Table 3. Genes with Differentially Methylated CpG Loci in the Progression of Anal Neoplasia.
| Symbol | Product | Annotation | CpG Number* | P-value | |
| MW† | KW‡ | ||||
| Growth Regulation and Cell Cycle Control | |||||
| TGFβ3 | Transforming growth factor,beta 3 | Controls proliferation and differentiation | cg17928876 | 0.0012 | 0.0063 |
| FRK | Fyn-related kinase | SRC kinase family with epithelial tissue-specificexpression | cg26557270 | 0.0054 | 0.0247 |
| PADI4 | Peptidyl arginine deiminase,type IV | Post-translational modification (arginine methylationand citrull-ination) of histones | cg19159961 | 0.0030 | 0.0155 |
| ID1 | Inhibitor of DNA binding 1 isoform a | Helix-loop-helix protein | cg09569033 | 0.0071 | 0.0228 |
| Differentiation | |||||
| S100A2 | S100 calcium binding proteinA2 | Small, acidic Ca(2+)-binding proteins in nucleus | cg09232826; cg21074565 | 0.0015;0.0083 | 0.0040; 0.0325 |
| KRT1 | Keratin 1 | Differentiation-dependent keratin | cg06030058 | 0.0015 | 0.0071 |
| KRT5 | Keratin 5 | Primary keratin | cg04254916 | 0.0033 | 0.0154 |
| PRSS8 | Prostasin pre-protein | Trypsinogen; serine proteases | cg27436259 | 0.0022 | 0.0116 |
| Angiogenesis | |||||
| FLT1 | Fms-related tyrosine kinase 1 | VEGF receptor tyrosine kinase (also VEGFR1) | cg21787743 | 0.0020 | 0.0041 |
| KDR | Kinase insert domain receptor | VEGF Type III receptor tyrosine kinase (also VEGFR2) | cg04695981 | 0.0044 | 0.0197 |
| Apoptosis | |||||
| DAPK1 | Death-associated protein kinase 1 | Calmodulin-dependent serine-threonine kinase | cg01984172 | 0.0021 | 0.0106 |
| HOXA5 | Homeobox A5 | DNA-binding transcription factor | cg27409178 | 0.0037 | 0.0133 |
| TNFRSF10B | Tumor necrosis factor receptor superfamily, 10b | Death domain associated receptor | cg07508317 | 0.0026 | 0.0112 |
| BCL2A1 | BCL2-related protein A1 | Reduces pro-apoptotic cytochrome C release; blocks caspase activation. | cg27177709 | 0.0061 | 0.0262 |
| SEMA3B | Semaphorin 3B isoform 1 | Extracellular secreted protein important in axonal guidance; induces apoptosis | cg12999941 | 0.0083 | 0.0283 |
| Other Processes | |||||
| CCL3 | Chemokine (C-C motif) ligand 3 | Macrophage inflammatory protein-1 | cg05481196 | 0.0096 | 0.0374 |
| P2RX7 | Purinergic receptor P2X7isoform b | Cell surface ATP receptor; ligand-gated ion channel | cg08688169 | 0.0096 | 0.0156 |
| CD9 | CD9 antigen | Cell surface tetraspanin (TM4SF) glycoprotein | cg19415774 | 0.0071 | 0.0228 |
| DIO3 | Deiodinase, iodothyronine, III | Selenoenzyme | cg18191511 | 0.0074 | 0.0133 |
| GABRA5 | Gamma-aminobutyric acid A receptor, alpha 5 | heteromeric pentameric ligand-gated ion channels | cg02225257; cg20051555 | 0.0030; 0.0044 | 0.0112; 0.0044 |
*
CpG locus label within the GoldenGate methylation array.
†
Mann-Whitney test for methylation differences between two groups (pre-invasive vs. invasive SCC) using a conservative threshold to partially correct for multiple testing problems (p<0.01).
‡
Kruskal-Wallis non-parametric test performed to test three levels (Normal, SCC-IS and Invasive).