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转录组测序鉴定 ANLN 为膀胱癌有前途的预后生物标志物。

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

机构信息

Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, P.R. China.

Department of Geriatrics, Changhai Hospital, Second Military Medical University, Shanghai, P.R. China.

出版信息

Sci Rep. 2017 Jun 9;7(1):3151. doi: 10.1038/s41598-017-02990-9.

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.

摘要

膀胱尿路上皮癌(BLCA)的预后差异很大,即使对于具有相似病理特征的患者也是如此。我们对十对 BLCA 样本和相邻正常组织进行了转录组测序,以鉴定差异表达的基因。与正常组织相比,肌动蛋白(ANLN)被鉴定为在 BLCA 样本中显著上调的转录本。使用 qRT-PCR 和免疫组织化学法分别在 40 例和 209 例患者中研究了候选基因的预后能力。表达水平升高的 ANLN 患者与较差的癌症特异性(中位,22.4 与 37.3 个月,p=0.001)、无进展(中位,19.7 与 27.9 个月,p=0.001)和无复发生存(中位,17.1 与 25.2 个月,p=0.011)相关。对 TCGA 和 NCBI-GEO 公共数据集进行了外部验证。使用小干扰 RNA 在 J82 和 5637 细胞中敲低 ANLN 显著抑制了细胞增殖、迁移和侵袭能力。此外,敲低 ANLN 导致 G2/M 期阻滞和细胞周期蛋白 B1 和 D1 的表达降低。微阵列分析表明,ANLN 在细胞迁移中起主要作用,并与几种癌症相关的信号通路密切相关。总之,ANLN 被鉴定为一种有前途的预后生物标志物,可用于分层 BLCA 的不同风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302d/5466664/396637523a45/41598_2017_2990_Fig1_HTML.jpg

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