Circulating CUDR, LSINCT‐5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls

Abstract

The examination of circulating nucleic acids (CNAs) is an emerging noninvasive diagnostic technique. However, it is unclear if serum long noncoding RNAs (lncRNAs) represent a novel marker to detect gastric cancer (GC). In this study, we measured 39 candidate cancer-associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) in sera from 110 patients with GC, 106 age-and sex-matched healthy subjects and 15 patients with gastric peptic ulcer, markers were validated and assessed by RT-qPCR. The correlation of the expression levels of the candidate serum lncRNAs with clinical parameters of GC patients was performed. A three-lncRNA signature, including CUDR, LSINCT-5 and PTENP1, was identified that may be potential diagnostic marker for GC. The areas under the receiver operating characteristic (ROC) curve for this serum three-lncRNA signature were 0.920 and 0.829 for the two sets of serum samples. Moreover, a risk model for the serum three-lncRNA signature demonstrated that healthy samples can be distinguished from early GC samples. Three-lncRNA signature in serum was identified as diagnostic marker for GC. This work may facilitate the detection of GC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis.Gastric cancer (GC) is the fourth most common type of cancer and the second leading cause of cancer-related deaths worldwide. 1 Surgical resection is the most effective treatment and prolongs the survival of patients with early GC; however, the prognosis for patients with advanced GC is poor, despite recent improvements in chemotherapy and radiotherapy. 2 Improvements in diagnosis are urgently needed to increase the long-term survival of patients with resectable-stage GC.Ideally, biomarkers should be easily accessible and sampled noninvasively. Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free sera, plasma and other bodily fluids of healthy subjects and cancer patients. We have previously demonstrated that human serum or plasma contains microRNAs (miRNAs) that are significantly up-regulated or down-regulated in various types of cancer and are of good diagnostic value for screening. 3-5 However, the identification of miRNAs as biomarkers has yielded inconsistent results. Thus, the discovery of alternative or complementing biomarkers is essential; other types of circulating noncoding RNAs (ncRNAs) may also be stable and have diagnostic potential in cancer management. Long noncoding RNAs (lncRNAs) are a newly discovered class of ncRNAs that are longer than 200 nucleotides. Changes in the expression levels of lncRNAs have been increasingly reported in a variety of cancer types, suggesting a connection between

Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer

“…There have been several studies (10,16,29), including ours (9), that measure the plasma or serum lncRNAs with normalization of endogenous reference genes. b-Actin and GAPDH have been chosen as reference genes in our serum RNA measurement.…”

“…Compared with DNA, RNA directly represents the expression level of certain genes, which might significantly differ between patients with cancer and their healthy counterparts (8)(9)(10). Here, we define mRNA and lncRNA as long RNA.…”

“…Here, we define mRNA and lncRNA as long RNA. We, and other researchers, have demonstrated that some circulating long RNAs are stable in blood and have diagnostic potential in cancer management (10)(11)(12)(13)(14)(15). The diagnostic value of circulating miRNAs has been intensely investigated (16)(17)(18)(19).…”

“…Five cancerrelated mRNA diagnostic models were validated by qPCR of serum from oral squamous cell carcinoma patients (21). Circulating lncRNA urothelial cancer associated 1 (UCA1 or CUDR), long stress-induced noncoding transcript 5 (LSINCT-5), phosphatase and tensin homolog pseudogene 1 (PTENP1), and H19 in gastric cancer (10,22); metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in prostate cancer (23); and hepatocellular carcinoma upregulated lncRNA (HULC) in liver cancer (24) were found to show diagnostic value.…”

“…Circulating mRNAs were reported as effective cancer biomarkers in patients with oral cancer and breast cancer (20,21), whereas circulating lncRNAs were reported to be effective biomarkers for patients with gastric, hepatocellular, and prostatic cancer (10,14,22,23). Due to the variability in methodology in these studies, the results of these findings are inconsistent.…”