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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

ABSTRACT: The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p?=?0.001), progression-free (median, 19.7 vs. 27.9 months, p?=?0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p?=?0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

SUBMITTER: Zeng S

PROVIDER: S-EPMC5466664 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

Zeng Shuxiong S Yu Xiaowen X Ma Chong C Song Ruixiang R Zhang Zhensheng Z Zi Xiaoyuan X Chen Xin X Wang Yang Y Yu Yongwei Y Zhao Junjie J Wei Rongchao R Sun Yinghao Y Xu Chuanliang C

Scientific reports 20170609 1

The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 pati ...[more]

PMID: 28600503

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Project description:Bladder cancer (BC) is the ninth most common malignancy worldwide. Bladder urothelial carcinoma (BLCA) constitutes more than 90% of bladder cancer (BC). The five-year survival rate is 5-70%, and patients with BLCA have a poor clinical outcome. The identification of novel clinical molecular markers in BLCA is still urgent to allow for predicting clinical outcomes. This study aimed to identify a novel signature integrating the three-dimension transcriptome of protein coding genes, long non-coding RNAs, microRNAs that is related to the overall survival of patients with BLCA, contributing to earlier prediction and effective treatment selection, as well as to the verification of the established model in the subtypes identified. Gene expression profiling and the clinical information of 400 patients diagnosed with BLCA were retrieved from The Cancer Genome Atlas (TCGA) database. A univariate Cox regression analysis, robust likelihood-based survival modelling analysis and random forests for survival regression and classification algorithms were used to identify the critical biomarkers. A multivariate Cox regression analysis was utilized to construct a risk score formula with a maximum area under the curve (AUC = 0.7669 in the training set). The significant signature could classify patients into high-risk and low-risk groups with significant differences in overall survival time. Similar results were confirmed in the test set (AUC = 0.645) and in the entire set (AUC = 0.710). The multivariate Cox regression analysis indicated that the five-RNA signature was an independent predictive factor for patients with BLCA. Non-negative matrix factorization and a similarity network fusion algorithm were applied for identifying three molecular subtypes. The signature could separate patients in every subtype into high- and low- groups with a distinct difference. Gene set variation analysis of protein-coding genes associated with the five prognostic RNAs demonstrated that the co-expressed protein-coding genes were involved in the pathways and biological process of tumourigenesis. The five-RNA signature could serve as to some degree a reliable independent signature for predicting outcome in patients with BLCA.

Project description:BackgroundTUBA1C is an α-tubulin isoform involved in mitosis, and its dysregulation has been implicated in tumor progression. There is still no clear understanding of its role in bladder urothelial carcinoma (BLCA).MethodsThis study examined the differential expression of TUBA1C and its prognostic significance in bladder cancer based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and also assessed the correlation of TUBA1C expression level with immune cell infiltration and immune checkpoint gene expression levels and the half-inhibitory concentration (IC50) of different chemotherapeutic agents. Immunotherapy response was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We detected TUBA1C expression in BLCA cells using PCR and Western blotting. Functional assays, including CCK-8, colony formation, transwell, apoptosis and cell cycle assays, were also performed to assess the oncogenic role of TUBA1C in BLCA.ResultIn three independent public cohorts, TUBA1C was significantly upregulated in bladder tumor tissues, and high TUBA1C expression in bladder cancer was associated with a poorer outcome than low expression. TUBA1C was an independent prognostic risk factor for bladder cancer, and numerous immune checkpoint genes and infiltrating immune cells were associated with TUBA1C. TIDE analysis revealed that TUBA1C showed great potential for predicting the immunotherapy response in bladder cancer patients. In addition, drug sensitivity analysis revealed that high TUBA1C expression indicated sensitivity to multiple chemotherapeutic agents. Functional assays revealed that silencing TUBA1C significantly inhibited the proliferation, migration and invasion of BLCA cells and induced apoptosis and cell cycle arrest.ConclusionThe overexpression of TUBA1C in bladder cancer predicts a poor prognosis and may also be a potential immunotherapeutic target. As a prognostic marker, TUBA1C influences tumor progression by regulating the cell cycle.

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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

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Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.

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