A novel urinary long non‐coding RNA transcript improves diagnostic accuracy in patients undergoing prostate biopsy

Jia

et al. 2018

Cell Physiol Biochem

Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

Section: Introductionmentioning

confidence: 99%

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

Jia

et al. 2018

Cell Physiol Biochem

“…Given the altered expression of lncAPP in advanced PCa, we hypothesized a potential relationship with clinical outcomes. Our previous study demonstrated that circulating lncRNAs could exist in a stable form of fragments and urine sediments derived lncRNAs could be used as diagnostic marker of PCa . To examine whether lncAPP could be present in extracellular fluid, we extracted RNAs in urine sediments of PCa patients.…”

Section: Resultsmentioning

confidence: 99%

The previously uncharacterized lncRNA APP promotes prostate cancer progression by acting as a competing endogenous RNA

Shi

Zhang

Nian

et al. 2019

Intl Journal of Cancer

Self Cite

Long noncoding RNAs (lncRNAs) promote cell proliferation, migration, invasion and castration resistance in prostate cancer (PCa). Understanding the inherited molecular mechanisms by which lncRNAs contribute to the progression of PCa to a lethal disease could have an important impact on cancer detection, diagnosis and prognosis. In our study, PCa‐associated lncRNA transcripts from RNA‐seq data were identified and screened via bioinformatics analysis, NCBI annotations and literature review. We identified a novel lncRNA, lncAPP (lncRNA activated in PCa progression), which activates in PCa progression and is expressed in primary tumor tissues and urine samples of patients with localized or advanced PCa. Urinary‐based lncAPP is a promising biomarker for predicting PCa progression. In vitro and in vivo studies demonstrated that lncAPP enhanced cell proliferation and promoted migration and invasion. The underlying mechanism of lncRNA was investigated by RNA immunoprecipitation, dual‐luciferase reporter system assay, etc. Upregulation of lncAPP promoted cell migration and invasion via competitively binding miR218 to facilitate ZEB2/CDH2 expression. In addition, in vivo subcutaneous tumor xenograft models and tail intravenously injection metastatic models were constructed to evaluate lncRNA function. Targeting lncAPP/miR218 axis in cell lines and tumor xenografts restrained tumor progression properties both in vitro and in vivo. These results establish that lncAPP/miR218 axis plays a critical role in PCa progression, and they also suggest new strategies to prevent tumor progression for therapeutic purposes.

“…Furthermore, lncRNAs have been not only studied in tumor tissue but have also been identified in the circulation in an increasing number of other cancers. For example, the lncRNA FR0348383 in urine improved diagnostic accuracy in patients undergoing prostate biopsy [19], FER1L4 was demonstrated to be present in human plasma and to be significantly down-regulated after surgery [20], and AA174084 was reported to have potential as a marker for early diagnosis of gastric cancer [21]. Although no systematic study has examined circulating lncRNAs in CRC patients, miRNAs, another class of non-coding RNA, have been widely studied in the circulation of CRC patients [22].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNAs LOC285194, RP11-462C24.1 and Nbla12061 in serum provide a new approach for distinguishing patients with colorectal cancer from healthy controls

Han

et al. 2016

Oncotarget

Colorectal cancer (CRC) is currently the most prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for CRC screening. Accumulating evidence reveals that long non-coding RNAs (lncRNAs) detectable in serum are associated with the genesis and development of various types of cancer. Therefore, we examined the diagnostic ability of lncRNAs in blood samples from patients with CRC by evaluating the levels of 17 CRC- or gastrointestinal cancer-related lncRNAs in serum samples from 71 CRC patients and 70 healthy individuals using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We detected 13 lncRNAs in serum, three of which displayed significantly different levels between CRC patients and healthy controls. A three-lncRNA signature (LOC285194, RP11-462C24.1 and Nbla12061) identified via stepwise regression analysis showed potential as a diagnostic marker for CRC. The area under the receiver operating characteristic curve of this signature for distinguishing CRC patients from healthy individuals was 0.793 (95% CI: 0.709 to 0.861). The diagnostic ability of this marker was much higher than that of conventional blood biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125) and carbohydrate antigen 724 (CA724). Combining this novel marker with conventional biomarkers produced even greater diagnostic ability. Furthermore, the levels of the three lncRNAs decreased after the patients underwent surgical resection. The results of this study suggest an additional marker for CRC screening and provide new directions for further investigation.