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IL-6 expression regulates tumorigenicity and correlates with prognosis in bladder cancer.

ABSTRACT: Identification of potential tumor markers will help stratify and identify a tumor's malignant potential and its response to specific therapies. IL-6 has been reported to be a predictor in various cancers. Therefore, the present study was performed to highlight the role of IL-6 in improving treatment and determining prognosis of bladder cancer. The human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments, in which biological changes after experimental manipulation of IL-6 were explored, including tumor behavior and related signaling in bladder cancer. In addition, clinical specimens from 85 patients with muscle-invasive, and 50 with non-muscle invasive bladder cancers were selected for immunohistochemical staining to evaluate the predictive capacity of IL-6 in relation to clinical outcome. The data revealed that IL-6 was overexpressed in the bladder cancer specimens compared with non-malignant tissues at both mRNA and protein levels. Positive staining of IL-6 was significantly correlated with higher clinical stage, higher recurrence rate after curative treatment, and reduced survival rate. Tumor growth and invasive capability were attenuated when IL-6 was blocked. The underlying changes included decreased cell proliferation, less epithelial-mesenchymal transition (EMT), decreased DNA methyltransferase 1 expression and attenuated angiogenesis. In conclusion, our findings showed that IL-6 could be a significant predictor for clinical stage and prognosis of bladder cancer. Moreover, targeting IL-6 may be a promising strategy for treating bladder cancer.

SUBMITTER: Chen MF

PROVIDER: S-EPMC3640078 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Expression of interleukin-23 receptor (IL-23R) and IL-17 in urinary bladder carcinoma (UBC) was investigated to explore the correlations with prognosis. IL-23/IL-17 axis significantly inhibited the development of inflammatory bowel disease. Thirty patients with UBC were enrolled in Zhengzhou Central Hospital Affiliated to Zhengzhou University from September 2013 to September 2014. Tumor tissue and adjacent healthy tissue were collected, and the levels of IL-23R and IL-17 mRNA were detected by RT-PCR. Thirty healthy people were also selected to serve as normal control group. Serum levels of IL-23R and IL-17 in serum of UBC patients and normal controls were detected by ELISA, and the correlations with clinical features of UBC were analyzed. Pearson's correlation analysis was used to analyze the correlation between IL-23R and IL-17 protein expression. Follow-up study was performed by phone or during patient's visit to out-patient department. Overall survival (OS) and disease-free survival (DFS) curves were plotted by Kaplan-Meier method to analyze the correlation between expression of IL-23R and IL-17 and survival time. ROC curve was used to detect the diagnostic values of IL-23R and IL-17 protein for UBC. Levels of IL-23R and IL-17 mRNA in UBC tissue were 3.26 and 2.65 times higher than those in adjacent tissue (P<0.05), and serum levels of IL-23R and IL-17 protein in UBC patients were significantly higher than those in normal control group. Protein expression levels of IL-23R and IL-17 were correlated with clinical stage and lymph node metastasis in UBC patients (P<0.05), and Cox hazard model showed that L-23R and IL-17 expression may be independent factors for UBC (P<0.05), and high expression levels of IL-23R and IL-17 significantly shortened the OS and DFS (P<0.05). Serum levels of IL-23R and IL-17 can be used to effectively diagnose clinical stage and lymph node metastasis of UBC patients, and the combined diagnosis has a higher sensitivity and specificity than the diagnosis using a single factor. These findings indicated that expression levels of IL-23R and IL-17 were increased in tumor tissue and serum of UBC patients, and the increased expression levels of IL-23R and IL-17 were correlated with poor prognosis. Detection of IL-23R and IL-17 levels has certain clinical significance in the diagnosis and prognosis of UBC.

Project description:BackgroundIGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown.MethodsWe aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes.ResultsPan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage.ConclusionIGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

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IL-6 expression regulates tumorigenicity and correlates with prognosis in bladder cancer.

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