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Page 89 Comertpay et al. J Transl Genet Genom 2022;6:84-94 https://dx.doi.org/10.20517/jtgg.2021.44

Table 1. Biological features of seed genes
AGTR1 It is a considerable effector in the cardiovascular system that controls blood pressure and volume
CCND1 It is associated with the cyclin family and their regulatory CDK kinases
GRIA2 It is activated in a variety of ordered neurophysiological processes
GYG2 The gene is associated with initiation reactions of glycogen biosynthesis and involved in blood glucose homeostasis
IL6ST The activation of this protein is dependent on the binding of cytokines to their receptors
MMP9 Its family is concerned with the breakdown of the extracellular matrix in regular physiological processes (embryonic development,
tissue remodeling, etc.) and disease processes such as metastasis
PRKAR2B PKA is related to the organizing of lipid and glucose metabolism
S100A2 It may act as a calcium sensor and modulator, indirectly playing a role in various physiological processes

Table 2. Significant enrichment analyses results
Pathways P-value DEGs
RAF-independent MAPK1/3 activation 0.0006 DUSP4, IL6ST
Collagen degradation 0.0013 MMP12, MMP9
Bladder cancer 0.0018 CCND1, MMP9
Drug metabolism-cytochrome P450 0.0051 FMO2, ADH1B
Signaling by Hedgehog 0.0068 SCUBE2, PRKAR2B
Pathways in cancer 0.0077 CCND1, AGTR1, IL6ST, MMP9
Prostate cancer 0.0096 CCND1, MMP9
AGE-RAGE signaling pathway in diabetic complications 0.0100 CCND1, AGTR1
Degradation of the extracellular matrix 0.0112 MMP12, MMP9
Phase I functionalization of compounds 0.0116 FMO2, ADH1B
Thyroid hormone signaling pathway 0.0135 CCND1, PLN
Apelin signaling pathway 0.0185 CCND1, AGTR1
Adrenergic signaling in cardiomyocytes 0.0203 PLN, AGTR1
Hepatitis B 0.0203 CCND1, MMP9
Cushing syndrome 0.0231 CCND1, AGTR1
JAK-STAT signaling pathway 0.0253 CCND1, IL6ST
cGMP-PKG signaling pathway 0.0256 PLN, AGTR1
Calcium signaling pathway 0.0324 PLN, AGTR1
Kaposi sarcoma-associated herpesvirus infection 0.0327 CCND1, IL6ST
cAMP signaling pathway 0.0370 GRIA2, PLN
Proteoglycans in cancer 0.0377 CCND1, MMP9
Viral carcinogenesis 0.0377 CCND1, IL6ST
MAPK1/MAPK3 signaling 0.0380 DUSP4, IL6ST
Transmission across chemical synapses 0.0455 GRIA2, ABAT
Biological oxidations 0.0466 FMO2, ADH1B
DEGs: Differentially expressed genes.

Gene and pathway relationships were established, and Ridge regression machine learning analysis was
performed [Figure 4]. CCND1, GRIA2, IL6ST, MMP9, and PRKAR2B were determined as molecular
signatures of obese breast cancer patients according to Ridge regression results.

DISCUSSION
The obesity epidemic is recognized as one of the most serious health issues affecting public health
worldwide today. Numerous observational studies have shown that it is associated with obesity and poor