Improved Stool DNA Integrity Method for Early Colorectal Cancer Diagnosis

Rengucci, Claudia; Maio, Giulia De; Menghi, Maura; Scarpi, Emanuela; Guglielmo, Simona; Fusaroli, Pietro; Caletti, Giancarlo; Saragoni, Luca; Casadei-Gardini, Andrea; Zoli, Wainer; Falcini, Fabio; Amadori, Dino; Calistri, Daniele

doi:10.1158/1055-9965.epi-14-0379

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…The combination of TSPAN8 and LGALS4 shows promising values of sensitivity (92.5%) and specificity (67.16%), competing with the widely used faecal occult blood test (FOBT), or the faecal immunochemical test (FIT) (74% and 95%) and Cologuard (92% and 87%) [ 8 , 41 ]. To our knowledge, this is the first report examining TSPAN8 mRNA expression in the blood for CRC diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

“…Multiple non-invasive screening modalities have been investigated including faecal tests that detect the presence of haemoglobin or blood in the stools [ 5 – 7 ], and improved faecal test methods that add an integral DNA extraction [ 8 ]. Very recently, Imperiale at al.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Two studies 34 , 35 suggested that fluorescence long DNA (FL-DNA) might be a suitable tool for risk stratification: they indicated that coincidence of high FL-DNA values and a positive FIT corresponds to a strong increase in the probability of having CRC, whereas a low FL-DNA and a negative FIT together indicate a lower CRC risk than a negative FIT alone.…”

Section: Discussionmentioning

confidence: 99%

Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review

Niedermaier

Weigl

Hoffmeister

et al. 2016

Clinical and Translational Gastroenterology

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OBJECTIVES:Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors.METHODS:We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently.RESULTS:Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting.CONCLUSIONS:Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies.

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