Prognostic effect of IL-6/JAK2/STAT3 signal-induced microRNA-21-5p expression on short term recurrence of hepatocellular carcinoma after hepatectomy.

Aim: To investigate the putative role of interleukin (IL)-6/Janus Kinase (JAK) 2/Signal transducers and activators of transcription (STAT) 3 signaling pathway in hepatocellular carcinoma (HCC) short term recurrence (STR), and whether the pathway promotes HCC progression through microRNA-21-5p (miRNA-21).

Methods: Immunohistochemistry was performed to evaluate the protein expression of IL-6, JAK2 and STAT3. Real-time PCR was used to evaluate the miRNA-21 expression. We also analyzed the correlation of IL-6, JAK2 and STAT3 protein expression with miRNA-21. Clinicopathological variables, including prognosis, were compared between low and high-expressing groups of miRNA-21.

Results: miRNA-21 expression was significantly increased in the HCC tumor tissue compared to the non-tumor tissue. IL-6 and STAT3 high expression was significantly correlated to high miRNA-21 expression in HCC tumor tissues. Patients with high miRNA-21 expression have more frequent early recurrence. The 6 month overall survival and disease-free survival rate of the miRNA-21 high groups were 72.1% and 30.8%, respectively. Moreover, high miRNA-21 expression was correlated with disease-free survival (DFS) (P < 0.05) and overall survival (OS) (P < 0.05). Multivariate analysis revealed that miRNA-21 and STAT3 high expression were independent prognostic factors of DFS and OS. The area under the ROC curve (AUC) of miRNA-21 and STR, DFS, OS was 0.951 (P < 0.001), 0.847 (P < 0.001), 0.844 (P < 0.001), respectively.

Conclusions: miRNA-21 expression, induced by IL-6/JAK2/STAT3 signaling pathway, was increased in the early recurrence of HCC patients and indicated poor prognosis. Expression analysis of miRNA-21 revealed that it may be a valuable prognostic biomarker for HCC.