Background The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC). Methods Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature. Results The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90–8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24–6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29–0.77) and PFS (HR 0.36, 95%CI 0.21–0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort. Conclusions The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy. Trial registration A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507. Registered 3 April 2016 - Retrospectively registered.

SummaryCancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3low/SOX2high is associated with poor prognosis and could serve as an independent prognostic factor. These findings altogether indicate that MTA3/SOX2OT/SOX2 axis plays an indispensable role in CCS. Therefore, this axis could be potentially used in cancer stratification and serves as a therapeutic target.

C/EBPβ upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in CRC.

Background To analyze the correlation between the inducing effect of Fusobacterium nucleatum (Fn) on the surface expression of the inhibitory receptor KIR2DL1 on CD8 + T cells in oesophageal squamous cell carcinoma (ESCC) and the clinicopathological features and survival prognosis and to explore its clinical significance. Methods The inducing effect of Fn on CD8 + T cell surface inhibitory receptor KIR2DL1 expression was analyzed in a coculture system of human CD8 + T cells and ESCC cells infected with Fn. Fn infection and the expression of KIR2DL1 on CD8 + T cells were detected by RNAscope and immunohistochemistry in ESCC tissues, and the correlations between the inducing effect of Fn on KIR2DL1 expression on CD8 + T cells and clinicopathological features were analyzed. COX regression was used to analyze the influence of each factor on the prognosis of ESCC. Survival curves were plotted by the Kaplan–Meier method, and the effect of KIR2DL1 induction on survival time was analyzed by the log-rank test. Results In the coculture system, KIR2DL1 expression on the surface of CD8 + T cells increased with increasing Fn infection time. In ESCC tissues, Fn infection was significantly correlated with high KIR2DL1 expression on CD8 + T cells. The Fn + CD8 + KIR2DL1 positive patients were predominantly males who were smokers and alcohol drinkers. Moreover, patients with Fn infection were characterized by poor tumour differentiation, advanced clinical stage, and a short survival time. Meanwhile, Fn + CD8 + KIR2DL1 positive group was independent risk factor affecting the prognosis of ESCC patients. Conclusions Long-term drinking and smoking lead to an extremely unhealthy oral environment in which Fn infection and colonization are more likely to occur, thus inducing high expression of KIR2DL1 on the surface of CD8 + T cells, which can weaken the antitumour immune response and promote the malignant progression of ESCC. HIGHLIGHTS Fn induced high expression of KIR2DL1 CD8 + T cells in a time-dependent manner. Fn can reduce the response of tumour cells to CDDP. The inducing effect of Fn on CD8 + T cell surface KIR2DL1 expression was significantly associated with the poor prognosis of ESCC patients.