title: Differential expression of circulating microRNAs according to severity of colorectal neoplasia.
abstract: There is a need to develop a colorectal cancer (CRC) screening test that is noninvasive, cost effective, and sensitive enough to detect preneoplastic lesions. This case-control study examined the feasibility of using circulating extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal neoplasia of various severity and hence for early detection of colorectal neoplasia. Archived serum samples of 10 normal controls and 31 cases, including 10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were profiled for circulating miRNAs using next-generation sequencing. Multiple linear regression, adjusting for age, gender, and smoking status, compared controls and the 3 case groups for levels of 175 miRNAs that met stringent criteria for miRNA sequencing analysis. Of the 175 miRNAs, 106 miRNAs were downregulated according to severity of neoplasia and showed a relative decrease in the expression from controls to nonadvanced adenoma to advanced adenoma to CRC (Ptrend < 0.05). Pairwise group comparisons showed that 39 and 80 miRNAs were differentially expressed in the advanced adenoma and CRC groups compared with the controls, respectively. Differences in miRNA levels between the nonadvanced adenoma group and controls were modest. Our study found that expression of many miRNAs in serum was inversely correlated with the severity of colorectal neoplasia, and differential miRNA profiles were apparent in preneoplastic cases with advanced lesions, suggesting circulating miRNAs could serve as potential biomarkers for CRC screening.
authors.affiliation: Albert Einstein College of Medicine, Department of Epidemiology & Population Health, Bronx, New York.
authors.forename: Gloria Y F
authors.initials: GYF
authors.lastname: Ho
authors.affiliation: Albert Einstein College of Medicine, Department of Genetics, Bronx, New York.
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: Albert Einstein College of Medicine, Department of Epidemiology & Population Health, Bronx, New York.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Albert Einstein College of Medicine, Department of Epidemiology & Population Health, Bronx, New York.
authors.forename: Juan
authors.initials: J
authors.lastname: Lin
authors.affiliation: Albert Einstein College of Medicine, Department of Obstetrics & Gynecology and Women's Health, Bronx, New York.
authors.forename: Zev
authors.initials: Z
authors.lastname: Williams
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.affiliation: Albert Einstein College of Medicine, Department of Genetics, Bronx, New York.
authors.forename: Jung Yoon
authors.initials: JY
authors.lastname: Park
authors.affiliation: Albert Einstein College of Medicine, Department of Epidemiology & Population Health, Bronx, New York.
authors.forename: Olivier
authors.initials: O
authors.lastname: Loudig
authors.affiliation: Albert Einstein College of Medicine, Department of Genetics, Bronx, New York.
authors.forename: Yousin
authors.initials: Y
authors.lastname: Suh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D044967:Serum / Q000378:metabolism
chemical_list: D035683:MicroRNAs