Open AccessEarly detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle‐derived long noncoding RNAs identified as markers
Author(s) -
Kim Soon Sun,
Baek Geum Ok,
Son Ju A,
Ahn Hye Ri,
Yoon Moon Kyung,
Cho Hyo Jung,
Yoon Jung Hwan,
Nam Suk Woo,
Cheong Jae Youn,
Eun Jung Woo
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13049
Subject(s) - hepatocellular carcinoma , malat1 , long non coding rna , biology , cancer research , oncogene , extracellular vesicle , extracellular vesicles , rna , microrna , gene , microvesicles , microbiology and biotechnology , genetics , cell cycle
This study investigated the diagnostic potential of serum small extracellular vesicle‐derived long noncoding RNAs (EV‐lncRNAs) for hepatocellular carcinoma (HCC). Driver oncogenic lncRNA candidates were selected by a comparative analysis of lncRNA expression profiles from two whole transcriptome human HCC datasets (Catholic_LIHC and TCGA_LIHC). Expression of selected lncRNAs in serum and small EVs was evaluated using quantitative reverse transcription PCR. Diagnostic power of serum EV‐lncRNAs for HCC was determined in the test ( n = 44) and validation ( n = 139) cohorts. Of the six promising driver onco‐lncRNAs, DLEU2 , HOTTIP , MALAT1, and SNHG1 exhibited favorable performance in the test cohort. In the validation cohort, serum EV‐ MALAT1 displayed excellent discriminant ability, while EV‐ DLEU2 , EV ‐HOTTIP, and EV‐ SNHG1 showed good discriminant ability between HCC and non‐HCC. Furthermore, a panel combining EV‐ MALAT1 and EV‐ SNHG1 achieved the best area under the curve (AUC; 0.899, 95% CI = 0.816–0.982) for very early HCC, whereas a panel with EV‐ DLEU2 and alpha‐fetoprotein exhibited the best positivity (96%) in very early HCC. Serum small EV‐ MALAT1 , EV‐ DLEU2 , EV‐ HOTTIP, and EV‐ SNHG1 may represent promising diagnostic markers for very early‐stage HCC.