Table 1.
Expression of tumor biomarkers in keloids.
| Biomarker | Normal physiological function | Associated tumor processes | Expression in keloids | References |
|---|---|---|---|---|
| Bcl-2 | Apoptosis regulation | Dysregulated in skin cancers and upregulated in some chondrosarcomas | Positive in basal keratinocytes and spindle-shaped cells | (79–82) |
| BMP2 | TGF-β family | Highly expressed in malignant fibrous histiocytoma | ↑ | (31, 83) |
| c-jun | Role in organogenesis | Proto-oncogene which promotes cell migration and motility factor ENPP2 in soft tissue sarcomas and is strongly expressed in BCC | Expressed in keloid keratinocytes but absent in resting keloids | (82, 84–86) |
| CXCR4 | Increases fibroblastic expression of collagen and TGF-β | Cross-talk between tumor cells and tumor micro-environment | Positive | (87, 88) |
| HIF-1 | Response to hypoxia | Adaptation of tumor cells to hypoxia | ↑ | (89, 90) |
| HSP27 | Stress response protein | Highly expressed in cancers | ↑ | (91–93) |
| HSP47 | Collagen maturation | Promotes cell survival in various mesenchymal tumors | ↑ | (94–96) |
| HSP90 | Indicates cellular replicative potential | ↑ | (97, 98) | |
| IL-6 | Interleukin with pro- and anti-inflammatory roles | Pro-tumorigenic | ↑ | (39, 99, 100) |
| SERPINB5 | P53-regulated tumor suppressor | Expressed in various cancers | Positive | (101–103) |
| MMP-2, MMP-9 | ECM degradation | Expressed in various cancers | ↑ | (53, 104–108) |
| MRF 15 | Cell senescence | Senescence induction of human tumor cell lines | ↑ in keloid fibroblasts | (23, 109) |
| mTOR | Cell signaling mediator | Dysregulated in various cancers | ↑ | (55, 110) |
| Nanog | ESC marker | Multifaceted role in cancers, positive in bone sarcomas | ↑ in KPCs, KALT | (39, 111–113) |
| NIP3 | Pro-apoptotic, induced in response to hypoxia | Expressed in various tumors | ↓ | (114–116) |
| Notch | Cell-to-cell signaling | Dual role in tumor mediation as promoter and suppressor | ↑ | (117, 118) |
| Oct4 | ESC marker | Regulates EMT and ERK1/2 signaling in ovarian cancer, positive in bone sarcomas | ↑ in KPCs, KALT | (39, 112, 113, 119) |
| Osteopontin | Regulation of cellular functions | Promotes invasiveness in various carcinomas | Expressed in epidermis | (120, 121) |
| p53 | Tumor suppressor gene | Mutated in more than 50% of all tumors | ↑ in central region of KFs | (122, 123) |
| p63 | Inhibits p53 translational activation | Expressed in many benign giant cell bone tumors and uncommon in malignant tumors | ↑ | (124–126) |
| PDGF | Protein tyrosine kinase (PTK) | Mutated in some cancers | Positive | (99, 100, 127) |
| Periostin | Collagen fibrillogenesis | Tumor progression and metastasis | ↑ | (31, 128, 129) |
| ROS | Apoptosis induction in DNA damage | Second messenger in intracellular signaling in cancer | ↑ | (130, 131) |
| S100 | Upregulated in skin tumors | Elevated in osteosarcoma | Variable expression | (132, 133) |
| Sox2 | ESC marker | Tumor initiation and maintenance of CSCs in osteosarcomas and squamous cell carcinomas | ↑ | (112, 134, 135) |
| Sox9 | Master regulator of chondrogenesis | Present in classic and mesenchymal chondrosarcoma | ↑ | (31, 63, 136) |
| STAT3 | ESC marker and oncogene activated by PDGF and IL-6 | Activated in various cancers and tumor cell lines | Expressed in endothelium of KALT microvessels | (112, 137–139) |
| Wnt10α | Anti-apoptosis | Promotes carcinogenesis | ↑ | (140–142) |