Table 1.
List of candidate genes and proteins of interest related to angiogenesis and endothelial-cell markers as prognostic indicators in cervical carcinoma
| Molecular target (gene/protein/biomarker) |
Pathologic and/or prognostic significance in Invasive Cervical Cancer (ICC) |
|---|---|
| Adrenomedullin (ADM) | Progangiogenic peptide upregulated in ICC, target of miR-126 |
| CD31 | Endothelial marker associated with MVD in ICC and prognostic for PFS/OS [10] |
| CD40 | Endothelial marker overexpressed with HPV 16/18+ ICC, associated with lymphatic metastasis and neovascularization [12] |
| Chintase 3 like 1(CHI3L1) | Overexpression of secreted glycoprotein correlates with prognosis and metastatsis in ICC [32] |
| Colony stimulating factor receptor (c-fms) | Proto-oncogene present in majority of ICC and absent in normal cervix, stimulates VEGF-mediated angiogenesis and involved in carcinogenesis [15] |
| Cyclooxygenase (COX- 2) | COX2 inhibition attenuated VEFG-C expression, potent mediator of lymphangiogenesis [33] |
| Endoglin (CD105) | Angiogenesis marker, highest in peritumoral areas and correlated with VEGF and EGFR overexpression [34] |
| Fibulin-4 | Glycoprotein upregulated in ICC, promotes angiogenesis and associated with poor clincopathologic characteristics [35] |
| Maspin | Tumor suppressor implicated in lymphangiogenesis and metastasis [13] |
| miR-126 | Micro RNA involved in angiogenesis and vascular integrity, down regulated [36] |
| Tc17 (cytotoxic T cells+IL17) | Infiltration by IL 17 producing T-cells in ICC correlated with lymph node metastasis and MVD [37] |
| Thrombospondin (TSP1) | Anti-angiogenesis factor that may regulate the angiogenic switch between CIN & ICC, mixed data on prognostic significance [10, 38, 39] |
| Tissue factor pathway inhibitor (TFPI2) | Serine protease inhibitor implicated in apoptosis, angiogenesis and progression of ICC [40] |
| Transforming growth factor β1 (TGFβ1) | Prognostic marker, strong expression associated with worse survival in CD105+ tumors [11] |
| Vasohibin | Angiogenesis inhibitor and potential marker, endothelial cell expression correlated with VEGFR-2 in ICC [41] |
Abbreviations: CIN, cervical intraepithelial neoplasia; COX, cyclooxygenase; HPV, human papillomavirus; ICC, invasive cervical cancer; IL, interleukin; MVD, microvessel density; OS, overall survival; PFS, progression free survival; TFPI, Tissue factor pathway inhibitor TSP, thrombospondin; VEGFR, vascular endothelial growth factor receptor.