Extracellular Matrix-Related Six-lncRNA Signature as a Novel Prognostic Biomarker for Bladder Cancer.
Extracellular Matrix-Related Six-lncRNA Signature as a Novel Prognostic Biomarker for Bladder Cancer.
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DOI：
10.2147/ott.s284167
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发表时间：
2020
影响因子：
4
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Qing L;Gu P;Liu M;Shen J;Liu X;Guang R;Ke K;Huang Z;Lee W;Zhao H
膀胱癌（BC）是第四大常见癌症，也是男性癌症相关死亡的第六大原因。然而，缺乏可靠的生物标志物仍然是 BC 预后和治疗的一个问题。 lncRNA已被证明在各种癌症中发挥重要作用，并已成为癌症预后和治疗的有前途的生物标志物。在本研究中，我们使用单变量和多变量Cox回归分析，检查了TCGA BLCA队列中1,651个lncRNA的差异表达谱，并创建了由6个lncRNA（SNHG12、MAFG-DT、ASMTL-AS1、LINC02321、LINC01322和LINC00922）组成的预后基因特征，设计了SMALLL特征。 SMALLL 特征显示了多个队列中 BC 患者总体生存的显着预后能力。基因本体分析表明，与 SMALLL 特征共表达的基因与细胞外基质网络相关，免疫细胞浸润分析表明，高风险组和低风险组中激活的幼稚 B 细胞、调节性 T 细胞、M0 巨噬细胞、嗜酸性粒细胞、静息记忆 CD4 T 细胞和静息 NK 细胞存在显着差异。我们还通过 qRT-PCR 分析证实了 BC 组织和癌旁正常组织中 SMALLL 特征的 lncRNA 的差异表达。细胞侵袭和迁移实验表明，MAFG-AS1、ASMTL-AS1、LINC02321和LINC00922显着影响细胞侵袭和迁移。我们的研究表明，lncRNA 特征是预后的重要预测因素，并为 BC 提供了一种有前途的生物标志物。
Bladder cancer (BC) is the fourth-commones cancer and the sixth-leading cause of cancer-related death among men. However, a lack of reliable biomarkers remains a problem forprognosis and treatment of BC. lncRNAs have been shown to play important roles in various cancers, and have emerged as promising biomarkers for cancer prognosis and treatment. In this study, using univariate and multivariate Cox regression analysis, we examined the differential expression profiles of 1,651 lncRNAs in the TCGA BLCA cohort and created a prognostic gene signature composed of six lncRNAs (for SNHG12, MAFG-DT, ASMTL-AS1, LINC02321, LINC01322, and LINC00922), designed the SMALLL signature. The SMALLL signature displayed significant prognostic power for overall survival for BC patients in multiple cohorts. Gene Ontology analysis showed that genes coexpressed with the SMALLL signature were associated with the extracellular matrix network, and immune cell–infiltration analysis showed that activated naïve B cells, regulatory T cells, M0 macrophages, eosinophils, resting memory CD4 T cells and resting NK cells were significantly different in high- and low-risk groups. We also confirmed differential expression of the lncRNAs of the SMALLL signature in BC tissue and paracancer normal tissue by qRT-PCR analysis. Cell-invasion and -migration experiments showed that MAFG-AS1, ASMTL-AS1, LINC02321, and LINC00922 significantly affected cell invasion and migration. Our study revealed that the lncRNA signature is an important predictive factor of prognosis and provides a promising biomarker for BC.