TRF2 and VEGF-A: an unknown relationship with prognostic impact on survival of colorectal cancer patients.
Adenocarcinoma
/ metabolism
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ metabolism
Colorectal Neoplasms
/ metabolism
Colorectal Surgery
/ mortality
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local
/ metabolism
Prognosis
Retrospective Studies
Survival Rate
Telomeric Repeat Binding Protein 2
/ metabolism
Vascular Endothelial Growth Factor A
/ metabolism
Colorectal cancer
Prognostic markers
TRF2
VEGF-A
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
15 Jun 2020
15 Jun 2020
Historique:
received:
10
04
2020
accepted:
02
06
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
5
2
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32539869
doi: 10.1186/s13046-020-01612-z
pii: 10.1186/s13046-020-01612-z
pmc: PMC7294609
doi:
Substances chimiques
Biomarkers, Tumor
0
TERF2 protein, human
0
Telomeric Repeat Binding Protein 2
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 21579
Organisme : Ministero della Salute
ID : Ricerca corrente 2018
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