Abstract
BackgroundHigh expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; however, its’ clinical significance and origin are unclear. We evaluated the diagnostic and prognostic value, and origin of whole blood NEAT1 in colorectal cancer.MethodsExpression of NEAT1 variants, NEAT1_v1 and NEAT1_v2 were determined using real-time quantitative PCR. The diagnostic value of whole blood NEAT1 expression was evaluated in test (n = 60) and validation (n = 200) cohorts of colorectal cancer patients and normal controls (NCs). To identify the origin of NEAT1, its expression was analyzed in blood, matched primary tumor tissues, para-tumor tissues, metastatic tissues, and also immune cells from patients or NCs. Function of NEAT1 in colorectal cell lines was also assessed. The correlation of NEAT1 expression with clinical outcomes was assessed in 191 patients.ResultsWhole blood NEAT1 expression was significantly higher in colorectal cancer patients than in NCs. NEAT1_v1 and NEAT1_v2 expression were highly accurate in distinguishing colorectal cancer patients from NCs (area under the curve: 0.787 and 0.871, respectively). Knockdown of NEAT1_v1 in vitro could inhibit cell invasion and proliferation, while knockdown of NEAT1_v2 promoted cell growth. However, whole blood expression was not correlated with matched tissues. An elevated expression was seen in neutrophils from CRC patients. Furthermore, high expression of NEAT1_v1 was correlated with worse overall survival. In contrast, high expression of NEAT1_v2 alone was correlated with better overall survival.ConclusionWhole blood NEAT1 expression is a novel diagnostic and prognostic biomarker of overall survival in colorectal cancer. Elevated NEAT1 may derive from neutrophils.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0455-5) contains supplementary material, which is available to authorized users.
Highlights
High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; its’ clinical significance and origin are unclear
Receiver operating characteristic (ROC) analysis revealed that NEAT1 expression could distinguish patients with Colorectal cancer (CRC) from Normal control (NC) (NEAT1_v1: area under the curve [Area under the curve (AUC)] = 0.732, 95 % confidence interval [CI] = 0.602–0.838; NEAT1_v2: AUC = 0.845, 95 % CI = 0.728–0.925; Fig. 1c-d)
The diagnostic value of NEAT1 was validated in a larger, independent cohort of colorectal cancer patients (n = 100) and NCs (n = 100)
Summary
High expression of the long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) in whole blood has been reported in colorectal cancer patients; its’ clinical significance and origin are unclear. LncRNAs are defined as ncRNAs longer than 200 nucleotides. They have multiple functions including acting as structural components, regulating protein trafficking, regulating transcription and cell metabolism, and modulating protein and RNA activity [6, 7]. Our former study using gene expression microarray revealed the non-protein coding RNAs (ncRNAs) – nuclearenriched Abundant Transcript 1 (NEAT1) elevated in peripheral blood from patients with CRC compared with healthy participants [8]
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