Abstract

Colorectal cancer (CRC) is the third most common malignancy worldwide, with an estimated one million new cases and half million deaths yearly. Screening for CRC allows early stage diagnosis of malignancy and potentially reduces disease mortality. The convenient and inexpensive fecal occult blood test (FOBT) screening test has low sensitivity and requires dietary restriction, which impedes compliance. Although colonoscopy. Is the golden screening standard for the for this cancer, the invasive nature, abdominal pain and high cost have hampered worldwide application of this procedure. A noninvasive sensitive screen for colon cancer (CC) requiring no dietary restriction is a more convenient test. CC is more abundant in the USA than rectal cancer (RC). The discovery of small non-coding protein sequences, 17- 27 nucleotides long RNAs (such as microRNAs), has opened new opportunities for a non-invasive test for early diagnosis of many cancers. MiRNA functions seem to regulate development and apoptosis, and specific miRNAs are critical in oncogenesis, effective in classifying solid and liquid tumors, and serve as oncogenes or suppressor genes. MiRNA genes are frequently located at fragile sites, as well as minimal regions of loss of heterozygosity, or amplification of common break-point regions, suggesting their involvement in carcinogenesis. Profiles of miRNA expression differ between normal tissues and tumor types, and evidence suggests that miRNA expression profiles can cluster similar tumor types together more accurately than expression profiles of protein-coding mRNA genes. Although exosomal RNA are missed, a parallel carried out on stool miRNAs to compare the extent of loss when colonocytes are only used can be carried out, and an appropriate corrections for exsosomal loss can be made. To ascertain the validity of a miRNA screening test for CC, it must be validated in a study, using a nested case control epidemiology design and employing a prospective specimen collection, retrospective blind evaluation (PRoBE) of control subjects and test colon cancer patients, as delineated by NCI’s Early Detection Research Network (EDRN) http://edrn.nci. nih.gov. Immunoparamagnetic are employed to capture colonocytes from harsh stool environment, whose extracted fragile total small RNA is stabilized shortly after stool excretion by commercial kits so it does not ever fragment, followed by standardized analytical quantitative miRNA dPCR-chip profiling in noninvasive stool samples, to develop a panel of few stable miRNAs for absolute quantitative diagnostic screening of early sporadic colon cancer (stage 0-1), more economically and with higher sensitivity and specificity than other CC screening test on the market today.

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