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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

