Year-end Sale % OFF 
Abstract
BackgroundColorectal 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.MethodsFor 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.ResultsTissue 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.ConclusionsOur 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.
Highlights
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
In order to establish the presence of genetic alterations, samples were characterized by Generation Sequencing (NGS) using a commercial targeted Next Generation Sequencing (NGS) panel of 50 genes known or highly suspected to promote various tumor types, included Colorectal cancer (CRC) (Fig. 1a and Supplementary Table S2)
A detailed data analysis evidenced that the most common mutations concerned APC, TP53, KRAS, PI3KCa and KDR (Fig. 1a). Among these 5 genes, APC, TP53, KRAS and PI3KCa are relevant in the tumorigenesis of CRC, whilst KDR encodes for VEGFR2, the main receptor vascular endothelial growth factor (VEGF)-A, and its mutational state could be relevant in defining the prognostic role of VEGF-A in CRC patients
Summary
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. Colorectal cancer (CRC) is considered a very important public health issue since it is the third most common cancer type diagnosed in men and the second most commonly occurring tumor in women [1]. Addition of target therapy based on the administration of antibodies against the vascular endothelial growth factor (VEGF) or the epidermal growth factor receptor (EGFR), has demonstrated to further improve the clinical outcome of metastatic CRC patients [5]. A certain number of CRC patients has demonstrated to not benefit of these therapeutic regimens [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
