Kidney renal cell carcinoma (KIRC), which is the most common subtype of kidney cancer, has a poor prognosis and a high mortality rate. In this study, a multi-omics analysis is performed to build a multi-gene prognosis signature for KIRC. A combination of a DNA methylation analysis and a gene expression data analysis revealed 863 methylated differentially expressed genes (MDEGs). Seven MDEGs (BID, CCNF, DLX4, FAM72D, PYCR1, RUNX1, and TRIP13) were further screened using LASSO Cox regression and integrated into a prognostic risk score model. Then, KIRC patients were divided into high- and low-risk groups. A univariate cox regression analysis revealed a significant association between the high-risk group and a poor prognosis. The time-dependent receiver operating characteristic (ROC) curve shows that the risk group performs well in predicting overall survival. Furthermore, the risk group is contained in the best multivariate model that was obtained by a multivariate stepwise analysis, which further confirms that the risk group can be used as a potential prognostic biomarker. In addition, a nomogram was established for the best multivariate model and shown to perform well in predicting the survival of KIRC patients. In summary, a seven-MDEG signature is a powerful prognosis factor for KIRC patients and may provide useful suggestions for their personalized therapy.

As one of the most common malignancies in the world, lung adenocarcinoma (LUAD) is currently difficult to cure. However, the advent of precision medicine provides an opportunity to improve the treatment of lung cancer. Subtyping lung cancer plays an important role in performing a specific treatment. Here, we developed a framework that combines k-means clustering, t-test, sensitivity analysis, self-organizing map (SOM) neural network, and hierarchical clustering methods to classify LUAD into four subtypes. We determined that 24 differentially expressed genes could be used as therapeutic targets, and five genes (i.e., RTKN2, ADAM6, SPINK1, COL3A1, and COL1A2) could be potential novel markers for LUAD. Multivariate analysis showed that the four subtypes could serve as prognostic subtypes. Representative genes of each subtype were also identified, which could be potentially targetable markers for the different subtypes. The function and pathway enrichment analyses of these representative genes showed that the four subtypes have different pathological mechanisms. Mutations associated with the subtypes, e.g., epidermal growth factor receptor (EGFR) mutations in subtype 4 and tumor protein p53 (TP53) mutations in subtypes 1 and 2, could serve as potential markers for drug development. The four subtypes provide a foundation for subtype-specific therapy of LUAD.

As liver hepatocellular carcinoma (LIHC) has high morbidity and mortality rates, improving the clinical diagnosis and treatment of LIHC is an important issue. The advent of the era of precision medicine provides us with new opportunities to cure cancers, including the accumulation of multi-omics data of cancers. Here, we proposed an integration method that involved the Fisher ratio, Spearman correlation coefficient, classified information index, and an ensemble of decision trees (DTs) for biomarker identification based on an unbalanced dataset of LIHC. Then, we obtained 34 differentially expressed genes (DEGs). The ability of the 34 DEGs to discriminate tumor samples from normal samples was evaluated by classification, and a high area under the curve (AUC) was achieved in our studied dataset and in two external validation datasets (AUC = 0.997, 0.973, and 0.949, respectively). Additionally, we also found three subtypes of LIHC, and revealed different biological mechanisms behind the three subtypes. Mutation enrichment analysis showed that subtype 3 had many enriched mutations, including tumor protein p53 (TP53) mutations. Overall, our study suggested that the 34 DEGs could serve as diagnostic biomarkers, and the three subtypes could help with precise treatment for LIHC.

Aberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we used a computational framework to investigate the roles of transcription factors (TFs) on regulating RBP-AS interactions. A total of 6519 TF–RBP–AS triplets were identified, including 290 TFs, 175 RBPs, and 16 ASEs from TCGA–KIRC RNA sequencing data. TF function categories were defined according to correlation changes between RBP expression and their targeted ASEs. The results suggested that most TFs affected multiple targets, and six different classes of TF-mediated transcriptional dysregulations were identified. Then, regulatory networks were constructed for TF–RBP–AS triplets. Further pathway-enrichment analysis showed that these TFs and RBPs involved in triplets were enriched in a variety of pathways that were associated with cancer development and progression. Survival analysis showed that some triplets were highly associated with survival rates. These findings demonstrated that the integration of TFs into alternative splicing regulatory networks can help us in understanding the roles of alternative splicing in cancer.