Gene   Parameters Diabetic Foot Ulcers (n=9) Pressure Ulcers (n=5) Acute wound Dif. between means (DFU-PU) (CI 95%) (CI 99%) p value
MTOR Serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription Mean ± SD 0.574 ± 0.393 1.422 ± 0.288 1.154 -0.848 ± 0.202 -1.287 to -0.409 -1.464 to -0.232 0.0012**
Median (25%; 75% percentile) 0.517 (0.169; 0.964) 1.266 (1.193; 1.728) -
(min; max) (0.047; 1.099) (1.126; 1.787) -
E2F1 Transcription factor. Plays a crucial role in the control of cell cycle and action of tumor suppressor proteins Mean ± SD 0.353 ± 0.3381 0.831 ± 0.1878 0.774 -0.478 ± 0.165 -0.838 to -0.117 -0.983 to 0.028 0.0136*
Median (25%; 75% percentile) 0.304 (0.033; 0.720) 0.728 (0.724; 0.988) -
(min; max) (0.001; 0.831) (0.724; 1.159) -
PCNA Cofactor of DNA polymerase delta. Helps increase the processivity of leading strand synthesis during DNA synthesis and repair Mean ± SD 1.264 ± 0.341 1.737 ± 0.496 1.880 -0.472 ± 0.172 -0.850 to -0.094 -1.005 to 0.061 0.019*
Median (25%; 75% percentile) 1.257 (0.938; 1.510) 1.732 (1.532; 1.944) -
(min; max) (0.826; 1.849) (1.444; 1.955) -
CDK4 Catalytic subunit of the protein kinase complex that leads G1 to S phase progression during cell cycle Mean ± SD 1.027 ± 0.377 1.412 ± 0.150 1.566 -0.384 ± 0.178 -0.773 to 0.004 -0.930 to 0.160 0.05*
Median (25%; 75% percentile) 1.145 (0.816; 1.298) 1.440 (1.288; 1.521) -
(min; max) (0.197; 1.395) (1.156; 1.527) -
COL1A1 Fibrillar collagen found in most connective tissues that strengthens and supports many tissues in the body, including cartilage, bone, tendon, skin and sclera Mean ± SD 0.966 ± 0.474 1.448 ± 0.117 1.432 -0.482 ± 0.166 -0.855 to -0.109 -1.015 to 0.050 0.016*
Median (25%; 75% percentile) 0.940 (0.692; 1.336) 1.377 (1.359; 1.572) -
(min; max) (0.113; 1.670) (1.344; 1.606) -
COL3A1 Collagen of granulation tissue, it is produced quickly by young fibroblasts before the tougher type I collagen is synthesized. Reticular fiber. Also found in artery walls, skin, intestines and the uterus Mean ± SD 0.937 ± 0.392 1.498 ± 0.117 1.421 -0.5606 ± 0.1409 -0.873 to -0.247 -1.005 to -0.116 0.0025**
Median (25%; 75% percentile) 1.138 (0.568; 1.286) 1.451 (1.410; 1.610) -
(min; max) (0.278; 1.360) (1.393; 1.685) -
TGFB1 Multifunctional cytokine that regulates proliferation, differentiation, adhesion, migration, and other functions in many cell types. TGF-beta is a key regulator of ECM assembly and remodeling. It inhibits the synthesis of extracellular proteinases while upregulating the production of their inhibitors and that of structural ECM components, such as collagen Mean ± SD 1.266 ± 0.524 1.838 ± 0.183 2.065 -0.572 ± 0.246 -1.107 to -0.036 -1.323 to 0.179 0.038*
Median (25%; 75% percentile) 1.118 (0.924; 1.782) 1.825 (1.667; 2.015) -
(min; max) (0.368; 1.876) (1.661; 2.093) -
INSR Transmembrane receptor that mediates the biological effects of insulin Mean ± SD 0.626 ± 0.375 1.242 ± 0.176 1.282 -0.617 ± 0.180 -1.009 to -0.225 -1.167 to -0.067 0.005**
Median (25%; 75% percentile) 0.643 (0.258; 0.976) 1.184 (1.110; 1.405) -
(min; max) (0.131; 1.166) (1.075; 1.528) -
SLC2A1 Glucose transporter responsible for the low-level of basal glucose uptake required to sustain respiration in all cells Mean ± SD 0.684 ± 0.420 1.658 ± 0.662 1.172 -0.974 ± 0.286 -1.598 to -0.350 -1.849 to -0.099 0.0053**
Median (25%; 75% percentile) 0.714 (0.230; 1.077) 1.935 (0.979; 2.200) -
(min; max) (0.082; 1.214) (0.697; 2.260) -
HK1 Enzyme that localizes to the outer membrane of mitochondria, mediates phosphorylation of glucose to glucose-6-phosphate, the first step in glucose metabolism pathway Mean ± SD 0.933 ± 0.489 1.996 ± 0.385 1.105 -1.064 ± 0.255 -1.619 to -0.509 -1.842 to -0.286 0.0013**
Median (25%; 75% percentile) 0.933 (0.640; 1.346) 2.079 (1.679; 2.273) -
