Researchers from Cleveland Clinic in Ohio, United States sought to compare the expression of microRNAs (miRNAs) in the saliva of patients with hepatocellular carcinoma (HCC) and cirrhosis. They also examined the possibility of using miRNAs as a non-invasive, diagnostic biomarker for HCC. For this, small RNA sequencing was carried out in 20 patients with HCC and 19 patients with cirrhosis; 12 out of the 20 patients with HCC had chronic liver disease. Investigators detected 4565 precursor and mature miRNAs in the saliva of the patients. Of these, 365 were significantly different in patients with HCC versus those with cirrhosis demonstrating a broad shift in profiles of the miRNAs; 283 (78%) of these miRNAs were significantly downregulated in patients with HCC vs cirrhosis; 248 miRNAs were significantly downregulated in patients with both HCC and chronic liver disease versus cirrhosis but no HCC suggesting that the differentially expressed miRNAs were due to the presence of HCC irrespective of the presence of chronic liver disease. A predictive model combining 10 miRNAs and covariates like age, sex, race, smoking and BMI could correctly categorize most cases of HCC signifying that these alterations in miRNA were detected even in early-stage HCC. Expression of three significant miRNAs was different in the tissue of HCC patients compared to cirrhotic liver tissue.

This pilot study has for the first time shown the presence of miRNAs in saliva and also demonstrated their potential as a highly sensitive and specific non-invasive biomarker for HCC. Cirrhosis is well-established as a risk factor for HCC. In such high-risk patients, it serves as a valuable screening tool to identify patients with HCC and may be complementary to the currently available diagnostic methods such as ultrasound and alpha fetoprotein, which lack sensitivity for diagnosis of HCC.

Mariam A, et al. PeerJ. 2022 Jan 5;10:e12715.  doi: 10.7717/peerj.12715.