Dataset Information

Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer.

ABSTRACT: Aim:We have previously shown that the long noncoding RNA prostate cancer-associated transcript 6 (PCAT6) promoted the proliferation and invasion of lung adenocarcinoma (LUAD) cells. In this study, the diagnostic significance of tissue and serum PCAT6 was evaluated in non-small cell lung cancer (NSCLC). Materials and methods:Tissue expression of PCAT6 was systematically evaluated in five Gene Expression Omnibus datasets (GSE19804, GSE18842, GSE30219, GSE19188, and GSE27262). Circulating and tissue expressions of PCAT6 were detected by quantitative reverse-transcriptase polymerase chain reaction in NSCLC patients from Union Hospital. Results:PCAT6 was significantly increased in lung cancer tissues and could be used to distinguish LUAD from adjacent normal tissues with an area under the receiver operating characteristic curve (AUC) of 0.9210 (p<0.0001; sensitivity, 98.82%; specificity, 78.57%) in GSE30219, 0.9333 (p<0.0001; sensitivity, 86.67%; specificity, 90.77%) in GSE19188, 0.9584 (p<0.0001; sensitivity, 92.00%; specificity, 96.00%) in GSE27262, and 0.9574 (p<0.0001; sensitivity, 95.89%; specificity, 87.67%) in patients from Union Hospital. As for lung squamous cell carcinoma (LUSC), the AUC of PCAT6 was 0.9567 (p<0.0001; sensitivity, 100%; specificity, 85.71%) in GSE30219, 0.9795 (p<0.0001; sensitivity, 96.30%; specificity, 92.31%) in GSE19188, and 0.9942 (p<0.0001; sensitivity, 100%; specificity, 98.04%) in patients from Union Hospital. We further noticed that the plasma levels of PCAT6 were significantly increased in 73 LUAD and 51 LUSC patients compared with 39 healthy controls (p<0.0001). The AUC of circulating PCAT6 was 0.9213 (p<0.0001; sensitivity, 87.67%; specificity, 97.44%) in LUAD and 0.9583 (p<0.0001; sensitivity, 94.12%; specificity, 100%) in LUSC. Conclusion:Together with our previous findings, our results suggest that PCAT6 could be used as a potential diagnostic and prognostic biomarker in NSCLC.

SUBMITTER: Wan L

PROVIDER: S-EPMC5713690 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer.

Wan Li L Zhang Lin L Fan Kai K Wang Jian-Jun JJ

OncoTargets and therapy 20171128

<h4>Aim</h4>We have previously shown that the long noncoding RNA prostate cancer-associated transcript 6 (PCAT6) promoted the proliferation and invasion of lung adenocarcinoma (LUAD) cells. In this study, the diagnostic significance of tissue and serum PCAT6 was evaluated in non-small cell lung cancer (NSCLC).<h4>Materials and methods</h4>Tissue expression of PCAT6 was systematically evaluated in five Gene Expression Omnibus datasets (GSE19804, GSE18842, GSE30219, GSE19188, and GSE27262). Circul ...[more]

PMID: 29238201

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Project description:BACKGROUND:NSCLC (non-small-cell lung cancer) is the leading cause of cancer-related mortality worldwide. Both epigenetic and genetic changes contribute to the initiation, development and metastasis of NSCLC. Recently, accumulating data have begun to support the notion that long noncoding RNAs (lncRNAs) function as new crucial regulators of diverse biological processes, including proliferation, apoptosis and metastasis, and play crucial roles in tumorigenesis. Nevertheless, further study is warranted to comprehensively determine lncRNAs' functions and potential mechanism. METHODS:In this study, we performed a comprehensive analysis of the lncRNA expression profile of NSCLC using data from TCGA and Gene Expression Omnibus (GEO). PCAT6 expression level in a cohort of 60 pairs of NSCLC tissues using quantitative real-time PCR (qRT-PCR). Additionally, Loss-of-function assays and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. Tumor formation assay in a nude mouse model was performed to verity the role of PCAT6 in NSCLC in vivo. Meanwhile, RIP, ChIP, resue experiment and western blot assays were used to highlights the potential molecular mechanism of PCAT6 in NSCLC. FINDINGS:We identified that an oncogene, PCAT6, was upregulated in NSCLC, and this upregulation was verified in a cohort of 60 pairs of NSCLC tissues. Additionally, the expression level of PCAT6 was correlated with tumor size (P =?.036), lymph node metastasis (P?=?.029) and TNM stage (P?=?.038). Loss-of-function and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. The results revealed that PCAT6 knockdown mitigated NSCLC cell growth by inducing G1-phase cell cycle arrest and apoptosis in vitro and in vivo. Whereas, PCAT6 overexpression could promoted tumor cell growth. Meanwhile, PCAT6 additionally promoted NSCLC cell migration and invasion. Furthermore, mechanistic investigation demonstrated that the oncogenic activity of PCAT6 is partially attributable to its repression of LATS2 via association with the epigenetic repressor EZH2 (Enhancer of zeste homolog 2). Overall, our study highlights the essential role of PCAT6 in NSCLC, suggesting that PCAT6 might be a potent therapeutic target for patients with NSCLC.

