BackgroundMany long non-coding RNAs(lncRNAs) have been found to be a good marker for several tumors. Using lncRNA-mining approach, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival.MethodsWe performed LncRNA expression profiling in 887 breast cancer patients from Gene Expression Omnibus (GEO) datasets. The association between lncRNA signature and clinical survival was analyzed using the training set(n = 327, from GSE 20685). The validation for the association was performed in another three independent testing sets(252 from GSE21653, 204 from GSE12276, and 104 from GSE42568).ResultsA set of four lncRNA genes (U79277, AK024118, BC040204, AK000974) have been identified by the random survival forest algorithm. Using a risk score based on the expression signature of these lncRNAs, we separated the patients into low-risk and high-risk groups with significantly different survival times in the training set. This signature was validated in the other three cohorts. Further study revealed that the four-lncRNA expression signature was independent of age and subtype. Gene Set Enrichment Analysis (GSEA) suggested that gene sets were involved in several cancer metastasis related pathways.ConclusionsThese findings indicate that lncRNAs may be implicated in breast cancer pathogenesis. The four-lncRNA signature may have clinical implications in the selection of high-risk patients for adjuvant therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-014-0084-7) contains supplementary material, which is available to authorized users.

Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T-cell response through the induction of T-cell anergy and the development of Treg in tumor-bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic.

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This is the first meta-analysis investigating the relationship between NAFLD and CVD independent of the impact of DM. Our findings suggested that NAFLD increases the risk of CVD in populations with comparable DM profiles. Diabetic patients diagnosed with NAFLD might benefit from a more early cardiovascular risk assessment, thereby reducing CVD morbidity and mortality.

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta‐analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random‐effects model. We used the Newcastle‐Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta‐analysis. The Newcastle‐Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non‐NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45‐1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima‐media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47‐2.06), 1.56 (1.24‐1.96), 1.40 (1.22‐1.60), and 3.73 (0.99‐14.09), respectively. Conclusion: Our meta‐analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376‐392)