Department of Urology, China Medical University, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Dermatology, China Medical University, The First Hospital of China Medical University, Shenyang, Liaoning, China.
BMC Cancer. 2021 Jun 24;21(1):727. doi: 10.1186/s12885-021-08356-9.
There is evidence that long non-coding RNA (lncRNA) is related to genetic stability. However, the complex biological functions of these lncRNAs are unclear.
TCGA - KIRC lncRNAs expression matrix and somatic mutation information data were obtained from TCGA database. "GSVA" package was applied to evaluate the genomic related pathway in each samples. GO and KEGG analysis were performed to show the biological function of lncRNAs-mRNAs. "Survival" package was applied to determine the prognostic significance of lncRNAs. Multivariate Cox proportional hazard regression analysis was applied to conduct lncRNA prognosis model.
In the present study, we applied computational biology to identify genome-related long noncoding RNA and identified 26 novel genomic instability-associated lncRNAs in clear cell renal cell carcinoma. We identified a genome instability-derived six lncRNA-based gene signature that significantly divided clear renal cell samples into high- and low-risk groups. We validated it in test cohorts. To further elucidate the role of the six lncRNAs in the model's genome stability, we performed a gene set variation analysis (GSVA) on the matrix. We performed Pearson correlation analysis between the GSVA scores of genomic stability-related pathways and lncRNA. It was determined that LINC00460 and LINC01234 could be used as critical factors in this study. They may influence the genome stability of clear cell carcinoma by participating in mediating critical targets in the base excision repair pathway, the DNA replication pathway, homologous recombination, mismatch repair pathway, and the P53 signaling pathway.
These data suggest that LINC00460 and LINC01234 are crucial for the stability of the clear cell renal cell carcinoma genome.
有证据表明，长非编码 RNA（lncRNA）与遗传稳定性有关。然而，这些 lncRNA 的复杂生物学功能尚不清楚。
从 TCGA 数据库中获取 TCGA-KIRC lncRNA 表达矩阵和体细胞突变信息数据。应用“GSVA”程序包评估每个样本中的基因组相关途径。进行 GO 和 KEGG 分析以显示 lncRNA-mRNA 的生物学功能。应用“Survival”程序包确定 lncRNA 的预后意义。应用多变量 Cox 比例风险回归分析进行 lncRNA 预后模型。
在本研究中，我们应用计算生物学来识别与基因组相关的长非编码 RNA，并在透明细胞肾细胞癌中鉴定了 26 个新的与基因组不稳定性相关的 lncRNA。我们鉴定了一个由基因组不稳定性衍生的基于六个 lncRNA 的基因特征，该特征可将透明肾细胞样本明显分为高风险和低风险组。我们在测试队列中进行了验证。为了进一步阐明这六个 lncRNA 在模型基因组稳定性中的作用，我们对矩阵进行了基因集变异分析（GSVA）。我们在基因组稳定性相关途径的 GSVA 评分和 lncRNA 之间进行了 Pearson 相关性分析。确定 LINC00460 和 LINC01234 可以作为本研究中的关键因素。它们可能通过参与调节碱基切除修复途径、DNA 复制途径、同源重组、错配修复途径和 P53 信号通路中的关键靶标，影响透明细胞癌的基因组稳定性。
这些数据表明，LINC00460 和 LINC01234 对透明细胞肾细胞癌基因组的稳定性至关重要。
