Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer

Abstract

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are regarded as useful tools for cancer detection, particularly for the early stage; however, little is known about their diagnostic impact on gastric cancer (GC). We hypothesized that GC-related lncRNAs might release into the circulation during tumor initiation and could be utilized to detect and monitor GC. 8 lncRNAs which previously found to be differently expressed in GC were selected as candidate targets for subsequent circulating lncRNA assay. After validating in 20 pairs of tissues and plasma in training set, H19 was selected for further analysis in another 70 patients and 70 controls. Plasma level of H19 was significantly higher in GC patients compared with normal controls (p < 0.0001). By receiver operating characteristic curve (ROC) analysis, the area under the ROC curve (AUC) was 0.838; p < 0.001; sensitivity, 82.9%; specificity, 72.9%). Furthermore, H19 expression enabled the differentiation of early stage GC from controls with AUC of 0.877; sensitivity, 85.5%; specificity, 80.1%. Besides, plasma levels of H19 were significantly lower in postoperative samples than preoperative samples (p = 0.001). In conclusion, plasma H19 could serve as a potential biomarker for diagnosis of GC, in particular for early tumor screening.

Overexpression of long non-coding RNA H19 is associated with unfavorable prognosis in patients with colorectal cancer and increased proliferation and migration in colon cancer cells

“…Furthermore, increased expression of H19 was markedly associated with an early recurrence of bladder cancer and may be considered a predictive marker for poor prognosis (14). Zhou et al (21) revealed that plasma H19 expression enabled the differentiation of early stage gastric cancer from controls with an area under the curve of 0.877, sensitivity of 85.5% and specificity of 80.1% (18).…”

Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines

“…Given that EVs have been detected in many different body fluids, circulating H19 could serve as a biomarker for non-invasive cervical cancer screening, akin to the use of plasma H19 in gastric cancer diagnosis. 41 A growing number of reports have explored the effect of H19 loss-and gain-of-function in various malignancies. 27,[42][43][44] However, data on the role of H19 in cervical cancer remain limited.…”

How can plasma RNA be used to diagnose prostate cancer?

“…Moreover, MALAT-1-derived miniRNA can be used as a novel plasma-based biomarker for PCa detection and can improve diagnostic accuracy by predicting prostate biopsy outcomes. Later, Zhou et al reported the potential diagnostic value of plasma lncRNA H19 in gastric cancer [5]. In addition, in the field of esophageal squamous cell carcinoma diagnosis, plasma lncRNA POU3F3 was able to serve as a potential biomarker [12].…”

“…The quantity of circulating RNAs is also dependent on its degradation and clearance rate. Circulating noncoding RNAs (ncRNAs) have also been thought to be derived from peripheral blood cells [6], although other studies have not found a significant association between plasma long ncRNA (lncRNA) concentrations and peripheral hematocytes [5].…”

“…The increase in plasma/serum RNA may be relevant to apoptosis or necrosis of cancer cells, and fragments of cellular nucleic acid can be actively released into the bloodstream by local or distant tumor cells [4,5]. The proportion of circulating RNAs secreted by tumor cells fluctuates owing to the biological status of the tumor cells.…”