HomeENGLISH MAGAZINEExtracellular ves(h)icles for tumoral detection: upgrades in biotech for early liver cancer...

Extracellular ves(h)icles for tumoral detection: upgrades in biotech for early liver cancer diagnosis

Primary liver cancer, the third-leading cause of cancer-related death worldwide. New cases and deaths related to liver cancer in Africa, China and the Americas account for about 80% of the total in the world. According to annual forecasts, WHO estimates that at least 1 million patients will die from liver cancer by 2030. Hepatocellular carcinoma (HCC) is highly malignant and usually diagnosed at an advanced stage, accounting for over 80% of liver cancers primarily around the globe. The high mortality rates can be attributed in part to the fact that a significant proportion of patients are found at an advanced stage, when potentially curative treatments are no longer an option. Early diagnosis and a better understanding of the molecular mechanisms leading to its onset and progression are clinically urgent. Unfortunately, today’s screening methods are unable to provide an early and accurate diagnosis on a regular basis.

General guidelines recommend that patients at risk undergo six-monthly liver ultrasound to detect HCC at a curative stage, but ultrasound accuracy remains low, with sensitivity ranging from 60% to 70%, with a specificity of 90%. Clearly, the development of non-invasive tests for early detection is absolutely necessary. Currently, despite enormous efforts have been made to discover new biomarkers for the early diagnosis of HCC, the clinical diagnosis of HCC still depends on imaging and the main protein marker, alpha-fetoprotein (AFP). Metabolic reprogramming is a recognized hallmark of cancer. Metabolites can regulate gene and protein expressions and metabolic proteins and / or metabolites are potential diagnostic and prognostic biomarkers. Reliable results were obtained using some metabolites, such as L-lactic acid, some amino acids, glutamyl-dipeptides, phenylalanyl-tryptofane and glycocolic acid.

Their changes in serum reflect metabolic changes in tumor tissue; and metabolomics certainly represents a giant step in the characterization and early diagnosis of tumors. But it is not the only biomedical path that is being followed. New research led by researchers at UCLA’s Jonsson Comprehensive Cancer Center and involving more than 50 researchers suggests that the new technology under development could lead to a better way to detect early stage hepatocellular carcinoma (HCC), which represents 80% to 85% of primary liver tumors and usually occurs in patients with liver cirrhosis or chronic hepatitis B virus. The experimental technology measures and evaluates nanoparticles, called extracellular vesicles or EVEs, which are released by normal cells but even more so by cancer cells and cells within a tumor microenvironment.

Tumor-associated extracellular vesicles are present in circulation at relatively early stages of the disease and are readily accessible at all stages of the disease. Inside EVEs are proteins, DNA, RNA, metabolites and lipids that reflect the tumor of origin; this makes these particles interesting for the development of cancer biomarkers. In the article, the team of researchers introduced a simplified surface protein assay (HCC EV SPA) capable of dissecting and quantifying eight EVE sub-populations from liver cancer cells. According to the authors, their technology may someday enable rapid, highly sensitive and cost-effective detection of early-stage HCC in patients at risk with liver cirrhosis. It consists of two platform technologies: a) conjugation microspheres for particle purification, and b) a multiplex polymerase chain reaction (Mpx-PCR) to quantify subgroups of EVE from liver cancer cells.

Overall, 99.7% of tissue protein microarray stained positive for at least one of the four common HCC associated protein markers (CD147, GPC3, EpCAM and ASGPR1), which represents a nearly perfect acceptability border. The test has also the ability to distinguish between the cells derived by viral- or nonviral-induced transformation. The authors said the operational kit must be perfectioned and this will happen in short time. IN the meantime, early diagnosis allows doctors and patients to start treatment early, which they expect will have a significant impact on survival rates.

  • Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.

Scientific references

Yang S, Wang J et al. Int J Oncol. 2022 Aug; 61(2):91.

Sun N, Zhang C, Lee YT et al. Hepatology 2022 Jul 31.

Zhu Y, Chen B et al. Front Oncol. 2022 Jul; 12:923890.

Chen YQ et al. Int Immunopharmacol. 2022; 108:108760.

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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