Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection

Maria Teresa Rodia, Giampaolo Ugolini, Gabriella Mattei, Isacco Montroni, Davide Zattoni, Federico Ghignone, Giacomo Veronese, Giorgia Marisi, Mattia Lauriola, Pierluigi Strippoli, Rossella Solmi, Maria Teresa Rodia, Giampaolo Ugolini, Gabriella Mattei, Isacco Montroni, Davide Zattoni, Federico Ghignone, Giacomo Veronese, Giorgia Marisi, Mattia Lauriola, Pierluigi Strippoli, Rossella Solmi

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.

Keywords: CRC: colorectal cancer; CTC: circulating tumour cells; TRAM: Transcriptome Mapper.

Conflict of interest statement

Authors declare no competing interest. All authors have read the journal's authorship agreement and the manuscript has been reviewed and approved by all named authors.

Figures

Figure 1. ROC curves of TSPAN8, LGALS4,…
Figure 1. ROC curves of TSPAN8, LGALS4, COL1A2 and CEACAM6
Figure 2. ROC curves of panels of…
Figure 2. ROC curves of panels of the indicated marker gene combinations
(A) TSPAN8 + COL1A2; (B) TSPAN8 + LGALS4; (C) TSPAN8+COL1A2+LGALS4.

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