Diagnostic and prognostic potential of serum microRNA-4651 for patients with hepatocellular carcinoma related to aflatoxin B1

Abstract

BackgroundThe serum microRNAs have been reported as potential biomarkers for hepatitis virus-related hepatocellular carcinoma (HCC); however, their role in aflatoxin B1 (AFB1)-related HCC to has not yet been evaluated.Materials and MethodsWe conducted a case-control study, including 366 HCC cases and 662 controls without any evidence of tumors, to identify and assess diagnostic and prognostic potential of serum microRNAs for AFB1-related HCC. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to elucidate diagnostic performance, and to compare the microRNAs with α-fetoprotein (AFP) at a cutoff of 20 ng/mL (AFP20) and 400 ng/mL (AFP400).ResultsWe found 8 differentially expressed microRNAs via the microRNA array analysis; however, only microRNA-4651 was further identified to detect AFB1-positive HCC but not AFB1-negative HCC. For AFB1-positive HCC, microRNA-4651 showed higher accuracy and sensitivity than AFP400 (AUC, 0.85 vs. 0.72; Sensitivity, 78.1% vs. 43.0%). Compared to AFP20, microRNA-4651 exhibited higher potential in identifying small-size (0.68 vs. 0.84 for AUC and 36.7% vs. 75.5% for sensitivity, respectively) and early-stage HCC (0.69 vs. 0.84 for AUC and 38.7% vs. 75.7% for sensitivity, respectively). Additionally, miR-4651 was also associated with HCC prognosis (hazard risk value, 2.67 for overall survival and 3.62 for tumor recurrence analysis).ConclusionsThese data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases.

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

“…Microvessel density (MVD) in tumor tissues was evaluated according to our previously published immunohistochemistry . In this study, the MVD was divided into two groups: low density (number of microvessels ≤ 50/×200 magnifications) and high density (number of microvessels > 50/×200 magnifications).…”

“…For survival analysis, all patients with hepatocellular carcinoma were followed up as described in our previous studies . In brief, survival data, including overall survival (OS) and tumor recurrence‐free survival (RFS) status, were confirmed according to patient or family contact and clinic records, and the last follow‐up day was set on July 31, 2017.…”

“…The microRNA‐4651 expression in cancerous tissues was tested using our previously published TaqMan quantitative reverse‐transcription PCR method . Briefly, RNA was first extracted from fresh tumor samples.…”

“…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 . This increasing serum level displays diagnostic and prognostic potential for aflatoxin B1‐related 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. The aims of this study were to explore whether microRNA-4651 in the cancerous tissues modified pa-TACE treatment, thus improving the prognosis of hepatocellular carcinoma.…”