Fecal MicroRNAs as Novel Biomarkers for Colon Cancer Screening

Abstract

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, but currently available noninvasive screening programs have achieved only a modest decrease in mortality. MicroRNAs (miRNA) play an important role in a wide array of biological processes and are commonly dysregulated in neoplasia. We aimed to evaluate the feasibility of fecal miRNAs as biomarkers for colorectal neoplasia screening.Materials and Methods: Total RNA was extracted from freshly collected stool samples from 8 healthy volunteers and 29 samples collected via fecal occult blood testing from subjects with normal colonoscopies, colon adenomas, and CRCs. miRNA expression analyses were done with TaqMan quantitative reverse transcription-PCR for a subset of miRNAs. Illumina miRNA microarray profiling was done to evaluate the differences in expression patterns between normal colonic mucosa tissues and stool samples from healthy subjects.Results: We efficiently extracted miRNAs from stool specimens using our developed protocol. Data from independent experiments showed high reproducibility for miRNA extraction and expression. miRNA expression patterns were similar in stool specimens among healthy volunteers, and reproducible in stool samples that were collected serially in time from the same individuals. miRNA expression profiles from 29 patients showed higher expression of miR-21 and miR-106a in patients with adenomas and CRCs compared with individuals free of colorectal neoplasia.Conclusion: Our data indicate that miRNAs could be extracted from stool easily and reproducibly. The stools of patients with colorectal neoplasms have unique and identifiable patterns of miRNA expression.Impact: Fecal miRNAs may be an excellent candidate for the development of a noninvasive screening test for colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 19(7); 1766-74. ©2010 AACR.

Advances in epigenetic biomarker research in colorectal cancer

“…In addition, miR-144* and miR-106a were found to be significantly overexpressed in adenomas and in the stool of CRC patients compared with healthy individuals [86,89] . These studies have confirmed that miRNAs from stool samples require validation as diagnostic biomarkers for CRC.…”

MicroRNAs: Biogenesis, Roles for Carcinogenesis and as Potential Biomarkers for Cancer Diagnosis and Prognosis

“…Nevertheless, each of the approaches has its own specific advantages and disadvantages. Recently, the findings of miRNAs in body fluids, such as serum, urine and colostrum (Hanke et al, 2010;Link et al, 2010) have strengthened investigations into the use of miRNAs as non-invasive biomarkers of disease and a therapeutic response in a range of cancers including lung cancer, ovarian cancer, colorectal cancer, renal cancer, glioblastoma, prostate cancer and breast cancer (Cortez et al, 2012). In recent times, Lin et al (2014) characterized miRNAs expression profiles in cervical cancer of Uygur women to identify the biomarkers for early diagnosis.…”

MicroRNAs as molecular markers for colon cancer Diagnostic screening in stool & blood

“…On the other hand, our data and others [25,27,28,[54][55][56][57][58][59][60][61][62][63][64][65][66] have shown that quantitative changes in the expression of few miRNA genes in stool or blood that are associated with colon cancer permit development of more sensitive and specific CRC molecular markers than those currently available on the market. In comparison to the commonly employed FOBT stool test, a noninvasive molecular and reliable test would particularly be more convenient as there would be no requirement for dietary restriction, or meticulous collection of samples, and thus a screening test would be acceptable to a broader segment of the population.…”

“…In comparison to the commonly employed FOBT stool test, a noninvasive molecular and reliable test would particularly be more convenient as there would be no requirement for dietary restriction, or meticulous collection of samples, and thus a screening test would be acceptable to a broader segment of the population. Using stable molecules such as miRNAs that are not easily degradable when extracted from stool or blood and manipulated thereafter, a miRNA -approach for colon cancer is thus preferable to a transcriptomic mRNA-, mutation DNA-, epigeneticor a proteomic-based test [25,27,[55][56][57][58][59][60][61][62][63][64][65][66][67][68], particularly that we and others have shown that these stable, nondegradable miRNA molecules can be easily extracted from stool or from circulation in vitro using commercially available kits. Advantages and disadvantages of the in vivo and in vitro tests are presented in table 1.…”