Table_4_Identification of Pan-Cancer Prognostic Biomarkers Through Integration of Multi-Omics Data.XLSX

Prognostic biomarkers dedicating to treat cancer are very difficult to identify. Although high-throughput sequencing technology allows us to mine prognostic biomarkers much deeper by analyzing omics data, there is lack of effective methods to comprehensively utilize multi-omics data. In this work, we integrated multi-omics data [DNA methylation (DM), gene expression (GE), somatic copy number alternation, and microRNA expression (ME)] and proposed a method to rank genes by desiring a “Score.” Applying the method, cancer-specific prognostic biomarkers for 13 cancers were obtained. The prognostic powers of the biomarkers were further assessed by C-indexes (ranged from 0.76 to 0.96). Moreover, by comparing the 13 survival-related gene lists, seven genes (SLK, API5, BTBD2, PTAR1, VPS37A, EIF2B1, and ZRANB1) were found to be associated with prognosis in a variety of cancers. In particular, SLK was more likely to be cancer-related due to its high missense mutation rate and associated with cell adhesion. Furthermore, after network analysis, EPRS, HNRNPA2B1, BPTF, LRRK1, and PUM1 were demonstrated to have a broad correlation with cancers. In summary, our method has a better integration of multi-omics data that can be extended to the researches of other diseases. And the prognostic biomarkers had a better prognostic power than previous methods. Our results could provide a reference for translational medicine researchers and clinicians.

针对癌症治疗的预后生物标志物的识别极为艰难。尽管高通量测序技术使我们能够通过分析组学数据，更深入地挖掘预后生物标志物，但仍缺乏有效的方法来全面利用多组学数据。在本研究中，我们整合了多组学数据[包括DNA甲基化（DM）、基因表达（GE）、体细胞拷贝数变异和microRNA表达（ME）]，并提出了一种通过“评分”对基因进行排序的方法。应用此方法，我们获得了13种癌症的癌症特异性预后生物标志物。这些生物标志物的预后能力通过C指数（范围从0.76到0.96）进行了进一步评估。此外，通过比较13个与生存相关的基因列表，我们发现七个基因（SLK、API5、BTBD2、PTAR1、VPS37A、EIF2B1和ZRANB1）与多种癌症的预后相关。特别是，SLK由于其高错义突变率和与细胞粘附的关联，更有可能与其癌症相关性有关。进一步的网络分析表明，EPRS、HNRNPA2B1、BPTF、LRRK1和PUM1与癌症具有广泛的关联性。总之，我们的方法在多组学数据的整合方面具有更好的表现，可扩展应用于其他疾病的研究。而且，这些预后生物标志物相较于以往方法具有更强的预后能力。我们的研究结果可为转化医学研究人员和临床医生提供参考。