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Gene & Protein in Disease                                           Signatures construction strategies for TC



                                                               essential to verify the prognostic effect of this signature. By
                                                               calculating the risk score and determining the cutoff value,
                      References  Wang   et al., 2020 [66]  Wang   et al., 2020 [66]  patients were divided into high-risk and low-risk groups.
                                                               The survival curve showed a better prognosis in the low-
                                                               risk group than in the high-risk group. Furthermore, the
                                                               area under the  receiver  operating characteristic  (ROC)
                      Multivariate Cox analysis  P‑value HR (95% CI)  P<0.001  1.030   (1.018, 1.042)  P<0.001  1.040   (1.021, 1.059)  curve (AUC) and Harrell’s concordance index (C-index;
                                                               0.7600)  also  demonstrated  that  this  signature  has  a
                                                               remarkable prognostic ability.
                                                               3.3.2. Strategy 2: Signatures related to specific
                                                               biological functions
                                                               In strategy 2, these signatures were built based on
                                      P<0.001
                      Univariate Cox analysis  HR (95% CI)  1.032 (1.022,   1.042)  1.047 (1.030,   1.065)  signatures was as follows: (1) Identification of differential
                            P<0.001
                         P‑value
                                                               biological functions. The process of constructing
                                                               expression genes/lncRNAs. Most authors downloaded
                                                               available transcriptome data from various databases
                                                                                                         [22,23,30]
                                                               or hospitals
                                                                           ; (2) identification of genes associated with
                                                                        [27,32]
                                                               specific biological functions, mainly containing immune-
                                                               from the immunology database
                                                                                               and the Human
                                                                                          [24-26]
                      Signature   outcome  Unfavorable  Unfavorable  related and autophagy-related genes, which were derived
                                                                                          , respectively. Moreover,
                                                                                       [22,23]
                                                               Autophagy Database (HADb)
                                                                                                           [30]
                                                               gene functions associated with RNA-binding proteins ,
                                                                            ,  EMT ,  and  glycolysis   were  all
                                                                                  [45]
                                                                                                  [32]
                                                               ferroptosis
                                                                       [27,31,46]
                      AUC of the ROC   curve  AUC of the   first, third, and   fifth years in the   training set were   0.83, 0.82, and 0.82  AUC of the   first, third, and   fifth years in the   training set were   0.75, 0.84, and 0.85 Abbreviations: OS: Overall survival; DFS: Disease-free survival; PFI: Progression-free interval. Li et al. 2017 a  means the data were derived from the training set in this study; Wang et al. 2020 b   means this study identified three prog
                                                               functions are illustrated in detail below; (3) integrate and
                                                               analyze the molecules to obtain differentially expressed
                                                               biological function-related genes or lncRNAs, followed
                                                               by functional enrichment analyses being performed; and
                      Survival curve  P‑value  P=0.000002462  P=0.00005696  (4) establishment of prognostic signatures. To construct
                                                               a prognostic gene signatures, studies based on strategy
                                                               2 adopted the Cox proportion hazards regression model
                                                               and introduced the risk score formula to stratify TC
                                                               patients [22-27,30-32,45] ; and (5) validation of signatures.
                      Survival   event  PFI  PFI               Methods of verification included Kaplan-Meier survival
                                                               curves, ROC curves, and univariate and multivariate Cox
                                                                                      . The flow  chart of strategy
                                                               regression analyses
                                                                              [24-27,30-32,46]
                                                               2 is shown in  Figure  4 and the summarized relevant
                                                               information of signatures based on strategy 2 is presented
                                                                 According to strategy 2, several functional signatures
                      Signature  PIMREG, PAQR4,   RHBDL1, JAKMIP3,   GAS2L2, and PLEKHG4  AC136475.1, LINC02154,   AC010969.1, and   AC064805.2  patients with a high risk of prognostic signatures are associated with a worse prognosis.  in Table 2.  [26]  [22-26] .
                                                               associated with IRGs and ARGs were established
                                                               Xue et al. developed a 5-immune-associated genes (IAGs)
                                                               signature  to  predict  TC  progression  for  patients .  The
                                                               construction strategy was described as follows: on the
                  Table 1. (Continued)  Signature   Author  type  mRNA  Kun Wang,   et al., 2020 b  lncRNA  one hand, 509 TC and 58 normal samples were obtained
                                                               from the TCGA database; on the other hand, a list of
                                                               2498 IAGs was acquired from the Immunology Database
                                                               (ImmPort). Eighty-two differentially expressed IAGs were
                                                               then screened by an integrated analysis. After univariate,
                                                               multivariate, and lasso regression analyses, a reliable



            Volume 2 Issue 3 (2023)                         7   5-IAGs signature was constructed, including CXCL5,
                                                                                     https://doi.org/10.36922/gpd.1138
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