Salivary Biomarkers For Liver Cancer Diagnosis

A group of ribonucleic acids..Sensitive salivary biomarkers in diagnosis of cancers!

The postulation that RNA and DNA govern each and every function of the human body is now becoming apparent owing to the continuously evolving and expanding field of genomics, proteomics molecular biology, bioinformatics and so on.. There is a substantial enhancement in understanding several crucial pathways and mechanisms within the human body. Some of these include deciphering the human genome to identification of different types of nucleic acids, their regulation and functions in normal human growth and development and consequences of their abnormal function.

The central dogma of molecular biology as depicted in figure 1 describes mainly the two processes: transcription of genetic information from DNA to RNA and translation of this information for of RNA to produce proteins.

However, the point to be noted here is that approximately only 1% of the entire genome of an individual is protein coding with understanding the function of the remaining region in process. Also, except for the mRNA, tRNA, rRNA (ribosomal RNA) which are involved in translation, there are several other species of RNA within the body which does not produce proteins but are involved in several other vital functions. Few of these include microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs as depicted in figure 2. Herewith the discussion will be focused on long no-coding RNAs (lncRNAs) and its role in cancers, particularly, hepatocellular carcinoma (HCC).

Liver cancer contributes significantly to mortality and morbidity rates globally. Of this group, almost 90% of cases are of hepatocellular carcinomas. Curative hepatectomy can improve the 5-year survival rate to 69%, but unfortunately, approximately 80% of patients with HCC are untreatable because of advanced tumor stages at presentation. And this necessitates the early diagnosis of HCC. Several studies have identified lncRNAs in the tissues and blood of the individuals having hepatocellular carcinomas (HCC). Cancerous tissues continuously undergo necrosis and apoptosis followed by abnormal division of cells. These tissues then secrete lncRNAs into the blood by necrosis and apoptosis.

Saliva has many advantages as a diagnostic sample because of its non-invasiveness, easy collection, and low cost. Also, those taking samples require no professional training or examinations. Saliva sampling is extremely safe and does not induce blood-borne diseases, anxiety, or discomfort. Saliva collection increases the willingness of people to undergo health examinations and will greatly enhance the opportunity to monitor their health more particularly in devastating conditions like cancers. The term “salivaomics” highlights the term “omics” constituted by molecules in saliva that can be used for biomarker development and personalized medicine. Numerous molecules isolated from saliva have been proposed as disease biomarkers for diagnosis, prognosis, drug monitoring and pharmacogenetic studies. Saliva is considered as the end product of blood circulation owing to the extensive blood supply to the salivary glands. Also, it includes several components of blood, since the salivary acinar cells produce saliva using blood materials. And this is the reason why saliva can play diagnostic roles in various diseases.

Different pathways associated with lncRNAs involved in human physiology and pathology are depicted in figure 3.

Studies reported that the lncRNAs, more particularly the lnc-PCDH9-13:1 were found to be overexpressed in HCC tissue and plasma and saliva of HCC patients, and its levels in tissue correlated significantly with those in plasma and saliva. Studies also suggested that the aberrant expression of salivary these lnc-PCDH9-13:1 might aid in determining the diagnosis and prognosis of HCC. Bioinformatic analysis showed that lnc-PCDH9-13:1 played significant roles with dozens of cancer genes in HCC development. The biomarkers, Alpha-fetoprotein-L3 (AFP-L3) and Des-γ- decarboxyprothrombin (DCP) were reported to be promising biomarkers for HCC, however, their diagnostic accuracy remains controversial, since their levels are elevated even in benign liver diseases such as chronic or viral hepatitis, cirrhosis etc. LncRNA is emerging as a new regulator of diverse physiological functions. Specifically, the differential expression of lncRNAs along with other molecular defects, play a significant role in understanding oncogenesis and tumor development.

 

 Abbreviations:

mRNA: messenger RNA

tRNA: transfer RNA

rRNA: ribosomal RNA

siRNAs: short-interfering RNAs

piRNAs: piwi-interatcting RNAs

snRNAs: small nuclear RNAs

snoRNA: small nucleolar RNAs

exRNAs: extra-cellular RNAs

scaRNAs: small Cajal body-specific RNAs

Author: Dr. Shruti Pande

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