a critical role in various malignancies including bladder cancer and long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is significantly effective in reducing certain cancer incidence and mortality. However, the molecular mechanisms leading to malignant transformation and the progression of bladder cancer in a chronically inflammatory environment remain largely unknown. In this review, we will describ ...[more]

PMID: 29190997

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Project description:BackgroundThe tumor microenvironment (TME) is not only a key factor in the malignant progression of cancer but also plays an indispensable role in tumor immunotherapy. As an important regulatory factor in the TME, long non-coding RNAs (incRNA) are important for the development of bladder cancer. The purpose of this study was to explore the molecular mechanism of malignant progression of bladder cancer (BCa) from the perspective of immunology, establish a reliable signature, and evaluate its effect on prognosis, metastasis, and the effectiveness of immunotherapy.MethodsThe TME was assessed by single-sample gene set enrichment analysis (ssGSEA) in 373 patients with muscle invasive bladder cancer (MIBC) in The Cancer Genome Atlas (TCGA). Combining RNA sequence data from 49 BCa patients in our center, we established TME-related prognostic signatures (TMERPS) based on TME-related immune prognosis genes using weighted gene correlation network analysis, selection operator Cox analysis, minimum absolute shrinkage, and survival analysis. Real-Time Quantitative PCR was used for expression level analysis of related genes. Functional enrichment analysis and nomograms were used to explore the potential impact of TMERPS on the immune system, prognosis, and metastasis.ResultsThe ssGSEA proved to be an accurate assessment of immune levels in BCa samples. TMERPS was established based on six TME-associated prognostic lncRNAs and was shown to be closely associated with prognosis, metastasis, and immune levels, and to have a significant stratifying effect on the therapeutic efficacy of immune checkpoint inhibitors. Finally, three TMERPS-based nomograms were shown to be effective in predicting prognosis, lymph node metastasis, and distant metastasis in BCa patients.ConclusionsTMERPS can stratify BCa patients into different risk groups with different prognoses, immunotherapy sensitivity, and risk of metastasis. TMERPS-based nomograms can effectively predict prognosis and metastasis in BCa patients.

Project description:ObjectiveThe malignant progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is common and has detrimental effect on patients. We aimed to elucidate the underlying mechanisms of the malignant progression from an immunological perspective and establish a reliable signature for prognostic prediction and immunotherapeutic strategies.MethodsThe Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm was applied to the GSE32894 data set to identify the different tumor-infiltrating immune cells involved in NMIBC and MIBC. Using weighted gene correlation network analysis, survival analysis and least absolute shrinkage and selection operator Cox analysis, we established an immune prognostic signature (IPS) based on 14 overall survival-associated immune genes in The Cancer Genome Atlas (TCGA). Functional enrichment analyses and nomogram were performed to explore the potential effects and prognostic performance of the IPS. Furthermore, the RNA-sequence data from our center were used to validate the expression levels of the selected immune genes in BLCA samples.ResultsDiverse proportions of macrophage subtypes were observed between NMIBC and MIBC. Patients with high risk scores had a worse prognosis than patients with low risk scores in training (TCGA) and validation data sets (GSE32894, GSE13507, and GSE48277). The IPS was a useful prognostic factor for patients treated with immunotherapy in the IMvigor210 trial. Hallmarks of multiple oncogenic pathways were significantly enriched in the high risk group. A novel nomogram model was established for prognostic predictions. The dysregulated expression of the selected immune genes between NMIBC and MIBC was also validated in BLCA samples.ConclusionDysregulation of the immune microenvironment promoted the malignant progression from NMIBC to MIBC. The IPS can stratify patients into different risk groups with distinct prognoses and immunotherapeutic susceptibility, thus facilitating personalized immunotherapy.

Dataset Information

Inflammatory microenvironment in the initiation and progression of bladder cancer.

Publications

Inflammatory microenvironment in the initiation and progression of bladder cancer.

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