title: Circulating microRNA expressions in colorectal cancer as predictors of response to chemotherapy.
abstract: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the third leading cause of cancer death in the Western world. Chemotherapy has been shown to improve outcomes in patients with CRC; however, only selected patients would benefit from this treatment. We aimed to identify predictors of response to chemotherapy in CRC using circulating microRNAs (miRNAs). We studied differential miRNA expression by miRNA array from serum of 253 patients who had chemotherapy treatment. We screened the differentially expressed serum miRNAs with TaqMan low-density arrays using pooled CRC patient serum samples. Differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription PCR in individual samples. We performed additional unsupervised cluster to analyse the differential expression of serum miRNA between the chemosensitive and chemoresistant patients. A distinct miRNA expression signature in response to chemotherapy was identified. The TaqMan low-density array results demonstrated that 17 serum miRNAs could predict chemosensitivity and chemoresistance. The quantitative reverse transcription PCR analysis further identified a profile of five serum miRNAs (miR-20a, miR-130, miR-145, miR-216 and miR-372) as a biomarker for predicting the chemosensitivity of CRC. The areas under the receiver operating characteristic curve of this five-serum miRNA signature were 0.841 and 0.918 for the two sets of serum samples, respectively. We identified a group of miRNA predictors in response to chemosensitivity for CRC patients. This could lead to a significant improvement in chemotherapy regimen selection strategy and personalized CRC management.
authors.affiliation: Department of Surgery, Affiliated Hospital of Medical College Qingdao University, Qingdao, Shandong Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhang
authors.forename: Meisheng
authors.initials: M
authors.lastname: Bi
authors.forename: Xuelong
authors.initials: X
authors.lastname: Jiao
authors.forename: Dianliang
authors.initials: D
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077150:Oxaliplatin; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin