A four-gene signature for prognosis in breast cancer patients with hypermethylated IL15RA
A four-gene signature for prognosis in breast cancer patients with hypermethylated IL15RA
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DOI：
10.3892/ol.2019.10137
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发表时间：
2019-05-01
期刊：
影响因子：
2.9
通讯作者：
Qian, Jun
中科院分区：
文献类型：
--
作者：
Yang, Hui;Zhou, Li;Qian, Jun
先前的研究表明，白细胞介素15受体（IL 15 RA）的上调有助于改善乳腺癌的预后。本研究旨在阐明IL 15 RA上调诱导的抗肿瘤作用的分子机制，并确定能够预测乳腺癌患者生存的基因特征。使用来自癌症基因组图谱数据门户的乳腺癌样品的配对基因表达和甲基化数据，在高甲基化和低甲基化的IL 15 RA乳腺癌样品中鉴定差异表达基因（DEG）。根据生存相关DEGS的考克斯回归系数建立了基于基因特征的风险评分模型。通过Kaplan-Meier生存分析总生存（OS）时间，应用基因签名将患有乳腺癌和高甲基化IL 15 RA的患者分为两个风险组。进行了功能富集分析，以破译两个风险组之间的DEG的生物学作用。与正常样本相比，低甲基化和高甲基化样本中共有326个DEG。四基因签名[SH 3和富含半胱氨酸的结构域2（STAC 2）、富含脯氨酸的11（PRR 11）、同源框C11（HOXC 11）和核仁和纺锤体相关蛋白1（NUSAP 1）]被鉴定为能够成功地将患有乳腺癌和高甲基化IL 15 RA的患者分成具有显著不同OS时间的两个风险组。该签名在一个独立的集合中显示出类似的预测性能。两个风险组之间发生了涉及DEG的受体相互作用和细胞粘附分子（CAM）途径的显著富集。这些结果表明，IL 15 RA可能参与调节STAC 2、PRR 11、HOXC 11、NUSAP 1和ECM-受体相互作用以及细胞粘附分子的通路，从而抑制乳腺癌的发生和发展。四基因标记可能对乳腺癌具有潜在的预后价值。
Previous studies have revealed that upregulation of interleukin 15 receptor (IL15RA) contributes to improved prognosis of breast cancer. The present study aimed to elucidate the molecular mechanisms underlying the antitumor effect induced by IL15RA upregulation, and to identify a gene signature capable of predicting the survival of patients with breast cancer. Using paired gene expression and methylation data of breast cancer samples from The Cancer Genome Atlas data portal, differentially expressed genes (DEGs) were identified in hypermethylated and hypomethylated IL15RA breast cancer samples. Furthermore, a gene signature-based risk-scoring model was developed according to the Cox regression coefficients of survival-associated DEGS. The gene signature was applied to classify patients with breast cancer and hypermethylated IL15RA into two risk groups via Kaplan-Meier survival analysis of overall survival (OS) time. Functional enrichment analysis was conducted to decipher the biological roles of the DEGs between the two risk groups. A total of 326 DEGs were present in the hypomethylation and hypermethylation samples compared with in the normal samples. A four-gene signature [SH3 and cysteine rich domain 2 (STAC2), proline rich 11 (PRR11), homeobox C11 (HOXC11) and nucleolar and spindle associated protein 1 (NUSAP1)] was identified as able to successfully separate patients with breast cancer and hypermethylated IL15RA into two risk groups with significantly different OS time. The signature revealed similar predictive performance in an independent set. Significant enrichment of the receptor interaction' and cell adhesion molecules (CAM)' pathways, which involved the DEGs, occurred between the two risk groups. These findings suggested that IL15RA may participate in the regulation of STAC2, PRR11, HOXC11, NUSAP1, and ECM-receptor interaction' and cell adhesion molecules' pathways, and therefore in the suppression of breast cancer development and progression. The four-gene signature may have potential prognostic value for breast cancer.