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PLoS One. 2019 Feb 5;14(2):e0211581. doi: 10.1371/journal.pone.0211581. eCollection 2019.

The heterogeneity of plasma miRNA profiles in hepatocellular carcinoma patients and the exploration of diagnostic circulating miRNAs for hepatocellular carcinoma.

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Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Key Laboratory of Oncology in South China/Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, China.


Heterogeneity is prevalent in cancer both between and within individuals. Although a few studies have identified several circulating microRNAs (miRNAs) for cancer diagnosis, the complete plasma miRNA profile for hepatocellular carcinoma (HCC) remains undefined, and whether the plasma miRNA profiles are heterogeneous is unknown. Here, we obtained individualized plasma miRNA profiles of both healthy subjects and HCC patients via genome-wide deep sequencing. Compared with the highly stable miRNA profile of the healthy subjects, the profile of the HCC patients was highly variable. Seven miRNAs were optimized as potential plasma-based biomarkers for HCC diagnosis. Combined with the clinical data of The Cancer Genome Atlas (TCGA) cohort, three out of the seven miRNAs were correlated with the survival of the HCC patients. To investigate the effect of cancer cells on the plasma miRNAs profile, we compared the most differentially expressed miRNAs between plasma and tissues. Furthermore, miRNAseq data of HCC patients from TCGA were recruited for comparisons. We found that the differences between plasma and tissue were inconsistent, suggesting that other cells in addition to cancer cells also contribute to plasma miRNAs. Using two HCC cancer cell lines, we examined the levels of seven differentially expressed miRNAs. The reverse direction of certain miRNAs alterations between cancer cells and media further confirmed that miRNAs may be selectively pump out by cancer cells.

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Conflict of interest statement

The authors have declared that no competing interests exist.

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