Clinical Research Papers:

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

Xue-Min Wu _, Zhi-Feng Xi, Pinhu Liao, Hong-Dong Huang, Xiao-Ying Huang, Chao Wang, Yun Ma, Qiang Xia, Jin-Guang Yao and Xi-Dai Long

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Oncotarget. 2017; 8:81235-81249. https://doi.org/10.18632/oncotarget.16027

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Xue-Min Wu1,*, Zhi-Feng Xi2,*, Pinhu Liao3,*, Hong-Dong Huang4,*, Xiao-Ying Huang1,*, Chao Wang3,*, Yun Ma5, Qiang Xia2, Jin-Guang Yao1 and Xi-Dai Long1,2

1 Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China

2 Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

3 Department of Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China

4 Division of Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

5 Department of Pathology, The Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China

* These authors have contributed equally to the manuscript

Correspondence to:

Xi-Dai Long, email:

Keywords: microRNA-4651, aflatoxin B1, hepatocellular carcinoma, diagnostic and prognostic biomarkers

Received: November 22, 2016 Accepted: February 18, 2017 Published: March 08, 2017


Background: The 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 Methods: We 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).

Results: We 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).

Conclusions: These data suggest that serum microRNA-4651 may be a useful marker for HCC diagnosis and prognosis, especially AFB1-positive cases.

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