Page 31 - GPD-2-3

Gene & Protein in Disease Signatures construction strategies for TC

Figure 5. The flow chart of strategy 3: Signatures based on methylation-related molecules. CoxPH model* means the univariate and multivariate Cox
proportional hazards regression analysis. DEmethylation, differentially expressed methylation.
divided into the BRAFWT group and the BRAFV600E data, we divided the main validation methods into two
group according to the mutation information to identify categories: internal validation and external validation.
DEGs. Furthermore, weighted correlation network Data used to construct a signature were classified into
analysis (WGCNA) function or pathway enrichment, and three main types: the whole dataset, the training set, and
correlation analysis was used to construct a co-expression the testing set. According to the research purpose, the
network. In general, 8 BRAFV600E-associated prognostic verification methods of signatures include the following
biomarkers (FN1, MET, SLC34A2, NGEF, TBC1D2, three categories: (1) the validation methods of prognostic
PLCD3, PROS1, and NECTIN4) were discovered, which signatures were performed in the whole dataset without
could be considered as targets for TC treatment . distinguishing training and testing set [34,42,47,78] ; (2) the
[53]
process of validation was conducted in the training set
3.4. The verification methods of signatures and testing set, respectively [26,28,41] ; and (3) distinguish
In this review, the methods of constructing prognostic among the entire dataset, training set, and testing set, and
signatures were summarized. It is noteworthy that the validate signatures in all three datasets [44,66] . In terms of
validation effects of the constructed signatures could specific verification methods, most researchers adopted
reflect the potential of prognostic signatures for clinical common aforementioned validation approaches, including
application. Through retrospective investigation and Kaplan-Meier survival, ROC curve, and univariate and
integrated analysis, we found that the verification methods multivariate Cox regression analyses. The main methods
described in this review were often closely related to the of internal validation were summarized above.
application of data acquisition and the process of signature A common approach to conducting external validation
construction. Therefore, according to the application of was to employ hospital data sources as the validation

Volume 2 Issue 3 (2023) 15 https://doi.org/10.36922/gpd.1138