We have shown genetic alterations and microRNA dysregulation in hematopoietic and solid tumors, including lung cancer, the major cause of cancer death in the USA. Recently, we explored microRNA expression profiles in lung tumors, normal lung tissues and plasma samples from cases with variable prognosis involved in a completed spiral CT screening trial with extensive follow up. The trial involved 1025 individuals age 50 years or older, who smoked at least a pack of cigarettes a day for 20 years or more. Profiling of plasma samples collected 1-2 years before the onset of disease, at the time of CT detection, and in disease-free smokers enrolled in the screening trial, provided microRNA expression signatures with strong predictive, diagnostic and prognostic potential (Boeri M. et al. microRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer, Proc. Nat. Acad. Sci. USA, 108:3712-3718, March 1, 2011). These signatures were validated in an independent cohort from a second randomized spiral - CT trial. These results indicate a role of microRNAs as molecular predictors of lung cancer development and aggressiveness and have important clinical implications for lung cancer management. We propose to validate these signatures by using NanoString technology and deep sequencing of microRNAs by taking advantage of large cohorts of patients at NYU (Dr. H. Pass) and at the National Cancer Institute of Italy, Milan, (Drs. U. Pastorino and G. Sozzi). In addition, we propose to investigate the dysregulation of larger non-coding RNAs in the tumors, normal tissues and plasma in the same cohorts of patients, since it could provide novel powerful biomarkers for the early detection and prevention of lung cancer.
Lung cancer is the first cause of cancer death in the USA and is, for the most part, incurable. We propose to develop reliable and powerful biomarkers capable to detect malignant disease long before lung cancer is clinically detectable by using a non-invasive approach exploiting microRNA and lncRNA dysregulation in plasma of individuals at risk.
| Pastorino, Ugo; Morelli, Daniele; Marchianò, Alfonso et al. (2018) Inflammatory status and lung function predict mortality in lung cancer screening participants. Eur J Cancer Prev 27:289-295 |
| Kim, Taewan; Croce, Carlo M (2018) Long noncoding RNAs: Undeciphered cellular codes encrypting keys of colorectal cancer pathogenesis. Cancer Lett 417:89-95 |
| Acunzo, Mario; Romano, Giulia; Nigita, Giovanni et al. (2017) Selective targeting of point-mutated KRAS through artificial microRNAs. Proc Natl Acad Sci U S A 114:E4203-E4212 |
| Infante, Maurizio; Sestini, Stefano; Galeone, Carlotta et al. (2017) Lung cancer screening with low-dose spiral computed tomography: evidence from a pooled analysis of two Italian randomized trials. Eur J Cancer Prev 26:324-329 |
| Borzi, Cristina; Calzolari, Linda; Centonze, Giovanni et al. (2017) mir-660-p53-mir-486 Network: A New Key Regulatory Pathway in Lung Tumorigenesis. Int J Mol Sci 18: |
| Verri, Carla; Borzi, Cristina; Holscher, Todd et al. (2017) Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening-Detected Lung Cancers. J Thorac Oncol 12:922-931 |
| Pekarsky, Yuri; Balatti, Veronica; Palamarchuk, Alexey et al. (2016) Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc Natl Acad Sci U S A 113:5071-6 |
| Karras, Jenna R; Schrock, Morgan S; Batar, Bahadir et al. (2016) Fhit loss-associated initiation and progression of neoplasia in vitro. Cancer Sci 107:1590-1598 |
| Nigita, Giovanni; Acunzo, Mario; Romano, Giulia et al. (2016) microRNA editing in seed region aligns with cellular changes in hypoxic conditions. Nucleic Acids Res 44:6298-308 |
| Peng, Yong; Croce, Carlo M (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1:15004 |
Showing the most recent 10 out of 48 publications
