Colorectal cancer (CRC) is the second most common tumor type for women and the third for men. CRC develops according to a progressive sequence where some cells from the normal colonic epithelium can transform into polyps, progress into benign adenomas and finally become an invasive cancer.
If diagnosed at early stages, when the tumor is still localized into the colon, CRC has a high survival rate. At this step of its progression removal of polyps or adenomas can even avoid the development of cancer.
CRC screenings on healthy individuals between 50-69 years, through tests for the detection of occult blood in stool (FIT) followed by colonoscopy in case of positivity, has increased the early detection of the disease and reduced of 20-30% CRC deaths. However the test currently used for the screening has sub-optimal sensitivity and specificity, especially for precancerous lesions.
Our aim is to identify biomarkers for the non-invasive detection of early stage CRCs or of precancerous lesions (polyps or adenomas). Expression profiles of microRNAs (miRNA, small RNAs that are not translated into a protein but can regulate the expression of genes or proteins) in plasma from individuals carrying CRC or precancerous lesions will be investigated, to identify possible miRNAs associated with presence of cancerous or precancerous lesions.
We are also developing 3D-organoids from CRC and normal tissue, a more relevant model than 2D cultures and easier to manipulate than mouse models, to use for identify new molecular targets for CRC and develop new therapeutic approaches.
The group includes researchers and clinicians belonging to the fields of biology, biostatistics, endoscopy and surgery. The different expertise allows to conduct studies involving a huge number of subjects whose biological samples are collected and processes under controlled conditions. In addition it makes available pathobiological/molecular information as well as the clinical history of each individual that can be easily integrated.
Role in the project, experimental design
Our group is analyzing miRNA expression profiles of plasma from subjects enrolled in the CRC screening program and that resulted positive to the occult blood stool test (FIT) and had colonoscopy at one of the 10 Hospitals in Milan that participate to the screening, including our Institute. The predictive ability of miRNAs in detecting presence of lesions is evaluated through the comparison between their expression levels in individuals resulting, after colonoscopy, with precancerous or cancerous lesions versus those without lesions.
Using samples collected at our Institute, we have identified a group of candidate miRNAs that, appropriately combined in “molecular signatures”, show promising performance in predicting the presence of both precancerous and cancerous endoscopic lesions.
(Colorectal Cancer Clinical Validation Study)
Our objective is now to assess the performance of these signatures on an independent cohort of cases consisting in about 1200 samples collected in the 9 Hospitals involved in the CRC screening program. After that, we will develop an optimized and easy-to-use kit for their estimation and we will test the performance of signatures on prospectively collected samples from FIT+ subjects. Finally, we will evaluate its suitability in a routine clinical setting within the actual CRC screening program (i.e. clinical utility) in order to assess the potential gain derived by the introduction of the miRNA-based test within the CRC screening program.
Our approach will allow the development of a minimally invasive assay for the detection of plasma circulating biomolecular markers that could be used to improve early diagnosis of CRC.
PhD, Staff Scientist
PhD, Staff Scientist
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