Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review)

“…The 'mutator phenotype' may have various manifestations, including point mutations, CIN, MSI, CIMP and LOH (21). CIN appears to be the most common type of genetic instability in CRC, observed in 85% of adenoma-carcinoma transitions (5)(6)(7). CIN refers to a high rate of gains or losses of whole, or large portions of chromosomes.…”

“…The majority of sporadic CRCs (~85%) exhibit chromosomal instability (CIN), with changes in chromosome number and structure (5)(6)(7)(8). These changes include gains or losses of chromosomal segments, chromosomal rearrangements, and loss of heterozygosity (LOH), which results in gene copy number variations (CNVs) (5)(6)(7)(8). These alterations affect the expression of tumor-associated genes, and/or genes that regulate cell proliferation or cell cycle checkpoints, which, in turn, may activate pathways essential for CRC initiation and progression (9,10).…”

Molecular Diagnostics in Colorectal Cancer

“…The methylation of MLH1 associated silencing is widely used as prognostic and predictive markers for CRC. 15,17,24 …”

“…Apart from the miRNAs mentioned above, miR-211 is also believed to be a potential marker for the diagnosis and prognosis of CRC. 2,11,20 …”

“…Several forms of genomic instability (CIN), microsatellite instability (MSI), and epigenetic gene silencing. 2 The molecular biological markers status of CRC patients are now considered the important factors to determine either the possibility of successful treatment for CRC (predictive factor) or life expectancy (prognostic factor). Clinical applications of genomic medicine and molecular diagnostics based on testing of tumor tissues are becoming a reality in clinical practice, cancer patients.…”