Project description:Lung cancer is the first leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence shows that long noncoding RNA (lncRNA) are capable of modulating tumor initiation, proliferation and metastasis. In the present study, we aimed to evaluate whether circulating lncRNA could be used as biomarkers for diagnosis and prognosis of NSCLC. Expression profiles of 14 lncRNA selected from other studies were validated in 20 pairs of tissues by quantitative real-time PCR, and the dysregulated lncRNA thus identified were further validated in serum samples from two independent cohorts along with three tumor makers (CEA, CYFRA21-1, and SCCA). Receiver-operating characteristic analysis was utilized to estimate the diagnostic efficiency of the candidate lncRNA and tumor markers. Importantly, we observed an association between lncRNA expression and overall survival (OS) rate of NSCLC. The expressions of SOX2 overlapping transcript (SOX2OT) and ANRIL were obviously upregulated in NSCLC tissues and serum samples compared with normal controls (P < 0.01). Based on the data from the training set, we next used a logistic regression model to construct an NSCLC diagnostic panel consisting of two lncRNA and three tumor markers. The area under the curve of this panel was 0.853 (95% confidence interval = 0.804-0.894, sensitivity = 77.1%, specificity = 79.2%), and this was distinctly superior to any biomarker alone (all at P < 0.05). Similar results were observed in the validation set. Intriguingly, Kaplan-Meier analysis demonstrated that low expressions of SOX2OT and ANRIL were both associated with higher OS rate (P = 0.008 and 0.017, respectively), and SOX2OT could be used as an independent prognostic factor (P = 0.036). Taken together, our study demonstrated that the newly developed diagnostic panel consisting of SOX2OT, ANRIL, CEA, CYFRA21-1, and SCCA could be valuable in NSCLC diagnosis. LncRNA SOX2OT and ANRIL might be ideal biomarkers for NSCLC prognosis.

Project description:BackgroundAlthough expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in tumor tissues has been assessed in several malignancies. However, the association between lncRNA MALAT-1 expression and prognosis or clinicopathological feature remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA MALAT-1 expression was associated with prognosis or clinicopathological features in patients with non-small cell lung cancer (NSCLC).MethodsWe searched Embase, PubMed, Web of Science, Cochrane library, The Chinese National Knowledge Infrastructure, and Wanfang databases from inception to March, 1, 2020. The language restrictions were Chinese and English. The published literature on lncRNA MALAT-l expression and prognosis or clinicopathological characteristics of NSCLC patients was statistically analyzed. Combined hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were used to evaluate the effects of lncRNA MALAT-l on the prognosis and clinicopathological features of NSCLC.ResultsFifteen studies with 1477 NSCLC patients were enrolled. The results showed that the elevated expression of lncRNA MALAT-l in tumor tissues was associated with shorter overall survival (OS) (HR: 2.20, 95% CI: 1.53-3.16; P = 0.000). Additionally, high lncRNA MALAT-l expression was also significantly associated with gender (OR: 0.69, 95% CI: 0.51-0.93; P = 0.014), tumor size (OR: 1.87, 95% CI:1.13-3.09; P = 0.016), lymph node metastasis (LNM) (OR: 2.87, 95% CI:1.05-7.83, P = 0.04), tumor differentiation (OR: 1.60, 95% CI:1.17-2.20; P = 0.003), and tumor-node-metastasis (TNM) stage (OR: 0.42, 95% CI: 0.25-0.70; P = 0.001). There was no significant relationship between lncRNA MALAT-l expression and other clinicopathological features including age (OR: 1.03, 95% CI: 0.79-1.34; P = 0.830), number of tumors (OR: 1.02, 95% CI: 0.63-1.64; P = 0.943), vascular invasion (OR: 1.23, 95% CI: 0.50-3.05; P = 0.652), and recurrence (OR: 1.98, 95% CI: 0.67-5.85; P = 0.214).ConclusionThe overexpression of lncRNA MALAT-l in NSCLC tissues was correlated with OS, gender, tumor size, LNM, tumor differentiation, and TNM stage. Thus, lncRNA MALAT-l may serve as a prognostic factor for NSCLC.

Dataset Information

Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer.

Publications

Diagnostic significance of circulating long noncoding RNA PCAT6 in patients with non-small cell lung cancer.

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