Identification of recurrence-related serum microRNAs in hepatocellular carcinoma following hepatectomy

Abstract

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Prognosis of patients with HCC is generally poor due to the high recurrence rate. In the present study, TaqMan Real-time PCR microRNA Array was used to identify differentially expressed miRNAs from 10 tumor tissue samples (5 from recurrence group vs. 5 from non-recurrence group) and the matched serum samples. Four differentially expressed miRNAs (miR-486–5p, miR-422a, miR-125b and miR-139–5p) were further quantified in 20 tumor tissues and 116 HCC patients' serum before they received hepatectomy. Univariate analysis revealed that miR-486–5p, miR-422a and miR-125b were significantly associated with patients' relapse free survival (RFS). Multivariate analysis demonstrated that miR-486–5p, AFP and microvascular invasion (MVI) were the independent prognostic factors associated with RFS in this cohort (p = 0.000, 0.043, 0.000, respectively). Besides, the expression levels of miR-486–5p were positively correlated in tumor tissues and the paired serum samples, so was miR-422a. The probability of the prognostic accuracy of miR-486–5p in predicting postoperative recurrence of HCC within the first year was 76.79% (65.38% specificity and 81.58% sensitivity), which was almost equal to the classifier established by combination of AFP and MVI (75.98% probability, 63.13% specificity and 85.90% sensitivity). Furthermore, the combination of AFP, MVI and miR-486–5p yielded a ROC curve area of 88.02% (69.20% specificity and 92.10% sensitivity). Our study was the first to identify that serum miR-486–5p could be used to stratify the patients with higher recurrence risk before hepatic resection and potentially guide more effective surveillance strategies for them.

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection

“…Especially serum miR-486-5p, in combination with alpha-fetoprotein levels and microvascular invasion, was found to predict risk of recurrence [33]. Following this approach, a highly sensitive digital droplet PCR of serum samples from our patients with elevated intratumoral miR-135a expression remained negative in our hands (data not shown).…”

MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

“…Its downregulation in tumoral versus normal tissue has been reported in osteosarcoma [21], in colorectal cancer [13, 22], hepatocarcinoma [14] and gastric tumors [23]. A low expression of miR-422a is a marker of poor prognosis in osteosarcoma [21] and colorectal cancer [24] and of poor RFS in hepatocarcinoma [25]. It has also been associated with chemo-resistance in osteosarcoma [26].…”

“…It has also been associated with chemo-resistance in osteosarcoma [26]. Its level of expression in tumors and in serum have been significantly correlated [25], paving the way for its establishment as a companion test. Salivary miRNA profiling has been developed for oral cancer [27].…”

Development of a radiofrequency ablation platform in a clinically relevant murine model of hepatocellular cancer

“…The accumulated results from 3 animals at each timepoint were shown in Figure 2B. The results suggest that RFA performed at 85 C for 60 s results in uniform and predictable liver damage in an area of approximately 50 mm 2 and at a depth of about 3 mm.…”

“…1,2 Annually it results in approximately 700,000 deaths worldwide. 3,4 Current treatments for HCC have demonstrated limited benefit as survival is poor even for patients with localized disease.…”