Serum Exosomal Long Noncoding RNAs ENSG00000258332.1 and LINC00635 for the Diagnosis and Prognosis of Hepatocellular Carcinoma

Abstract

Increasing studies suggest that long noncoding RNAs (lncRNAs) are involved in carcinogenesis of human cancers and might be used as diagnostic biomarkers for cancers. A total of 301 participants were recruited in the first part of the study, including a hepatocellular carcinoma (HCC) group ( = 60), liver cirrhosis (LC) group ( = 85), chronic hepatitis B (CHB) group ( = 96), and healthy subjects ( = 60). In the second part, we collected 55 HCC patients, 60 CHB patients, and 60 healthy subjects as an independent cohort to validate the ability of the experiential lncRNAs for identifying HCC from CHB. A commercial kit was used to isolate serum exosomes and total RNA. The relative levels of lnRNAs and mRNA were measured with TaqMan PCR. The results showed that the levels of and in the HCC group were significantly higher than those in the other groups (all < 0.05). A high level in HCC was associated with portal vein tumor emboli, lymph node metastasis, TNM stage, and overall survival (OS; all < 0.05), and a high level was related to lymph node metastasis, TNM stage, and OS (all < 0.05). discriminated HCC from CHB, gaining an area under the ROC curve (AUC) of 0.719 (cutoff value of 1.345); gained an AUC of 0.750 (cutoff value of 1.690). Furthermore, the AUC for the combination of the 2 lncRNAs and serum AFP (cutoff value of 20 μg/L) was 0.894. The abilities of the 2 lncRNAs for identifying HCC from CHB were validated by an independent cohort. The results suggested that the combination of serum exosomal ,, and AFP may be a valuable assay in diagnosis and prognosis of HCC. Our data will shed light on exosomal lncRNAs as biomarkers for HCC. .

<p>Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis</p>

“…22 The analysis of exosomes in plasma or bodily fluids is highly advantageous to pathological biopsy owing to its noninvasiveness and repeatability. Indeed, exosomes are very stable, easy to obtain, and present in almost all body fluids, 23,24 allowing for frequent monitoring of malignancies. In our study, we investigated whether lncRNA serum H19 is present in exosomes and whether exosomal H19 could be utilized as a noninvasive diagnostic tool for breast cancer.…”

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

“…After radical resection of a primary tumor, a significant drop in exosomal miRNA may be observed, indicating that the resected tumor was the primary source of exosomal release. In contrast, stable levels of exosomal miRNA could be indicative of residual disease …”

Circulating tumor DNAs and non-coding RNAs as potential biomarkers for hepatocellular carcinoma diagnosis, prognosis and response to therapy

“…As single biomarkers, results indicated a sensitivity ranging from 51% to 92%. In this experimental setting, lncRNA -uc003wbd [95] , ENSG00000258332.1 [96] , small nucleolar RNA host gene 1 (SNHG1) [97] , zinc finger antisense 1 (ZFAS1) [98] were able to differentiate HCC patients from chronic hepatitis B virus (HBV) patients or healthy controls, urothelial carcinoma associated-1 (UCA1) or WRAP53 [99] were significantly higher in HCC patients' sera in comparison with chronic hepatitis C virus (HCV) patients or healthy volunteers. Diagnostic accuracy improved when lncRNAs were combined among them or with AFP and DCP.…”

“…Some of the studies investigated the combination of lncRNAs. The combined up-regulation of ENSG00000258332.1 and LINC00635 [96] , or of SNHG and UCA1 [106] or low levels of JPX and X inactive-specific transcript (XIST) [101] significantly correlated with a poorer prognosis in HCC patients.…”