Table 2.
Ingenuity pathway analysis (IPA, Qiagen, Germantown, MD, USA) was used to assess whether the biomarkers in the literature dataset (n = 32) would participate in the activation of innate and immune mechanisms applicable to reducing endodontic infection, reducing inflammation, and assisting in endodontic tissue healing. Representative IPA canonical pathways annotations were associated with cellular stress and injury; cytokine signaling; cellular immune response. Representative IPA diseases or functions annotations were associated with antimicrobial response, cell-to-cell signaling and interaction, cellular movement, hematological system development and function, immune cell trafficking, and inflammatory response.
| IPA Function | p-Value | No. | Identification of Molecules |
|---|---|---|---|
| Canonical Pathway Annotations | |||
| Cellular Stress and Injury | |||
| Wound healing signaling pathway | 3.22 × 10−11 | 9 | CSF2, CXCL8, FGF2, FN1, IL6, TGFA, TGFB1, TNF, VEGFA |
| Cytokine Signaling | |||
| IL17 signaling | 8.43 × 10−20 | 13 | CCL2, CCL20, CSF2, CXCL1, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, IL6, TGFB1, TNF, VEGFA |
| IL6 signaling | 2.53 × 10−5 | 4 | CXCL8, IL6, TNF, VEGFA |
| IL10 signaling | 1.23 × 10−4 | 3 | IL10, IL6, TNF |
| IL8 signaling | 1.73 × 10−4 | 4 | CXCL1, CXCL8, ICAM1, VEGFA |
| Cellular Immune Response | |||
| Role of cytokines in mediating communication between immune cells | 8.74 × 10−11 | 6 | CSF2, CXCL8, IL10, IL6, TGFB1, TNF |
| Th1 and Th2 activation pathway | 8.01 × 10−5 | 4 | ICAM1, IL10, IL6, TGFB1 |
| Th1 pathway | 5.81 × 10−4 | 3 | ICAM1, IL10, IL6 |
| Th2 pathway | 8.13 × 10−4 | 3 | ICAM1, IL10, TGFB1 |
| Communication between innate and adaptive immune cells | 7.44 × 10−3 | 5 | CSF2, CXCL8, IL10, IL6, TNF |
| Diseases or Functions Annotations | |||
| Antimicrobial Response, Inflammatory Response | |||
| Antibacterial response | 1.66 × 10−22 | 13 | CAMP, CCL20, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, IL10, IL6, RNASE7, S100A12, S100A7, S100A8, S100A9, TNF |
| Antimicrobial Response, Inflammatory Response | |||
| Chemoattraction | 5.09 × 10−23 | 12 | CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL3, CXCL8, DEFB4A/DEFB4B, FN1, TGFB1, TNF, VEGFA |
| Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking, Inflammatory Response | |||
| Chemotaxis | 4.28 × 10−37 | 27 | CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, FGF2, FN1, ICAM1, IL10, IL6, S100A12, S100A7, S100A8, S100A9, SELE, SMAD3, SMAD4, TGFA, TGFB1, TNF, VEGFA |
| Chemotaxis of leukocytes | 1.43 × 10−35 | 24 | CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, FN1, ICAM1, IL10, IL6, S100A12, S100A7, S100A8, S100A9, SELE, SMAD3, TGFB1, TNF, VEGFA |
| Inflammatory Response | |||
| Inflammatory response | 9.34 × 10−29 | 26 | CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, FGF1, FGF2, FN1, ICAM1, IL10, IL6, S100A12, S100A7, S100A8, S100A9, SELE, SMAD3, TGFB1, TNF, VEGFA |
| Proinflammatory response | 4.92 × 10−15 | 7 | CCL2, CXCL3, CXCL8, IL10, IL6, TNF, VEGFA |
| Innate immune response | 5.94 × 10−14 | 10 | CAMP, CXCL1, CXCL8, FN1, IL10, IL6, RNASE7, S100A12, SMAD3, TNF |
| Tissue Development | |||
| Healing of wound | 1.53 × 10−20 | 13 | CSF2, FGF1, FGF2, FN1, ICAM1, IL10, IL6, SMAD3, SMAD4, TGFA, TGFB1, TNF, VEGFA |
| Cell-To-Cell Signaling and Interaction, Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking, Inflammatory Response | |||
| Cell movement of monocytes | 1.37 × 10−31 | 19 | CAMP, CCL2, CCL20, CSF2, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, FN1, ICAM1, IL10, IL6, S100A12, S100A7, SELE, SMAD3, TGFB1, TNF, VEGFA |
| Cell movement of neutrophils | 2.01 × 10−28 | 21 | CAMP, CCL2, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB1, DEFB103A/DEFB103B, DEFB4A/DEFB4B, FN1, ICAM1, IL10, IL6, S100A12, S100A8, S100A9, SELE, SMAD3, TGFB1, TNF |
| Cell-To-Cell Signaling and Interaction, Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking, Inflammatory Response | |||
| Recruitment of cells | 7.85 × 10−29 | 21 | BMP10, CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB4A/DEFB4B, FGF2, FN1, ICAM1, IL10, IL6, S100A8, SELE, SMAD3, TGFB1, TNF, VEGFA |
| Recruitment of leukocytes | 1.05 × 10−25 | 19 | BMP10, CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB4A/DEFB4B, FN1, ICAM1, IL10, IL6, S100A8, SELE, SMAD3, TGFB1, TNF |
| Cell-To-Cell Signaling and Interaction, Inflammatory Response | |||
| Immune response of cells | 2.70 × 10−18 | 18 | CAMP, CCL2, CCL20, CSF2, CXCL1, CXCL3, CXCL8, FN1, ICAM1, IL10, IL6, S100A12, S100A8, S100A9, SMAD3, TGFB1, TNF, VEGFA |
| Immune response of myeloid cells | 2.85 × 10−17 | 13 | CAMP, CCL2, CSF2, CXCL1, CXCL3, CXCL8, FN1, ICAM1, IL10, IL6, S100A9, TGFB1, TNF |
| Cellular Growth and Proliferation | |||
| Angiogenesis | 1.74 × 10−23 | 24 | BMP10, CAMP, CCL2, CSF2, CXCL1, CXCL2, CXCL8, FGF1, FGF2, FN1, ICAM1, IL10, IL6, PIGF, S100A12, S100A8, S100A9, SELE, SMAD3, SMAD4, TGFA, TGFB1, TNF, VEGFA |
| Proliferation of vascular cells | 3.32 × 10−20 | 16 | CAMP, CCL2, CXCL1, CXCL8, FGF1, FGF2, FN1, IL10, IL6, S100A8, S100A9, SMAD3, SMAD4, TGFB1, TNF, VEGFA |
| Cellular Movement, Hematological System Development and Function, Immune Cell Trafficking | |||
| Cell survival | 1.73 × 10−17 | 24 | CAMP, CCL2, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, DEFB103A/DEFB103B, DEFB4A/DEFB4B, FGF1, FGF2, FN1, ICAM1, IL10, IL6, S100A8, S100A9, SELE, SMAD3, SMAD4, TGFA, TGFB1, TNF, VEGFA |
| Cell viability | 2.74 × 10−15 | 22 | CAMP, CCL2, CSF2, CXCL1, CXCL2, CXCL3, CXCL8, FGF1, FGF2, FN1, ICAM1, IL10, IL6, S100A8, S100A9, SELE, SMAD3, SMAD4, TGFA, TGFB1, TNF, VEGFA |