title: Effects of preanalytic variables on circulating microRNAs in whole blood.
abstract: Research in the last decade suggests the clinical potential of circulating microRNAs in whole blood as biomarkers for cancer detection. However, before applying the identified circulating microRNAs clinically, biospecimen-focused research has to be performed to identify possible preanalytic variables that may significantly affect the levels of circulating microRNAs. In this study, using a unique resource of the Data Bank and BioRepository (DBBR) at Roswell Park Cancer Institute, we conducted a two-step analysis to identify internal control circulating microRNAs in whole blood and then to study how selected major preanalytic variables (namely, processing delay, storage condition, storage time, and freeze/thaw cycles) might affect the detection of circulating microRNAs. In the discovery phase of the first step, we identified three microRNAs, including miR346, miR134, and miR934, whose levels exhibited the smallest variation between the case-control groups, as well as within each group interindividually. In the further validation analysis, the consistency was validated for miR346 and miR134 but not for miR934. At the second step, using miR346 and miR134 as internal controls, we observed that as the numbers of freeze/thaw cycles increased, levels of both miR346 and miR134 were significantly decreased (Ptrend < 0.0001); varying other processing and storage conditions did not affect miRNA levels. In the paralleled analysis in plasma samples, levels of miR16 were significantly decreased by increasing processing delay and increasing numbers of freeze/thaw cycles but not affected by storage condition and duration. The results from this study highlight the necessity of biospecimen-focused research on circulating microRNAs before clinical utilization. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."
authors.affiliation: Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, Texas. hzhao2@mdanderson.org song.liu@roswellpark.org christine.ambrosone@roswellpark.org.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York. School of Basic Medicine, Peking Union Medical College, Beijing, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Medico
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Maochun
authors.initials: M
authors.lastname: Qin
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Mary
authors.initials: M
authors.lastname: Nesline
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York. hzhao2@mdanderson.org song.liu@roswellpark.org christine.ambrosone@roswellpark.org.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York. hzhao2@mdanderson.org song.liu@roswellpark.org christine.ambrosone@roswellpark.org.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs