Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.
Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma.
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转录组测序将 ANLN 确定为膀胱尿路上皮癌有前景的预后生物标志物
DOI：
10.1038/s41598-017-02990-9
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发表时间：
2017-06-09
影响因子：
4.6
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Zeng S;Yu X;Ma C;Song R;Zhang Z;Zi X;Chen X;Wang Y;Yu Y;Zhao J;Wei R;Sun Y;Xu C
膀胱尿路上皮癌（BLCA）的预后差异很大，即使患者具有相似的病理特征。我们对10对BLCA样本和邻近正常组织进行转录组测序，以鉴定差异表达基因。与正常组织相比，在BLCA样本中，Anillin （ANLN）被鉴定为显著上调的转录物。应用qRT-PCR和免疫组化分别对40例和209例患者的预后能力进行了研究。与低ANLN表达相比，ANLN表达水平升高的患者与较差的癌症特异性（中位数，22.4个月对37.3个月，p = 0.001）、无进展（中位数，19.7个月对27.9个月，p = 0.001）和无复发生存（中位数，17.1个月对25.2个月，p = 0.011）相关。分析公共数据集TCGA和NCBI-GEO进行外部验证。使用小干扰RNA敲除J82和5637细胞中的ANLN，可显著抑制细胞的增殖、迁移和侵袭能力。此外，ANLN的下调导致G2/M期阻滞，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。综上所述，ANLN被认为是一种有前景的预后生物标志物，可用于对BLCA的不同风险进行分层。
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.