The survival of oral carcinoma, on average 50% at 5 years, is strongly influenced by the stage in which the disease comes
diagnosed.
Tissue biopsy is the gold standard for obtaining a certain diagnosis; the latter, however, may present some
problems that may actually limit its use, such as patient comorbidities or the risk of causing micro-metastases by oncological cell dissemination.
For this reason, a new diagnostic and follow-up method was introduced in the field of oncology: the liquid biopsy.
Liquid biopsy is a simple, rapid and minimally invasive method which consists of a blood and / or saliva collection in order to
to analyze some biomarkers that can affect oncogenic or tumor suppressor mechanisms.
The main purpose of the research is to analyze the expression profile of some microRNAs (miRNAs) in order to evaluate them
use as diagnostic and / or prognostic biomarkers in patients with squamous cell carcinoma of the oral cavity (SCOC).
In particular the following miRNAs will be analyzed: miRNA-29b, miRNA-31, miRNA-21, miRNA- 1246, miRNA-184, miRNA-
424, miRNA-135b, miRNA-766, miRNA-145 and miRNA-378.
Adult Caucasian patients, affected by OSCC or by potentially malignant epithelial lesions (PMEL) belonging to the DAI Head-Neck of Sapienza University of Rome, will be enrolled in the study. The tissue samples and liquids taken will be sent to the molecular epidemiology laboratory, Sapienza University of Rome, where they will be processed for the extraction of the aforementioned miRNAs. The advantages of liquid biopsy are to be considered not only in the early diagnosis and evaluation of various tumor genetic determinants, but also in the evaluation of the response to chemo or radiotherapy treatment, as well as in the monitoring of residual disease.
Squamous cell carcinoma of the oral cavity (SCCOC) is one of the 10 most common cancers worldwide, with an estimated incidence in Italy of about 16 new cases per 100,000 inhabitants a year. The onset of SCCOC depends on multistep carcinogenic pathways that
include cumulative genetic alterations and epigenetic alterations that lead to a loss of cell cycle control (1,2). The neoplastic cells are in continuous and constant communication with the surrounding microenvironment and their survival depends on it. This dialogue takes place through complex mechanisms, only partially known, in which microRNAs intervene.
MicroRNAs are a group of small RNAs, 19-25 nucleotides in length, involved in the regulation of development and cell differentiation, proliferation and survival. They perform their actions with two mechanisms: degradation of messenger RNA and inhibition of translation. A single mRNA is usually translated into a single protein; however, a single miRNA is able to regulate the translation of a multitude of genes targeting specific regions in the 3'-UTR of their mRNA transcripts. Changes in mRNA levels can ultimately be controlled or reversed by post-transcriptional regulation; thus, miRNA expression levels may provide a better indication of a cell's physiological status than mRNA expression (4).
Recent studies have shown that miRNAs can be isolated from fresh tissues and body fluids, and the level of expression of
some of them reflect the physiopathological state of a tissue and have been shown to be specific for particular pathological states (5).
Furthermore, miRNAs are more stable than mRNAs and therefore less prone to minor differences in sample processing. Together, these features make them excellent biomarker candidates. Easily accessible body fluids such as blood derivatives and saliva would provide an ideal source for miRNA biomarkers.
To date, the OSCC is burdened with high mortality with survivals on average of 50% 5 years after diagnosis. The poor survival depends mainly on diagnostic as well as therapeutic delays.
The liquid biopsy, already used for other neoplasms, such as squamous cell carcinoma of the esophagus, non-small cell lung cancer, pancreatic adenocarcinoma and breast cancer (6) etc., could also play a role in SCCOC great importance for the early diagnosis of disease, for monitoring the response to therapy, and as an early indicator of relapses. Compared to the traditional tissue "solid biopsy", which cannot always be performed to determine tumor dynamics, liquid biopsy has considerable advantages as it is a non-invasive mode that can provide diagnostic and prognostic information before treatment, during treatment and can be used to identify any progression early.
The introduction of this method in daily practice for the diagnosis, but above all for the follow-up, would revolutionize the approach to the disease allowing the patient to be monitored more frequently in a longitudinal way after primary therapy in order to promptly detect and deal with any recurrences of illness or problems related to it and to carry out treatment as personalized as possible.
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2.Al-Kaabi A, van Bockel LW, Pothen AJ, Willems SM (2014) p16INK4A and p14ARF gene promoter hypermethylation as prognostic
biomarker in oral and oropharyngeal squamous cell carcino- ma: a review. Dis Markers 2014: 2605496.
3. Laco J, Nekvindova J, Novakova V, Celakovsky P, Dolezalova H, Tucek L et al (2012) Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16 (INK4a) expression, and HPV status. Neoplasm 59: 398-408.
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5.Alevizos I, Illei GG (2010) MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol 6: 391-8.
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