Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection

English version

Autoři: Sung Kyu Song ^aff001; Woon Yong Jung ^aff002; Seung-Keun Park ^aff003; Chul-Woon Chung ^aff001; Yongkeun Park ^aff001
Působiště autorů: Department of Surgery, Catholic Kwandong University International St. Mary’s Hospital, Incheon, Republic of Korea ^aff001; Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, Republic of Korea ^aff002; Department of Supercomputing M&S Technology Development, Korea Institute of Science and Technology Information, Daejeon, Republic of Korea ^aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0216847

Souhrn

Background

Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance.

Materials and methods

Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated.

Results

Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, three miRNAs were validated using TCGA database. miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no gross VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and low expression of miR-100-5p were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, low expression of miR-100-5p and miR-148a-3p were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including “invasion and metastasis.”

Conclusions

Low expressions of miR-100-5p and miR-148a-3p were associated with gross VI and poor survival of patients after hepatic resection for HCC.

Klíčová slova:

Biology and life sciences – Genetics – Gene expression – Genomics – Genome analysis – Biochemistry – Nucleic acids – Computational biology – Physical sciences – Research and analysis methods – Database and informatics methods – Gene regulation – Mathematics – Medicine and health sciences – RNA – Non-coding RNA – Statistics – Mathematical and statistical techniques – Statistical methods – Research design – Gastroenterology and hepatology – Liver diseases – Oncology – Cancers and neoplasms – Clinical research design – Natural antisense transcripts – MicroRNAs – Surgical and invasive medical procedures – Digestive system procedures – Gastrointestinal tumors – Biological databases – Metastasis – Basic cancer research – Carcinomas – Genomic databases – Genomic medicine – Cancer genomics – Hepatocellular carcinoma – Hepatic resection – Surgical resection – Survival analysis

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