Research Group
Laghi Group
Molecular Gastroenterology Lab
Our lab aims at investigating colorectal and pancreatic cancer using advanced translational approaches, based on large cohorts of patients, with the final goal of better understanding the molecular mechanisms implicated in tumor progression and metastasis and define new prognostic and predictive biomarkers.
The challenge
Colorectal cancer is the third most commonly diagnosed cancer in men, the second most common cancer in women and the second leading cause of cancer death worldwide. Pancreatic cancer, on the other hand, once considered a rare cancer, is a growing cause of concern, with an annual incidence more than doubled from 1990 to 2017, due to population ageing. Age is, in fact, the strongest risk factor for both pancreatic cancer and colorectal cancer, together with smoking tobacco, overweight, diabetes, low-fiber-high-fat diet and alcohol consumption. And both types of cancer are often diagnosed when it is too late: we need new diagnostic and prognostic biomarkers to allow for more personalized and effective treatments.
Main research areas
Genomic instability and mismatch repair defects
Microsatellite Instability acts as stage-dependent predictor of survival in Colorectal Cancer patients alongside a decreased risk of metastases, due to specific genetic and epigenetic changes of the primary tumor. Focusing on the molecular basis of Hereditary Non-Polyposis Colorectal Cancer in the setting of deficient DNA mismatch repair (or Lynch syndrome), a large mono-institutional series of Colorectal Cancer was collected to address the prognostic role of underlying types of genomic instability.
Tumor infiltrating immune cells
Colorectal cancer relies on the TNM classification system to prognosticate the outcome of the disease, yet the information provided by TNM staging is incomplete, and there is a strong need for better biomarkers. Recently, translational studies on the density of tumor infiltrating immune cells pointed to the crucial role of the immune response against colorectal cancer progression. The lab is interested in the characterization of components of the innate and adaptive immune systems as prognostic and predictive biomarkers.
Epithelial-to-Mesenchymal Transition
The heterogeneous microenvironment in the stroma close to the tumor may harbor non-canonical neoplastic cells likely to exploit the Epithelial-to-Mesenchymal Transition (EMT), by which they lose their specificity and cell-to-cell adhesion, becoming multipotent stromal cells able to migrate and invade nearby tissues, eventually contributing to metastasis. After observing specific EMT factors in the blood of patients with colorectal and pancreatic cancer, the lab is assessing the possibility to employ a “liquid-biopsy” test, exploiting such increased levels for an innovative diagnostic approach.
Role of genetic variants on aggressiveness of pancreatic cancer
Despite the recent advances in understanding the genome landscape of pancreatic cancer, the disease remains one of the most lethal, with few therapeutic treatment options. Our data highlight the association between the H63D polymorphism of the HFE gene – a key regulator of iron metabolism – and an increased risk for pancreatic cancer development and aggressiveness. However, the underlying mechanisms are still unclear. Our research aims to clarify the contribution of genetic HFE variants in modifying background host immune response and favoring pancreatic cancer progression.
Selected publications
Combined Low Densities of FoxP3(+) and CD3(+) Tumor-Infiltrating Lymphocytes Identify Stage II Colorectal Cancer at High Risk of Progression.
Results of First-Round of Surveillance in Individuals at High-Risk of Pancreatic Cancer from the AISP (Italian Association for the Study of the Pancreas) Registry.
Protumor Steering of Cancer Inflammation by p50 NF-κB Enhances Colorectal Cancer Progression.
Evolving notions on immune response in colorectal cancer and their implications for biomarker development.
Hereditary or sporadic polyposis syndromes.
Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.
Tumour-associated macrophages as treatment targets in oncology.
Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes.
Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma: Characterization in a 3D-cell culture model.
The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination.
PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer.
Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers.
Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia.
Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours.
Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors.
MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.
Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.
Microsatellite instability and therapeutic consequences in colorectal cancer.
The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker.
CD3+ cells at the invasive margin of deeply invading (pT3-T4) colorectal cancer and risk of post-surgical metastasis: a longitudinal study.
Differences and evolution of the methods for the assessment of microsatellite instability.
Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.
Frameshift mutations of human gastrin receptor gene (hGARE) in gastrointestinal cancers with microsatellite instability.
Lack of mutation at codon 531 of SRC in advanced colorectal cancers from Italian patients.
JC virus DNA is present in the mucosa of the human colon and in colorectal cancers.
Group members
