title: Vascular endothelial growth factor receptors 1,3 and caveolin-1 are implicated in colorectal cancer aggressiveness and prognosis--correlations with epidermal growth factor receptor, CD44v6, focal adhesion kinase, and c-Met.
abstract: Vascular endothelial growth factor receptor-1 (VEGFR-1) and caveolin-1 have been shown to act both as tumor-promoting and tumor-suppressing proteins in various malignancies as well as in colorectal cancer (CRC), while VEGFR-3's lymphagiogenic involvement and connection to tumor parameters has yielded heterogenic results. This study was designed to investigate the expression of these molecules in 183 human CRC tissue specimens and explore their effect in both clinicopathological parameters and disease prognosis. We also utilize our previous results regarding epidermal growth factor receptor (EGFR), c-Met, CD44v6, and focal adhesion kinase, in an attempt to further clarify their distinct role in tumor prognosis and their crosstalk. Caveolin-1 was more freely distributed in the neoplasms of the right colon and restricted towards the left and the rectal cancer samples (p = 0.022); VEGFR-3 was associated with higher nodal metastasis' status (p = 0.001) and staging (p = 0.006), and loss of VEGFR-1 predicted distant metastasis (p = 0.026) and advanced stage (p = 0.049). Prompted by previous reports, we performed all analyses also in the patient group of early (I and II) tumor stage where it was evident that VEGFR-1 was more frequently expressed in patients under 60 years old (p = 0.014) and VEGFR-3 was significantly elevated in left colon cancers (p = 0.039) and female patients (p = 0.038). Within the advanced stage (III and IV), the absence of VEGFR-1 exhibited a tendency for higher M status (p = 0.067) and lack of caveolin-1 signified worse AJCC classification (p = 0.053). Additionally, patient survival was influenced from VEGFR-3 (p = 0.019) for the whole sample, whereas subgroup analyses provided a correlation between caveolin-1 expression and improved survival in the early detection group of patients (p = 0.022). Using Cox regression for all available markers, FAK, CD44v6, and Caveolin-1 [corrected] emerged in this study as potential surrogate markers, the latter having positive prognostic significance. We further explored the multiple receptor correlations that were identified.
authors.affiliation: Department of General Medicine, G. Gennimatas General Hospital, Athens, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Garouniatis
authors.forename: Adamantia
authors.initials: A
authors.lastname: Zizi-Sermpetzoglou
authors.forename: Spyros
authors.initials: S
authors.lastname: Rizos
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Kostakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikiteas
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; C112697:CD44v6 antigen; D051242:Caveolin 1; D018960:Hyaluronan Receptors; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human