BackgroundOesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles.ObjectiveTo assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs.MethodLncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis.ResultsLncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages.ConclusionsOur results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

Introduction: Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. Methods: Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomographycomputed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726). Results: A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p ¼ 0.0471).

Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients’ postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.

microRNAs (miRNAs) regulate gene expression at the posttranscriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the upregulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer deaths worldwide. The incidence of esophageal cancer varies greatly by geographic location, where it is most common in China, Southeast Africa, and Japan. Compared with the high incidence of Barrett's associated adenocarcinoma in Europe and the United States (1), the incidence of esophageal squamous cell carcinoma (ESCC) 3 is prevalent in China. Despite the advances in therapy, ESCC is still one of the most lethal malignancies in China, with an overall 5-year survival rate of 20 -30% after surgery (2, 3). Tumor metastasis is primarily responsible for ESCC mortality, yet the molecular mechanism of metastatic dissemination remains unclear (4). Recent evidences suggest that miRNAs play an important role in tumor metastasis (5-8). miRNA is the noncoding RNA of ϳ22 nucleotides that regulates gene expression via degradation of target mRNAs or inhibition of protein translation. Hundreds of miRNAs have been identified, and some of them exhibit highly specific expression patterns in various tissues and species. More than 50% of annotated human miRNA genes are located in fragile chromosomal regions that are susceptible to amplification, deletion or translocation during the process of tumor development and can function either as oncogene or tumor suppressor (9). miR-92a belongs to the miR-17-92a cluster and is located on chromosome 13q32-33, a region frequently amplified in B-cell lymphoma (10, 11), lung cancer (12), and colorectal cancer (13). The polycistronic miR-17-92a cluster produces six mature miRNAs (miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1). Up-regulation of these miRNAs were found in B-cell...

BackgroundThe effect of sleep duration on cancer risk remains controversial. We aimed to quantify the available evidence on this relationship using categorical and dose–response meta-analyses.MethodsPopulation-based cohort studies and case-control studies with at least three categories of sleep duration were identified by searching PubMed, EMBASE, and the Cochrane Library database up to July 2017.ResultsSixty-five studies from 25 articles were included, involving 1,550,524 participants and 86,201 cancer cases. The categorical meta-analysis revealed that neither short nor long sleep duration was associated with increased cancer risk (short: odds ratio [OR] = 1.01, 95% confidence intervals [CI] = 0.97–1.05; long: OR = 1.02, 95% CI = 0.97–1.07). Subgroup analysis revealed that short sleep duration was associated with cancer risk among Asians (OR = 1.36; 95% CI: 1.02–1.80) and long sleep duration significantly increased the risk of colorectal cancer (OR = 1.21; 95% CI: 1.08–1.34). The dose–response meta-analysis showed no significant relationship between sleep duration and cancer risk. When treated as two linear piecewise functions with a cut point of 7 h, similar nonsignificant associations were found (per 1-h reduction: OR = 1.02, 95% CI = 0.98–1.07; per 1-h increment: OR = 1.003, 95% CI = 0.97–1.03).ConclusionCategorical meta-analysis indicated that short sleep duration increased cancer risk in Asians and long sleep duration increased the risk of colorectal cancer, but these findings were not consistent in the dose–response meta-analysis. Long-term randomized controlled trials and well-designed prospective studies are needed to establish causality and to elucidate the mechanism underlying the association between sleep duration and cancer risk.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5025-y) contains supplementary material, which is available to authorized users.