Abstract
Colorectal cancer (CRC) is the third most common cancer in the world. A significant survival rate is achieved if it is detected at an early stage. A whole blood screening test, without any attempt to isolate blood fractions, could be an important tool to improve early detection of colorectal cancer. We searched for candidate markers with a novel approach based on the Transcriptome Mapper (TRAM), aimed at identifying specific RNAs with the highest differential expression ratio between colorectal cancer tissue and normal blood samples. This tool permits a large-scale systematic meta-analysis of all available data obtained by microarray experiments. The targeting of RNA took into consideration that tumour phenotypic variation is associated with changes in the mRNA levels of genes regulating or affecting this variation.A real time quantitative reverse transcription polymerase chain reaction (qRT- PCR) was applied to the validation of candidate markers in the blood of 67 patients and 67 healthy controls. The expression of genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 resulted as being statistically different.In particular ROC curves attested for TSPAN8 an AUC of 0.751 with a sensitivity of 83.6% and a specificity of 58.2% at a cut off of 10.85, while the panel of the two best genes showed an AUC of 0.861 and a sensitivity of 92.5% with a specificity of 67.2%.Our preliminary study on a total of 134 subjects showed promising results for a blood screening test to be validated in a larger cohort with the staging stratification and in patients with other gastrointestinal diseases.
Highlights
Colorectal cancer (CRC) is the third most common cancer in the world, with nearly 1.4 million new cases detected in 2012
A systematic meta-analysis of differential gene expression in CRC and normal blood was conducted to identify the mRNAs with the highest expression ratio between CRC and blood, in order to select the best candidate biomarkers
We searched for the candidate markers with the Transcriptome Mapper (TRAM) software application, which executed the basic computational biology tasks needed for this study
Summary
Colorectal cancer (CRC) is the third most common cancer in the world, with nearly 1.4 million new cases detected in 2012. A significant survival rate is achieved if the primary tumour is detected at an early stage [1,2,3]. Most CRC develops in a multistep process, starting with benign precancerous adenomas, which develop into aggressive metastatic carcinoma [4]. This makes early detection crucial to benefit the chances of a positive outcome for CRC patients [5]. Multiple non-invasive screening modalities have been investigated including faecal tests that detect the presence of haemoglobin or blood in the stools [5,6,7], and improved faecal test methods that add an integral DNA extraction [8]. Imperiale at al. [9] proposed a multi-target stool DNA test, Cologuard (Exact Sciences Corporation, Madison WI), approved by the www.impactjournals.com/oncotarget
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