Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians.
Fecal microRNAs (miRNAs) are increasingly explored as non-invasive markers of colorectal cancer (CRC). However, its holistic profile in Asian CRC patients remains elusive. In the present study, the global human fecal miRNAs in Asian Chinese CRC patients was assayed to elucidate novel diagnostic fecal markers. Additionally, the influence of blood in stool on fecal miRNA levels was investigated for the first time. Microarray analysis was applied to profile the fecal miRNAs extracted from CRC patients and healthy subjects. Concurrently, surgically resected tumor and matched normal mucosae were analyzed. Potential fecal miRNA markers were further confirmed using real-time PCR in 17 CRC patients and 28 healthy subjects. Global miRNA profiling uncovered 17 fecal markers (p<0.05) differentially regulated in CRC. Fecal miR-223 and miR-451 represented robust markers in distinguishing CRC patients from healthy subjects, as evident from areas under the receiver operator characteristic curves of 0.939 and 0.971, respectively. Blood in stool affected fecal miR-451, miR-223 and miR-135b levels to a varying extent and substantially impacted the interpretation of the clinical data. Notably, a discrete set of aberrant miRNAs occurred within the tumor, indicating the presence of contributors beyond the exfoliation of tumor cells to the fecal miRNA profile. In summary, the utility of a global miRNA screening approach was successfully demonstrated in elucidating diagnostic markers of CRC. In particular, fecal miR-223 and miR-451 hold promise in detecting CRC.
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
Lee Cheng
LC
Phua
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
Xiu Ping
XP
Chue
Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore.
Poh Koon
PK
Koh
Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore.
Peh Yean
PY
Cheah
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
Eric Chun Yong
EC
Chan
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
Han Kiat
HK
Ho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005243:Feces; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D035683:MicroRNAs