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Gene & Protein in Disease                                           Signatures construction strategies for TC



            cohort. For instance, the internal validation was   of  TC  by  constructing  the  risk  assessment  models:
            performed using transcriptome and clinical data of PTC   nomograms [19,27,36,38,56,78] .
            patients derived from the Nucleotide Archive database,   Nowadays, nomogram can be widely used for combining
            and the external validation was employed by inducing   diagnosis with multiple indexes and also predict the
            11  patients who had undergone total thyroidectomy in   recurrence and progression of many carcinomas, including
            Beijing Cancer Hospital . In addition, Liu et al. and Lv   [19,38,56]  [78]  [36]  [27]
                               [21]
            et al. acquired the patients’ data from the hospitals and   PFI  , RFS , DFS , and OS  for DTC, PTC, or TC
            performed further validation in the regulation of each   patients. Based on the prognostic signature established
            molecule of the signature [29,47] . In addition to statistical   by the multivariate regression hazard model and some
            validation methods, some studies also used experimental   relative clinical parameters, the nomogram could be
            validation methods such as immunohistochemistry (IHC)   developed. The assessment indexes including the C-index,
            and quantitative real-time polymerase chain reaction   AUC of ROC, and the calibration plots could evaluate the
            (qRT-PCR). As effective external validation methods,   performance of the nomogram [19,36,38,78] . For instance, Pan
            IHC and qRT-PCR were used to verify the differential   et al. screened 5 genes to establish a prognostic signature
            expression of the biomarkers during the construction and   and then validated its prognostic value for clinical
            validation of signatures [25,29,31,33,45,79] . As common methods   applications. In addition, a nomogram of predicting
            of experimental verification, both of them could further   DFS of PTC patients was constructed with a C-index of
            verify the expression level of molecules in prognostic tags,   0.797  (95% CI, 0.730–0.864), and AUCs for 1-, 3-, and
                                                                                                           [36]
            making the signatures more convincing.             5-year DFS were 0.763, 0.777, and 0.755, respectively .
                                                               Chen  et al. identified a DNA-methylated signature that
            3.5. Nomogram based on prognostic signatures for TC  has a good performance for RFS of PTC and then based
            To demonstrate the prognostic abilities of signatures, some   on the risk score and multivariate regression model, a
            studies predicted the risk of various outcome variables   nomogram utilized in the clinic was constructed . Wang
                                                                                                      [78]

            Table 5. Nomograms constructed for prognostic signatures of TC patients
            Author      Signatures   Pathological   Survival   Nomogram validation methods      References
                        type      type      event   AUCs of the ROC   Harrell’s   P‑value   Calibration
                                                    curve (95% CI)  concordance   of K‑M   plot
                                                                  index (95% CI)  analysis
            Ruchong Pan,   mRNA   DTC       DFS     AUCs for 1-, 3-, and  0.797 (95% CI,   Yes  Ruchong
            et al., 2021                            5-year DFS: 0.763,   0.730 – 0.864)         et al., 2021 [36]
                                                    0.777, and 0.755
            Zhiwei Chen,   mRNA   TC        OS                                         Yes      Chen
            et al., 2021                                                                        et al., 2021 [79]
            Mingqin Ge,   mRNA    TC        OS                                         Yes      Ge
            et al., 2021                                                                        et al., 2021 [27]
            Mengwei Wu,   mRNA    PTC       PFI     The AUCs for the 1-,  0.790 (95% CI,   P<0.0001  Yes  Wu
            et al., 2020                            3-, and 5-year PFI:   0.652 – 0.927)        et al., 2020 [38]
                                                    0.855 (95% CI, 0.779
                                                    – 0.932), 0.799 (95%
                                                    CI, 0.722 – 0.877),
                                                    and 0.812 (95% CI,
                                                    0.718 – 0.907)
            Mengwei Wu,   mRNA    PTC       PFI     The AUCs for the 1-,  0.7600 (95% CI,   P<0.0001  Yes  Wu
            et al., 2019                            3-, and 5-year PFI:   0.6759 – 0.8440)      et al., 2019 [19]
                                                    0.7480, 0.7550, and
                                                    0.7627
            Kun Wang,   mRNA/     PTC       PFI                   0.792 (95% CI,       Yes      Wang
            et al., 2020  lncRNA                                  0.716 – 0.867)                et al., 2020 [56]
            Hengyu Chen,   DNA    PTC       RFS     The AUCs for 1-,   0.796 (95% CI,   Yes     Chen
            et al., 2020  methylation               3-, and 5-year RFS:   0.704 – 0.888)        et al., 2020 [78]
                                                    0.850, 0.783, and
                                                    0.800
            Abbreviations: PFI: Progression-free intervals; DFS: Disease-free survival; RFS: Recurrence-free survival; OS: Overall survival


            Volume 2 Issue 3 (2023)                         16                       https://doi.org/10.36922/gpd.1138
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