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Gene & Protein in Disease Signatures construction strategies for TC

of methylation in the clinical prognosis of TC has been
References Chen et al., 2020 [78] Li et al., 2019 [28] widely recognized [64,65] . In strategy 3, these studies
included not only methylation-driven genes but also
[47]
. In particular, regulators
regulators of methylation
[48,49,66]
of m6A RNA methylation were considered important
Multivariate Cox regression analysis P‑value 95% HR CI P = 0.019 1.09 – 1.79 2.94 P < 0.001 5.94 – 29.05* 142.074 risk predictors [48,49,66] . Through comprehensive analysis,
the steps to build these signatures were as follows:
(1) transcriptome, methylation data, and relevant clinical
information were downloaded from databases, and
samples contained both tumor and normal tissues; (2) the
key methylation-driven genes or regulators of methylation

were constructed by function enrichment analyses
;
[47,66]
Univariate Cox regression analysis P‑value 95% HR CI P = 1.52 – 2.13 0.00001 2.99 P < 0.001 10.231 – 50.097* 245.312 were screened through various analyses; (3) signatures
and (4) Cox regression analysis, ROC, and survival curve
were applied to verify the prognostic capabilities of these
signatures. The flow chart of strategy 3 is shown in Figure 5
and the summarized relevant information of strategy 3 is
In detail, based on methylation-driven genes, Lv
AUC of the ROC curve 1-, 3- and 5-year AUCs: 0.731,0.746 and 0.766 AUC of 3,5 and 10-year survival rates: 0.948,0.965 and 0.949 presented in Table 3. [47]
et al. constructed a 4-gene signature composed of RDH5,
BIRC7, TREM1, and SLC26A7 . Transcriptome data from
567 samples and DNA methylation data from 570 samples
Risk score Risk score= −5.367*cg17749033 + 1.619*cg24221648 + 2.334*cg01664864 + 1.873 *cg09578568 − 3.486*cg24051057 + 5.693*cg05972352 EpiLncPM = 13.1 * AP006248.2 + 2.53 * AC068580.3 + 33.2 * AC016396.2 + 3.12 * LINC01140 + 1.19 * LINC01135 Abbreviations: TC: Thyroid cancer; PTC: Papillary thyroid cancer; DTC: Differentiated thyroid cancer; WDTC: Well-differentiated thyroid cancer; OS: Overall survival; RFS: Recurrence-free s
(46 hypermethylation and 5 hypomethylation) using
“MethylMix” and “limma” R package. In addition, after Cox
regression analysis, the methylation-driven gene signature
was established and validated by the Kaplan-Meier survival

Survival curve P‑value Cut‑off P = 0.0001 The median risk score P < 0.001 The optimal risk cutoff point curve, certifying that patients in the high-risk group
presented a worse prognosis . Besides, Xu et al., Hou
[47]
et al., and Wang et al. also discovered that the m6A RNA
methylation regulators have a high-risk evaluation potency.
Survival event RFS OS Xu et al. and Wang et al. constructed two signatures of 4
[48,66]
RNA methylation regulators, respectively
, whereas
Hou et al. selected RBM15, FTO, and KIAA1429 to establish
[49]
a 3-gene signature . By comparing the differentially
Signatures outcome Unfavorable Unfavorable expressed m6A RNA methylation regulators, they selected
13 RNA methylation regulators. Cox and lasso regression
analyses were applied to assess the relationship between
Signatures A 6-DNA methylation signature A methylation- driven 5-lncRNA -based signature OS and these methylation regulators. Thus, this 3-gene
signature was constructed and validated.
3.3.4. Other strategies
Signatures type DNA methylation sites methylation -driven lncRNA prognostic signatures are associated with a worse prognosis. In addition to the three main aforementioned strategies,
few studies adopted other strategies to identify
signatures
, and the summarized relevant information
[50-54]
of these strategies is presented in Table 4.
Table 3. (Continued) Pathological Authors type PTC Hengyu Chen, et al., 2020 TC Qiuying Li, et al., 2020 3.3.4.1. Signatures related to glucose metabolism

Increasing evidence has demonstrated that glucose
metabolism and glucose transporters (GLUTs) play
essential roles in TC progression
. Suh et al. have studied
[67-70]

Volume 2 Issue 3 (2023) 12 glucose metabolism by constructing GLUT signature and
https://doi.org/10.36922/gpd.1138