(min; max) (0.001; 1.587) (1.369; 2.413) -
HK2 Predominant form found in skeletal muscle. Expression studies suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells Mean ± SD 0.945 ± 0.457 1.685 ± 0.502 0.926 -0.739 ± 0.288 -1.382 to -0.097 -1.653 to 0.174 0.028*
Median (25%; 75% percentile) 0.916 (0.536; 1.413) 1.702 (1.203; 2.149) -
(min; max) (0.279; 1.465) (1.056; 2.278) -
PFKP Catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate Mean ± SD 1.069 ± 0.283 1.426 ± 0.227 1.554 -0.357 ± 0.148 -0.678 to -0.035 -0.809 to 0.095 0.032*
Median (25%; 75% percentile) 1.139 (0.849; 1.259) 1.491 (1.231; 1.588) -
(min; max) (0.566; 1.465) (1.045; 1.630) -
PKM1 Pyruvate kinase that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate. The pyruvate kinase isoforms PKM1 and PKM2 are alternatively spliced products of the PKM2 gene, from two mutually exclusive exons Mean ± SD 1.520 ± 0.773 2.915 ± 0.728 1.348 -1.395 ± 0.423 -2.317 to -0.474 -2.688 to -0.103 0.0064**
Median (25%; 75% percentile) 1.804 (1.014; 2.149) 3.071 (2.220; 3.533) -
(min; max) (0.001; 2.390) (1.792; 3.563) -
PKM2 The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer Mean ± SD 1.095 ± 0.417 2.203 ± 0.434 1.684 -1.108 ± 0.236 -1.622 to -0.595 -1.828 to -0.388 0.0005***
Median (25%; 75% percentile) 0.910 (0.803; 1.466) 2.321 (1.781; 2.566) -
(min; max) (0.534; 1.796) (1.544; 2.625) -
PDHA1 Enzyme of the pyruvate dehydrogenase mitochondrial multienzyme complex that catalyzes conversion of pyruvate to acetyl-CoA and CO2, and provides the primary link between glycolysis and the tricarboxylic acid cycle Mean ± SD 1.149 ± 0.381 2.025 ± 0.235 1.939 -0.876 ± 0.189 -1.288 to -0.463 -1.454 to -0.297 0.0006***
Median (25%; 75% percentile) 1.220 (0.944; 1.411) 2.016 (1.793; 2.261) -
(min; max) (0.325; 1.621) (1.770; 2.282) -
PDK4 Enzyme of the pyruvate dehydrogenase mitochondrial multienzyme complex that inhibits the pyruvate dehydrogenase complex by phosphorylating PDH subunit Mean ± SD 1.050 ± 0.397 0.457 ± 0.226 1.066 0.538 ± 0.195 0.113 to 0.962 -0.057 to 1.132 0.017*
Median (25%; 75% percentile) 0.796 (0.722; 1.209) 0.520 (0.208; 0.625) -
(min; max) (0.437; 1.770) (0.202; 0.727) -
FOXO3 Transcription factor which triggers apoptosis through expression of genes necessary for cell death. It is also implicated in resistance to oxidative stress by promoting the expression of anti-oxidant defense enzymes such as Mn-SOD and catalase Mean ± SD 1.156 ± 0.404 1.516 ± 0.114 1.969 -0.360 ± 0.144 -0.681 to -0.039 -0.816 to 0.096 0.0313*
Median (25%; 75% percentile) 1.172 (1.013; 1.452) 1.515 (1.417; 1.616) -
(min; max) (0.243; 1.633) (1.340; 1.628) -
SIRT1 Histone deacetylase type III, deacetylates a broad number of nonhistone substrates in a variety of tissues, activating or silencing their biological activities Mean ± SD 0.373 ± 0.152 0.853 ± 0.371 0.813 -0.478 ± 0.173 -0.931 to -0.026 -1.196 to 0.239 0.042*
Median (25%; 75% percentile) 0.339 (0.250; 0.482) 0.836 (0.527; 1.188) -
(min; max) (0.168; 0.643) (0.513; 1.425) -
SOD2 One the most important enzymes for anti-oxidant defense. This is a mitochondrial matrix protein that catalyses the dismutation of toxic superoxide ion into hydrogen peroxide and diatomic oxygen Mean ± SD 1.382 ± 0.232 1.686 ± 0.176 2.281 -0.304 ± 0.120 -0.565 to -0.043 -0.670 to 0.062 0.026*
Median (25%; 75% percentile) 1.294 (1.188; 1.565) 1.750 (1.510; 1.829) -
(min; max) (1.070; 1.782) (1.430; 1.875) -
Gene expression was assessed by semi-quantitative RT-PCR and normalized to ribosomal subunit 18S mRNA. SD: Standard Deviation; min: Minimum; max: Maximum; dif: Difference; CI: Confidence Interval. *p< 0.05, **p < 0.01, ***p< 0.001.
Table 3: Relative gene expression in diabetic foot ulcers, pressure ulcers and acute wound