Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma

Abstract

Our recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC.

Micro RNA‐4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy

“…In the present study, the pa‐TACE procedure was accomplished as the postoperative adjuvant part of the initial therapy procedure for eligible patients with hepatocellular carcinoma (Table ), which started 4 weeks after the removal of tumors. This postoperative adjuvant therapy contains an injection consisting of a mixture of doxorubicin (65 mg/m 2 ), cisplatin (7 mg/m 2 ), and lipiodol, as previously described . Adverse reactions related to pa‐TACE were graded according to the World Health Organization criteria.…”

“…All clinicopathological data, including gender, age, ethnicity, HBV and HCV infective status, liver cirrhosis, tumor grade and stage, and treatment information, were obtained as described previously. (22) Surgically removed fresh samples with hepatocellular carcinoma of all patients were collected for testing microRNA-4651 expression. In this study, HBV and HCV infective status was defined according to the hepatitis B surface antigen (HBsAg) and anti-HCV, respectively.…”

“…This postoperative adjuvant therapy contains an injection consisting of a mixture of doxorubicin (65 mg/m 2 ), cisplatin (7 mg/m 2 ), and lipiodol, as previously described. (22) Adverse reactions related to pa-TACE were graded according to the World Health Organization criteria.…”

“…Some of them, such as microRNA-629, microRNA-1268a, and microRNA-24, have been reported to have early diagnostic and prognostic potential for hepatocellular carcinoma. (22)(23)(24)(25)(26) Our previous studies have shown that a higher serum level of microRNA-4651, a short-strand RNA encoded by the microRNA-4651 gene (located at the 75915197th to 75915269th base of chr7), is found in patients with aflatoxin B1-positive hepatocellular carcinoma. (27,28) This increasing serum level displays diagnostic and prognostic potential for aflatoxin B1-related hepatocellular carcinoma.…”

“…To date, more than 1,800 microRNAs have been identified in the mammalian genome (miRDatabase). Some of them, such as microRNA‐629, microRNA‐1268a, and microRNA‐24, have been reported to have early diagnostic and prognostic potential for hepatocellular carcinoma . Our previous studies have shown that a higher serum level of microRNA‐4651, a short‐strand RNA encoded by the microRNA‐4651 gene (located at the 75915197th to 75915269th base of chr7), is found in patients with aflatoxin B1‐positive hepatocellular carcinoma .…”