Introduction
Hepatocellular Carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasm. Owing to the lack of reliable clinical HCC markers, fewer than 20% of patients are diagnosed at a stage where curative treatment can be performed. It is now clear that microRNAs (miRNAs) can potentially regulate every aspect of cellular activity, including differentiation and development and proliferation; they play a role in regulating apoptotic cell death and tumorigenesis. MiRNA‑192 is hepatocyte‑specific miRNA and it is released from damaged hepatocytes early in liver injury in animal models have made miRNA‑192 an attractive biomarker for liver damage. Many studies have demonstrated that miRNA expression profiles in HCC and nontumor tissue are significantly different.
Aims & Methods
The aim is to evaluate the role of serum miRNA‑192 as potential serum marker of HCC among HCV related liver cirrhosis.
The study was carried out on 80 Egyptian patients with HCV related liver cirrhosis (Liver cirrhosis (LC) group: 40 patients with HCV related liver cirrhosis without HCC and HCC group: 40 patients with HCV related liver cirrhosis and HCC) and 20 healthy volunteers as controls from Menoufia University Hospitals (Egypt). They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, albumin, bilirubin, INR}, urea, creatinine, AFP, HBsAg, HCV Ab and serum miRNA‑192). Abdominal ultrasonography was done for all patients and controls. HCC is further confirmed by triphasic CT. Patients with malignancy other than HCC, received previous treatment for HCC or chronic liver disease other than HCV were excluded from the study.
Results
In HCC group, according to BCLC classification, one patient (2.5%) at very early stage, 3 (7.5%) at early stage, 13 (32.5%) at intermediate stage, 8 (20%) at advanced stage and 15 (37.5%) at terminal stage. In HCC group, 10 patients (25%) had HCC size˂3 cm and 30 patients (75%) had HCC size˃3 cm. 65% of the patients (n=26) had single lesion, 5% (n=2) had 2 lesions and 30% (n=12) had multifocal lesions. Eleven patients (27.5%) have portal vein thrombosis (PVT). Serum miRNA‑192 ratio was significantly higher in HCC group (195.8±256.3) than LC (42.6±35.6) and control group (25.7±18.2) (P=0.001 for all) but there was no significant difference between LC and controls (P=0.06). In HCC group, miRNA‑192 ratio was higher in patients with tumor size ˃3 cm (317.9±402) than tumor size ˂3cm (170.7±254.5) (P=0.02) but there was no significant difference according to number of focal lesion or presence of PVT (P˃0.05). AFP level (ng/ml) was significantly higher in HCC group (6572±12563) than LC (28.1±35.1) and control group (14.7±13.3) (P=0.006 for both) but there was no significant difference between LC and controls (P=0.1). Serum miRNA‑192 ratio cutoff level >62.6 have 77.5% sensitivity and 82.5% specificity for detection of HCC. AFP at cutoff level >35.7 ng/ml have 70% sensitivity and 65% specificity for detection of HCC. MELD score, APRI score and FIB-4 were significantly higher in HCC group (20.5±3.5, 3.2±2.7 and 7.2±4.5 respectively) than LC group (7.9±2.2, 0.76±0.92 and 2.3±2.9 respectively) (P˂0.001 for all). In HCC and LC groups, there was a significant positive correlation between miRNA‑192 ratio and AFP (P˂0.001)
Conclusion
MiRNA‑192 could be used as a diagnostic biomarker for detection of HCC in HCV‑related cirrhosis, as it showed significant upregulation in patients with HCC in comparison with non‑HCC patients with higher sensitivity and specificity than AFP for detection of HCC.
References
1-Giordano S and Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology 2013; 57:840–847.
2-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56:1946–1957.
3-Blanco‑Calvo M, Calvo L, Figueroa A, Haz‑Conde M, Anton‑Aparicio L, Valladares‑Ayerbes M. Circulating microRNAs: molecular microsensors in gastrointestinal cancer. Sensors 2012; 12:9349–9362.
4-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases.
Hepatology 2012; 56:1946–1957.
