Sergio Lario1,2,3,4, Anna Brunet-Vega1,4,5, María E Quílez1,4,5, María J Ramírez-Lázaro2,3,4, Juan J Lozano3,6, Lorena García-Martínez1,2,4, Carles Pericay4,5, Mireia Miquel2,3,4, Félix Junquera2,3,4, Rafael Campo2,3,4, Xavier Calvet2,3,4,7. 1. Fundació Parc Taulí, Spain. 2. Digestive Diseases Service, Hospital de Sabadell, Sabadell, Spain. 3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. 4. Institut Universitari Parc Taulí-UAB, Sabadell, Spain. 5. Oncology Service, Hospital de Sabadell, Sabadell, Spain. 6. Bioinformatics Platform, CIBEREHD, Madrid, Spain. 7. Departament de Medicina, UAB, Sabadell, Spain.
Abstract
BACKGROUND: Helicobacter pylori infection causes long-term chronic active gastritis, a risk factor for the intestinal and diffuse forms of gastric cancer. Most gastric cancers develop in a stepwise progression from chronic active gastritis to precursor lesions of gastric cancer. The early detection of gastric cancer improves survival. Studies with recent evidence have proposed circulating-microRNAs as biomarkers of cancer. OBJECTIVE: The purpose of this study was to explore the circulating-microRNA profile from H. pylori infection to gastric adenocarcinoma. METHODS: One hundred and twenty-three patients were enrolled and assigned to the discovery or the validation sets. In the discovery phase, circulating-microRNAs were measured by dye-based quantitative polymerase chain reaction and a selection of circulating-microRNAs was validated by probe-based quantitative polymerase chain reaction. A quality control protocol was used. RESULTS: One hundred and sixty-seven circulating-microRNAs were detected. Precursor lesions of gastric cancer and gastric cancer patients showed the downregulation of eight and five circulating-microRNAs, respectively. We further validated the deregulation of miR-196a-5p in precursor lesions of gastric cancer and the deregulation of miR-134-5p, miR-144-3p and miR-451a in gastric cancer. However, circulating-microRNAs exhibited moderate diagnostic performance due to the overlap of circulating-microRNA expression between non-cancer and cancer patients. miR-144-3p/miR-451a expression levels were correlated. Interestingly, these microRNAs are in 17q11.2, a site of rearrangements associated with gastric cancer. CONCLUSION: Circulating-microRNAs are deregulated in precancerous and gastric cancer patients but efforts are needed to improve their diagnostic accuracy.
BACKGROUND: Helicobacter pylori infection causes long-term chronic active gastritis, a risk factor for the intestinal and diffuse forms of gastric cancer. Most gastric cancers develop in a stepwise progression from chronic active gastritis to precursor lesions of gastric cancer. The early detection of gastric cancer improves survival. Studies with recent evidence have proposed circulating-microRNAs as biomarkers of cancer. OBJECTIVE: The purpose of this study was to explore the circulating-microRNA profile from H. pylori infection to gastric adenocarcinoma. METHODS: One hundred and twenty-three patients were enrolled and assigned to the discovery or the validation sets. In the discovery phase, circulating-microRNAs were measured by dye-based quantitative polymerase chain reaction and a selection of circulating-microRNAs was validated by probe-based quantitative polymerase chain reaction. A quality control protocol was used. RESULTS: One hundred and sixty-seven circulating-microRNAs were detected. Precursor lesions of gastric cancer and gastric cancer patients showed the downregulation of eight and five circulating-microRNAs, respectively. We further validated the deregulation of miR-196a-5p in precursor lesions of gastric cancer and the deregulation of miR-134-5p, miR-144-3p and miR-451a in gastric cancer. However, circulating-microRNAs exhibited moderate diagnostic performance due to the overlap of circulating-microRNA expression between non-cancer and cancer patients. miR-144-3p/miR-451a expression levels were correlated. Interestingly, these microRNAs are in 17q11.2, a site of rearrangements associated with gastric cancer. CONCLUSION: Circulating-microRNAs are deregulated in precancerous and gastric cancer patients but efforts are needed to improve their diagnostic accuracy.
Authors: Benjamin Meder; Christina Backes; Jan Haas; Petra Leidinger; Cord Stähler; Thomas Großmann; Britta Vogel; Karen Frese; Evangelos Giannitsis; Hugo A Katus; Eckart Meese; Andreas Keller Journal: Clin Chem Date: 2014-06-30 Impact factor: 8.327
Authors: Catharine M Sturgeon; Michael J Duffy; Barry R Hofmann; Rolf Lamerz; Herbert A Fritsche; Katja Gaarenstroom; Johannes Bonfrer; Thorsten H Ecke; H Barton Grossman; Peter Hayes; Ralf-Thorsten Hoffmann; Seth P Lerner; Florian Löhe; Johanna Louhimo; Ihor Sawczuk; Kazuhisa Taketa; Eleftherios P Diamandis Journal: Clin Chem Date: 2010-03-05 Impact factor: 8.327
Authors: M Tsujiura; D Ichikawa; S Komatsu; A Shiozaki; H Takeshita; T Kosuga; H Konishi; R Morimura; K Deguchi; H Fujiwara; K Okamoto; E Otsuji Journal: Br J Cancer Date: 2010-03-16 Impact factor: 7.640