TY - JOUR
T1 - TRF2 and VEGF-A
T2 - An unknown relationship with prognostic impact on survival of colorectal cancer patients
AU - Dinami, Roberto
AU - Porru, Manuela
AU - Amoreo, Carla Azzurra
AU - Sperduti, Isabella
AU - Mottolese, Marcella
AU - Buglioni, Simonetta
AU - Marinelli, Daniele
AU - Maugeri-Saccà, Marcello
AU - Sacconi, Andrea
AU - Blandino, Giovanni
AU - Leonetti, Carlo
AU - Di Rocco, Giuliana
AU - Verdina, Alessandra
AU - Spinella, Francesca
AU - Fiorentino, Francesco
AU - Ciliberto, Gennaro
AU - Biroccio, Annamaria
AU - Zizza, Pasquale
N1 - Funding Information:
This work was supported by Ministry of Health (Ricerca Corrente 2018) and by funding awarded to A.B. from Italian Association for Cancer Research IG AIRC Grant number 21579.
Publisher Copyright:
© 2020 The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/15
Y1 - 2020/6/15
N2 - Background: Colorectal cancer is one of most common tumors in developed countries and, despite improvements in treatment and diagnosis, mortality rate of patients remains high, evidencing the urgent need of novel biomarkers to properly identify colorectal cancer high-risk patients that would benefit of specific treatments. Recent works have demonstrated that the telomeric protein TRF2 is over-expressed in colorectal cancer and it promotes tumor formation and progression through extra-telomeric functions. Moreover, we and other groups evidenced, both in vitro on established cell lines and in vivo on tumor bearing mice, that TRF2 regulates the vascularization mediated by VEGF-A. In the present paper, our data evidence a tight correlation between TRF2 and VEGF-A with prognostic relevance in colorectal cancer patients. Methods: For this study we sampled 185 colorectal cancer patients surgically treated and diagnosed at the Regina Elena National Cancer Institute of Rome and investigated the association between the survival outcome and the levels of VEGF-A and TRF2. Results: Tissue microarray immunohistochemical analyses revealed that TRF2 positively correlates with VEGF-A expression in our cohort of patients. Moreover, analysis of patients' survival, confirmed in a larger dataset of patients from TCGA, demonstrated that co-expression of TRF2 and VEGF-A correlate with a poor clinical outcome in stage I-III colorectal cancer patients, regardless the mutational state of driver oncogenes. Conclusions: Our results permitted to identify the positive correlation between high levels of TRF2 and VEGF-A as a novel prognostic biomarker for identifying the subset of high-risk colorectal cancer patients that could benefit of specific therapeutic regimens.
AB - Background: Colorectal cancer is one of most common tumors in developed countries and, despite improvements in treatment and diagnosis, mortality rate of patients remains high, evidencing the urgent need of novel biomarkers to properly identify colorectal cancer high-risk patients that would benefit of specific treatments. Recent works have demonstrated that the telomeric protein TRF2 is over-expressed in colorectal cancer and it promotes tumor formation and progression through extra-telomeric functions. Moreover, we and other groups evidenced, both in vitro on established cell lines and in vivo on tumor bearing mice, that TRF2 regulates the vascularization mediated by VEGF-A. In the present paper, our data evidence a tight correlation between TRF2 and VEGF-A with prognostic relevance in colorectal cancer patients. Methods: For this study we sampled 185 colorectal cancer patients surgically treated and diagnosed at the Regina Elena National Cancer Institute of Rome and investigated the association between the survival outcome and the levels of VEGF-A and TRF2. Results: Tissue microarray immunohistochemical analyses revealed that TRF2 positively correlates with VEGF-A expression in our cohort of patients. Moreover, analysis of patients' survival, confirmed in a larger dataset of patients from TCGA, demonstrated that co-expression of TRF2 and VEGF-A correlate with a poor clinical outcome in stage I-III colorectal cancer patients, regardless the mutational state of driver oncogenes. Conclusions: Our results permitted to identify the positive correlation between high levels of TRF2 and VEGF-A as a novel prognostic biomarker for identifying the subset of high-risk colorectal cancer patients that could benefit of specific therapeutic regimens.
KW - Colorectal cancer
KW - Prognostic markers
KW - TRF2
KW - VEGF-A
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U2 - 10.1186/s13046-020-01612-z
DO - 10.1186/s13046-020-01612-z
M3 - Article
C2 - 32539869
AN - SCOPUS:85086624632
VL - 39
JO - Journal of Experimental and Clinical Cancer Research
JF - Journal of Experimental and Clinical Cancer Research
SN - 0392-9078
IS - 1
M1 - 111
ER -