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Four plasma miRNAs act as biomarkers for diagnosis and prognosis of non-small cell lung cancer.

ABSTRACT: Previous studies have reported that the aberrant expression of circulating microRNAs (miRNAs/miRs) can be used as diagnostic and prognostic markers in non-small cell lung cancer (NSCLC). The present study aimed to assess the diagnostic and prognostic predictive values of four plasma miRNAs for NSCLC. A total of 12 candidate miRNAs were selected that have previously been reported to be aberrantly expressed in NSCLC, and their plasma levels in the training set were detected via reverse transcription-quantitative PCR analysis. The screened out miRNAs were further validated in the testing set. The area under the curve (AUC) of the receiver operating characteristic curve was constructed to evaluate diagnostic performance. Kaplan-Meier survival analysis was performed to assess the association between the plasma miRNA levels and disease-free survival (DFS) time. The results demonstrated that 4/12 plasma miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) were highly expressed in patients with NSCLC compared with their expression levels in patients with benign lung disease (BLD) and healthy controls in the training and testing sets, respectively. The AUC values of the four-miRNA panel were 0.96 and 0.93 in the training and testing sets, respectively, for distinguishing patients with NSCLC from healthy controls, which were similar to the AUC values for distinguishing patients with NSCLC from patients with BLD (0.96 and 0.94). The AUC values of the four-miRNA panel in patients with stage I NSCLC were comparable to that of patients with stage II-III NSCLC (0.942 and 0.965). Patients with high plasma levels of miR-210 and miR-150 had worse DFS than those with low plasma levels of these miRNAs. In addition, patients whose plasma levels of the four miRNAs decreased by >50% after surgery exhibited a good DFS. Taken together, the results of the present study suggest that these four miRNAs (miR-210, miR-1290, miR-150 and miR-21-5p) act as useful biomarkers for early diagnosis and prognosis of NSCLC.

SUBMITTER: Jiang HG

PROVIDER: S-EPMC8477070 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:BackgroundRadioresistance of thoracic radiotherapy is a major bottleneck in the treatment of non-small cell lung cancer (NSCLC). Until now, there have been no effective biomarkers to predict the radiosensitivity.PurposesBased on miRNA profile screened from NSCLC cell lines with different radiosensitivity, this study was conducted to explore the correlation between plasma miRNAs and radiotherapy response in NSCLC patients, and to identify biomarkers of the radiosensitivity in NSCLC.MethodsDifferentially expressed genes were acquired from time-series gene expression profiles of radioresistant H1299 and radiosensitive H460 lung cancer cells (GSE20549). Potential miRNAs were screened from these differentially expressed genes by combining bioinformatics with GO analysis, pathway analysis, and miRNA prediction. A clinical observational study was performed to explore the correlation between candidate miRNAs and radiotherapy response. Stage IIIa-IV NSCLC patients who received two to four cycles of previous chemotherapy and underwent thoracic radiotherapy alone were included. Total RNA was purified from peripheral blood before radiotherapy, and plasma miRNAs were detected by real-time PCR (qRT-PCR). Then, tumor response, progression-free survival (PFS), and overall survival (OS) were acquired. Four miRNAs significantly different between effective and ineffective groups were further analyzed to obtain cutpoints from receiver operating characteristic (ROC) curves and the predictive value of radiosensitivity.ResultsCandidate miRNAs included 14 miRNAs screened from radioresistant genes and five from radiosensitive genes. From Jan., 2013 to Dec., 2014, 54 eligible patients were enrolled with a median follow-up of 15.3 months (range 4.6 to 31.4) by the deadline of Aug. 31, 2015. Totally, there were no case of complete response (CR), 15 of partial response (PR), 35 of stable disease (SD), and 4 of progressive disease (PD). Eight patients had no progression and 19 patients were still alive. The median PFS and OS were 6.6 months (range 2.3 to 29.3) and 15.3 months (range 4.6 to 31.4), respectively. Four miRNAs (hsa-miR-98-5p, hsa-miR-302e, hsa-miR-495-3p, and hsa-miR-613) demonstrated a higher expression in effective group (CR + PR, 15 cases) than in ineffective group (SD + PD, 39 cases). Based on each cutpoint, objective response rate (ORR) was higher in miR-high group than in miR-low group. No miRNA showed correlation with median PFS or OS.ConclusionBioinformatical analysis and clinical verification reveal the correlation between plasma miRNAs and radiosensitivity in NSCLC patients. Plasma miRNAs represent novel biomarkers to predict radiotherapy response clinically.

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Four plasma miRNAs act as biomarkers for diagnosis and prognosis of non-small cell lung cancer.

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