Circulating molecular biomarkers for screening or early diagnosis of colorectal cancer: which is ready for prime time?

According to recent statistics, colorectal cancer (CRC) is a frequent disease, the second most frequent malignancy in women and the third most common malignant disease in men, respectively. Although reinforced emphasis on CRC screening by means of immunochemical fecal occult blood test, colonoscopy or sigmoidoscopy has contributed to decrease cancer-related deaths, alternative diagnostic tests would be needed for establishing earlier and more potentially effective treatments. Innovative diagnostic techniques have recently emerged, some of which hold promises for screening and/or early CRC detection. Recent evidence suggests that the so-called "liquid biopsy", conventionally defined as detection and quantification of circulating tumor cells (CTCs) and cancer-related nucleic acids in peripheral blood, may allow earlier diagnosis of CRC combined with lower invasiveness and less patient inconvenience, higher throughput, faster turnaround time, inferior usage of healthcare resources and relatively low cost. Encouraging data have emerged from trials based on CTCs detection, though the sensitivity of the current diagnostic techniques is still perhaps insufficient for enabling early CRC diagnosis. Among the various biomarkers that can be detected with liquid biopsy, methylation displays good diagnostic performance and relatively high cancer detection rate (between 57-64% in patients with CRC stages 0-I), which would make this test a promising tool for population screening, alone or in combination with other conventional diagnostic investigations. Encouraging evidence has also been recently published for / methylation. Regarding microRNA (miRNAs), the available evidence highlights that the combination of some of these biomarkers rather than the assessment of a single miRNA alone would enable efficient identification of early CRCs, though widespread clinical application is still challenged by a number of preanalytical, analytical and clinical issues.