Publication: Circulating PTGS2, JAG1, GUCY2C and PGF mRNA in Peripheral Blood and Serum as Potential Biomarkers for Patients with Metastatic Colon Cancer
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Date
2021-05-22
Authors
Jimenez-Luna, Cristina
González-Flores, Encarnación
Ortiz, Raul
Martínez-González, Luis J.
Antúnez-Rodríguez, Alba
Expósito-Ruiz, Manuela
Melguizo, Consolación
Caba, Octavio
Prados, Jose
Advisors
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MDPI
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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.
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MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases::Cyclooxygenase 2
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Angiogenesis Modulating Agents::Angiogenesis Inhibitors
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::ROC Curve
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation
Medical Subject Headings::Diseases::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Anatomy::Cells::Blood Cells
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators::Autacoids::Eicosanoids::Prostaglandins::Prostaglandins F
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Multienzyme Complexes::Prostaglandin-Endoperoxide Synthases::Cyclooxygenase 2
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Angiogenesis Modulating Agents::Angiogenesis Inhibitors
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::ROC Curve
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation
Medical Subject Headings::Diseases::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Anatomy::Cells::Blood Cells
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Inflammation Mediators::Autacoids::Eicosanoids::Prostaglandins::Prostaglandins F
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers
DeCS Terms
CIE Terms
Keywords
Metastatic colon cancer, Biomarkers, Angiogenesis, Liquid biopsy, Circulating mRNA, Digital PCR, Metástasis de la neoplasia, Neoplasias del colon, Biomarcadores, Biopsia líquida, ARN mensajero, Reacción en cadena de la polimerasa
Citation
Jimenez-Luna C, González-Flores E, Ortiz R, Martínez-González LJ, Antúnez-Rodríguez A, Expósito-Ruiz M, et al. Circulating PTGS2, JAG1, GUCY2C and PGF mRNA in Peripheral Blood and Serum as Potential Biomarkers for Patients with Metastatic Colon Cancer. J Clin Med. 2021 May 22;10(11):2248