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Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) still has a poor prognosis. The prognostic biomarkers of ESCC are not yet well established. Long noncoding RNAs (lncRNAs) have recently been intensively investigated in various cancers including ESCC, and are found to be closely correlated to ESCC. Dysregulated expression of lncRNAs was widely observed in ESCC tumor tissue and was closely related to the tumorigenesis and progression of ESCC. More and more studies have found that lncRNAs were significantly correlated with the prognosis and diagnosis of patients with ESCC. Therefore, all those accumulating evidence indicated that lncRNAs could serve as a prognostic biomarker of ESCC. In this, we summarized the relation between lncRNAs and ESCC as well as the potential biomarker role of lncRNAs in ESCC, especially the prognostic value of lncRNAs. Our current review highlighted the need of further studies to explore the biomarker functions as well as therapeutic values of lncRNAs in ESCC.

SUBMITTER: Deng HY

PROVIDER: S-EPMC4999701 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

Deng Han-Yu HY Wang Yun-Cang YC Ni Peng-Zhi PZ Lin Yi-Dan YD Chen Long-Qi LQ

Journal of thoracic disease 20160801 8

Esophageal squamous cell carcinoma (ESCC) still has a poor prognosis. The prognostic biomarkers of ESCC are not yet well established. Long noncoding RNAs (lncRNAs) have recently been intensively investigated in various cancers including ESCC, and are found to be closely correlated to ESCC. Dysregulated expression of lncRNAs was widely observed in ESCC tumor tissue and was closely related to the tumorigenesis and progression of ESCC. More and more studies have found that lncRNAs were significantl ...[more]

PMID: 27621894

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Project description:Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to stratify patients by molecular subtype, thus aiding personalized treatments.

Project description:Ovarian cancer (OC) is a highly malignant gynecologic tumor with few treatments available and poor prognosis with the currently available diagnostic markers and interventions. More effective methods for diagnosis and treatment are urgently needed. Although the current evidence implicates ferroptosis in the development and therapeutic responses of various types of tumors, it is unclear to what extent ferroptosis affects OC. To explore the potential of ferroptosis-related genes as biomarkers and molecular targets for OC diagnosis and intervention, this study collected several datasets from The Cancer Genome Atlas-OC (TCGA-OC), analyzed and identified the coexpression profiles of 60 ferroptosis-related genes and two subtypes of OC with respect to ferroptosis and further examined and analyzed the differentially expressed genes between the two subtypes. The results indicated that the expression levels of ferroptosis genes were significantly correlated with prognosis in patients with OC. Single-factor Cox and LASSO analysis identified eight lncRNAs from the screened ferroptosis-related genes, including lncRNAs RP11-443B7.3, RP5-1028K7.2, TRAM2-AS1, AC073283.4, RP11-486G15.2, RP11-95H3.1, RP11-958F21.1, and AC006129.1. A risk scoring model was constructed from the ferroptosis-related lncRNAs and showed good performance in the evaluation of OC patient prognosis. The high- and low-risk groups based on tumor scores presented obvious differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration, indicating that the risk score has a good ability to predict the benefit of immunotherapy and may provide data to support the implementation of precise immunotherapy for OC. Although in vivo tests and research are needed in the future, our bioinformatics analysis powerfully supported the effectiveness of the risk signature of ferroptosis-related lncRNAs for prognosis prediction in OC. The findings suggest that these eight identified lncRNAs have great potential for development as diagnostic markers and intervention targets for OC and that patients with high ferroptosis-related lncRNA expression will receive greater benefits from conventional chemotherapy or treatment with ferroptosis inducers.

Project description:BackgroundAll cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene's pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC.MethodsFor this study, we used biopsy from the Imam Khomeini Cancer Institute's tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses.ResultsComparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn't associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins.ConclusionThis is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them.

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Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

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Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

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