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Biology subjects

D'Angelo, R.

Publications and source records attributed to D'Angelo, R..

2 recordsLinked to original sources

Differential serum binding patterns predicting healthy subjects and cancer patients

A viral exposure signature (VES) has been previously described predicting the development of Hepatocellular carcinoma (HCC) in at-risk patients. This has been achieved by a serological profiling of the viral infection history using a synthetic human virome including >100k epitopes (VirScan). In the present study we applied the same VirScan strategy to identify a differential serum binding pattern (DSBP) for classifying patients of different cancer types from healthy individuals. In particular, the healthy group included both age-matched (ADULTS) as well as elderly (ELDERS) individuals, the latter counting also nonagenarians and centenarians. The class comparison performed with serological data show DSBPs supporting class predictions, as confirmed by the receiver operating characteristic (ROC) curve analysis. Antibody responses supporting the class predictions are specific to peptides from persistent herpesviruses, acute-infecting viruses and, consistently in all comparisons, human respiratory syncytial virus (HRSV). Strikingly, the DSB of the ELDERS vs. CANCER comparison is characterized by higher titers in the healthy subjects; on the contrary, the DSB of the ADULTS vs. CANCER comparison is characterized by lower titers in the healthy subjects. Overall, the results show a differential serological binding pattern predicting healthy individuals (ADULTS or ELDERS) from patients with different types of cancer. Such results provide the first evidence suggesting a close link between anti-microbial immunity and cancer development. They may be of the highest relevance in terms of predictive, diagnostic and/or prognostic impact in oncology.

immunology↗

Mutants of p53 sustain tumor growth under mechanical compression

ContextSolid tumors are subjected to mechanical stimuli arising from their growth in confined environments. Growth-induced pressure builds up in tumors such as pancreatic cancer and rises alongside the occurrence of genetic alterations during tumorigenesis. This study aims to understand the so far unknown relationship between genetic alterations and cancer cell behavior under compressive stress. ResultsUsing isogenic cell lines with engineered p53 mutations, we showed that the p53 background influences cell response to compression. Tumor growth under compression increased in cells harboring a mutated-truncated p53 form. This mutation blocked caspase 3 cleavage and promoted survival and growth through PI3K-AKT activation and dysregulation of c-FOS and FOSB transcription factors network. Mutated-truncated p53 cells displayed a unique behavior and heightened an activation state under compression. ConclusionMechanical compression and p53 mutations together drive tumor growth. p53 status could be a biomarker for predicting tumor adaptation to mechanical stress and efficiency of therapies targeting mechanosensitive pathways. TeaserMechanical compression and p53 mutations together enhance cancer cell survival and growth, driving solid tumor progression.

cancer biology↗