Abstract
Genes involved in the angiogenic process have been proposed for the diagnosis and therapeutic response of metastatic colorectal cancer (CRC). This study aimed to investigate the value of PTGS2, JAG1, GUCY2C and PGF-circulating RNA as biomarkers in metastatic CRC. Blood cells and serum mRNA from 59 patients with metastatic CRC and 47 healthy controls were analyzed by digital PCR. The area under the receiver operating characteristic curve (AUC) was used to estimate the diagnostic value of each mRNA alone or mRNA combinations. A significant upregulation of the JAG1, PTGS2 and GUCY2C genes in blood cells and serum samples from metastatic CRC patients was detected. Circulating mRNA levels in the serum of all genes were significantly more abundant than in blood. The highest discrimination ability between metastatic CRC patients and healthy donors was obtained with PTGS2 (AUC of 0.984) and GUCY2C (AUC of 0.896) in serum samples. Biomarker combinations did not improve the discriminatory capacity of biomarkers separately. Analyzed biomarkers showed no correlation with overall survival or progression-free survival, but GUCY2C and GUCY2C/PTGS2 expression in serum correlated significantly with the response to antiangiogenic agents. These findings demonstrate that assessment of genes involved in the angiogenic process may be a potential non-invasive diagnostic tool for metastatic CRC and its response to antiangiogenic therapy.
Highlights
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide with an incidence that is on track to increase from 1.8 million new cases in 2018 to 2.5 million in 2035
The aim of this study was to assess the utility of five angiogenesis-related genes as biomarkers for predicting prognosis and response to different chemotherapy regimens combined with bevacizumab
Our results showed that circulating mRNA levels in the serum ples,ofthe expression of each individual gene obtained in both fluids all genes were significantly more abundant than in blood by cellsdPCR
Summary
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide with an incidence that is on track to increase from 1.8 million new cases in 2018 to 2.5 million in 2035. The prognosis of metastatic CRC has improved in recent decades with the use of new treatment strategies, new biological agents and therapy optimization based on the genomic characteristics of the tumor. RAS, BRAF and microsatellite instability (MSI) determination as well as some clinical biomarkers such as primary tumor location are essential to properly select patients who are candidates for biological treatments. In spite of these advances, the 5-year overall survival of these patients with advanced disease is still less than 15% [4,5].
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