BackgroundRecent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC.MethodsTen lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC.ResultsESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%).ConclusionsPlasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-14-3) contains supplementary material, which is available to authorized users.

BackgroundThere is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated.MethodsIn total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival.ResultsApplying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158–2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032–1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113–3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481–2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448–2.585; p < 0.001) were independently correlated with overall survival.ConclusionsThis study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.

BackgroundExpression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients.MethodsThe method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed.ResultsLOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002).ConclusionDecreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.