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Gene & Protein in Disease                                           Signatures construction strategies for TC




                        References  Xu et al.,   2021 [39]     AZU1, NOD1, TNFRSF11B, and VGF. To verify the
                                                               prognostic effect of this signature, samples were divided
                                                               into high- and low-risk groups by risk score. The survival
                                                               curve showed that the high-risk group presented a poor
                        Multivariate Cox   analysis  P‑value  HR (95%   CI)  P < 0.001  1.04 (1.03   – 1.06)  prognosis. The ROC curve also indicated the predictive
                                                               power  of  this  signature.  Other  immune-  or  autophagy-
                                                               related studies also adopted similar signature construction
                                                               methods.
                                                                 In recent years, some studies manifested that ferroptosis
                        Univariate Cox analysis  P‑value HR (95% CI)  P < 0.001  1.05   (1.04 – 1.07)  could  be  linked  to  various  types  of  cancers [57-60] .  Thus,
                                                               some researchers have explored the relationship between
                                                               ferroptosis and thyroid cancer and constructed ferroptosis-
                                                               related signatures with high prognostic values
                                                                                                        . By an
                                                                                                   [27,31,46]
                                                               integrated analysis of DEGs and ferroptosis-related genes, a
                                                               5-gene prognostic signature was discovered, which consisted
                                                               of DPP4, HMGCR, TFRC, PGD, and GSS . Similarly, an
                                                                                                [31]
                                                               8-gene signature containing GPX4, AKR1C1, SQLE, and 5
                                                               aforementioned genes was constructed. Moreover, analysis
                        AUC of the   ROC curve  0.929          of immune microenvironment and nomogram verification
                                                               was performed to validate an 8-gene signature . These
                                                                                                      [27]
                                                               two signatures (5-gene vs. 8-gene) exhibited different AUC
                        Signature   outcome  Unfavorable       values of ROC curves, indicating the difference in their
                                                               predictive abilities. In addition, Lin et al. also constructed
                                                               a ferroptosis-related 7-gene signature (Apoe, Acap3, Bcl3,
                                                      Unfavorable means patients with a high risk of prognostic signatures are associated with a worse prognosis.
                                                               Ac008063.2, Alox5ap, B2m, and Atxn2l) by comparatively
                                 Risk score = (0.0149 * TGFBI   expression level) + (0.0517   * STC1 expression level) +   (1.866 * PPFIA4 expression   level) + (0.345 * POM121C   expression level) + (0.542   * CHST6 expression level)   + (2.672 * FBP2 expression  Abbreviation: PFI: Progression-free interval; OS: Overall survival; IRGs: Immune-related genes; ARGs: Autophagy-related genes; RBPs: RNA binding proteins; ERGs: EMT-related genes.   of tumors . Li  et al. screen
                                                               analyzing two different PTC subtypes .
                                                                                            [46]
                                                                 EMT has been regarded as an indicator in many types
                                                                       [61]
                                                               and KIT) by analyzing the differentially expressed EMT-
                                                               related  genes,  thus  a  3-gene  signature  associated  with
                        Risk score               level)        EMT was established for the prognosis of TC patients ,
                                                                                                           [45]
                                                               as the survival curve illustrated that the high-risk group
                                                               has a worse prognosis than the low-risk group. It has been
                                                               reported that RNA-binding proteins (RBPs) play a critical
                        Survival   curve  P‑value  P = 0.0007  role in the post-transcriptional regulation of RNA and thus
                                                               may affect the occurrence and development of cancer .
                                                                                                           [30]
                                                               By analyzing the differently expressed RBPs, combined
                        Survival   event                       with pathway and functional enrichment analyses, Ma
                                                               et al. constructed a 6-gene prognostic signature (NUDT16,
                                 OS
                                                               NUP153, IGF2BP2, MEX3A, USB1, and AZGP1), which
                                                               may provide a novel strategy for the risk prediction of
                                                                 [30]
                        Signature  CHST6,   POM121C,   PPFIA4, STC1,   TGFBI, and   FBP2  TC . Using the similar methods described above, Xu et al.
                                                               selected 6 glycolysis-related genes (POM121C, PPFIA4,
                                                               FBP2, CHST6, STC1, and TGFBI) to set  up a 6-gene
                                                               prognostic signature . The AUC value of this signature is
                                                                               [32]
                    Table 2. (Continued)  Signature   Authors  type  Glycolysis-   Feng Xu,   based genes  et al., 2021  0.929, indicating its reliable prognostic ability.
                                                               3.3.3. Strategy 3: Signatures associated with
                                                               methylation

                                                               In recent years, epigenetic regulation has been found



                                                                                     https://doi.org/10.36922/gpd.1138
            Volume 2 Issue 3 (2023)                         10   to be crucial for gene expression [62,63] . The importance
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