Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians

Abstract

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.

Biomarkers of Inflammatory Bowel Disease

“…The combination of cytology and the miRNA signature had a positive predictive value > 99% (76). MiRNA biomarker discovery studies have also been performed using fecal samples for the screening of colon cancer (77, 78) and pancreatic cancer (79). Together, these studies show that the use of protein and/or miRNA panels can improve the predictive values of the current procedures and out-perform the use of a single biomarker for classifying disease types, giving a prognosis or diagnosis, and predicting the therapeutic response.…”

MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis

“…4, 5 Many miRNAs were found to be aberrantly expressed in colorectal cancer (CRC) with the downregulation of miR-601, miR-192, miR-345, miR-215, and miR-612, and the upregulation of miR-223, miR-18a, miR-155, miR-31, and miR-224, when compared with those found in normal colon mucosa. 6, 7, 8, 9 Given their involvement in the initiation, progression, and metastasis of human cancers, some of these miRNAs have become studies of great interest. For example, it has been shown that levels of miR-143 and miR-145 tend to be lower in CRC tissue than in normal tissue.…”

The expression and clinical significance of microRNAs in colorectal cancer detecting

“…MiR-223 Fig. 4 Forest plots of multivariable meta-regression analyses for sensitivity and specificity and miR-451, measured in the feces samples, appear to have an aberrant expression profile between the CRC patients and healthy people [39]. The significant difference of expression level was also discovered in miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203.…”

“…After the full-texts review, another 43 studies were excluded, including 14 studies irrelevant to diagnosis, 19 studies without sufficient data, 5 studies about metastatic disease, and other 5 studies with duplicate data. Finally, 29 eligible articles were included in our metaanalysis, including 19 articles about blood-based miRNAs assays [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], and 10 articles about feces-based miRNAs assays [3,5,[32][33][34][35][36][37][38][39].…”