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Low-level expression of microRNA-375 predicts poor prognosis in hepatocellular carcinoma

  • Original Article
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Tumor Biology

Abstract

MicroRNAs are predicted to play fundamental roles in the tumorigenesis of hepatocellular carcinoma (HCC). MiR-375 is frequently downregulated in HCC and acts as a tumor suppressor by targeting multiple oncogenes. The objective of this study was to evaluate miR-375 expression and its relevance to the prognosis of HCC. MiR-375 expression was measured in cancerous tissues using qRT-PCR and dichotomized based on a median cutoff. The association between miR-375 expression and clinicopathological parameters and prognosis was subsequently determined. Expression levels of miR-375 were detected in a cohort of 38 HCC patients who underwent curative surgery. No significant correlations were observed between miR-375 expression and clinicopathological parameters, such as gender, age, performance status, preoperative serum AFP level, histological grade, HBV-DNA copy number, ascites, cirrhosis, tumor size, number of tumor nodules, and macrovascular invasion. However, miR-375 expression differs across CLIP scores significantly (p < 0.05). A trend toward poorer disease-free survival (DFS) was observed in patients with lower miR-375 expression compared to those with higher miR-375 expression (p = 0.307). Multivariate analysis demonstrated that low miR-375 expression was an independent prognostic predictor for progression (p = 0.032, risk ratio 3.273). Subgroup analysis revealed that low expression of miR-375 was significantly associated with adverse DFS in patients with poorly differentiated histology, higher serum AFP level (≥400 ng/ml), and advanced tumor stage (CLIP score 1∼3) (p = 0.017, 0.009, and 0.024, respectively). Our study demonstrates that miR-375 expression is significantly correlated with DFS and may be a potential prognostic biomarker of disease progression in HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

AFP:

Alpha-fetoprotein

ECOG PS:

The Eastern Cooperative Oncology Group Performance Status

CLIP:

The Cancer of the Liver Italian Program

TACE:

Transcatheter hepatic arterial chemoembolization

DFS:

Disease-free survival

OS:

Overall survival

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81101588).

Conflicts of interest

None.

Authors’ contributions

Na Zhou: conceived the study and managed its design and coordination.

Jinhua Wu and Wang Xiang: analysis and interpretation of data.

Zhao Sun and Qin Han: have given final approval of the version to be published.

Lin Zhao: have made substantial contributions to conception and design.

Author information

Authors and Affiliations

  1. Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

    Na Zhou, Xiang Wang, Zhao Sun & Lin Zhao

  2. Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China

    Jinhua Wu & Qin Han

Authors
  1. Na Zhou
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  2. Jinhua Wu
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  3. Xiang Wang
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  4. Zhao Sun
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Corresponding author

Correspondence to Na Zhou.

Additional information

Highlights

1. Low miR-375 expression is an independent prognostic predictor for HCC patients.

2. Low-level expression of miR-375 is significantly associated with DFS in patients with poorly differentiated histology, a higher serum AFP level (≧400 ng/ml), and advanced tumor stage (CLIP score 1∼3).

3. No significant correlations were observed between miR-375 expression and clinicopathological parameters.

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Supplementary Fig. 1

The melting curves and amplification curves of real-time PCR of miR-375. (A) melting curves; (B) amplification curve (JPEG 26 kb)

High Resolution Image (TIFF 1947 kb)

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Zhou, N., Wu, J., Wang, X. et al. Low-level expression of microRNA-375 predicts poor prognosis in hepatocellular carcinoma. Tumor Biol. 37, 2145–2152 (2016). https://doi.org/10.1007/s13277-015-3841-0

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  • DOI: https://doi.org/10.1007/s13277-015-3841-0

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