Edited by Zhijie ChangMineralizing osteoblasts (MOBs) can release exosomes, although the functional significance remains unclear. In the present study, we demonstrate that exosomes derived from mineralizing pre-osteoblast MC3T3-E1 cells can promote bone marrow stromal cell (ST2) differentiation to osteoblasts. We reveal that MOB-derived exosomes significantly influence miRNA profiles in recipient ST2 cells, and these changes tend to activate the Wnt signaling pathway by inhibiting Axin1 expression and increasing b-catenin expression. We also suggest that MOB derived-exosomes partly induce the variation in miRNA expression in recipient ST2 cells by exosomal miRNA transfer. These findings suggest an exosome-mediated mode of cell-to-cell communication in the osteogenic microenvironment, and also indicate the potential of MOB exosomes in bone tissue engineering.

To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

Background: There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells.

Small cell lung cancer (SCLC), as a proportion, makes up only 15–17% of lung cancer cases. The development of treatments for SCLC has remained stagnant for decades, and SCLC is expected to persist as a threat to human health. To date, no publications based on large populations have been reported. We calculated survival changes in patients with SCLC during each decade between 1983 and 2012 to determine the roles of race, sex, age, and socioeconomic status (SES) on survival rates based on the Surveillance, Epidemiology, and End Results (SEER) registries. In total, 106,296 patients with SCLC were identified, with the overall incidence per 100,000 decreasing each decade from 9.6 to 7.8 to 5.8. The median survival for SCLC remained 7 months, and the 12-month relative survival rates (RSRs) remained relatively stable at 32.9%, 33.2% and 33.2% during each decade. The 5-year RSRs significantly improved from 4.9% to 5.9% to 6.4% during each decade, but remained extremely low. In addition, a narrowing of the survival gaps among SES groups and stable survival gaps between sexes were observed. Although the incidence of SCLC decreased during each decade, the overall survival remained relatively stable, highlighting the urgency of developing novel treatments and the importance of prevention and early detection.

Background: Long noncoding RNA (lncRNA) and mRNAs are long RNAs (!200 nucleotides) compared with miRNAs. In blood, long RNAs may be protected by serum extracellular vesicles, such as apoptotic bodies (AB), microvesicles (MV), and exosomes (EXO). They are potential biomarkers for identifying cancer.Methods: Sera from 76 preoperative colorectal cancer patients, 76 age-and sex-matched healthy subjects, and 20 colorectal adenoma patients without colorectal cancer were collected. We investigated the distribution of long RNAs into the three vesicles. Seventy-nine cancer-related long RNAs were chosen and detected using qPCR.Results: The quantity of long RNA has varying distribution among three subtypes of extracellular vesicles in serum. Most mRNA and lncRNA genes had higher quantity in EXOs than that

BackgroundValidity of self-reported height and weight has not been adequately evaluated in diverse adolescent populations. In fact there are no reported validity studies conducted in Asian children and adolescents. This study aims to examine the accuracy of self-reported weight, height, and resultant BMI values in Chinese adolescents, and of the adolescents' subsequent classification into overweight categories.MethodsWeight and height were self-reported and measured in 1761 adolescents aged 12-16 years in a cross-sectional survey in Xi'an city, China. BMI was calculated from both reported values and measured values. Bland-Altman plots with 95% limits of agreement, Pearson's correlation and Kappa statistics were calculated to assess the agreement.ResultsThe 95% limits of agreement were -11.16 and 6.46 kg for weight, -4.73 and 7.45 cm for height, and -4.93 and 2.47 kg/m2 for BMI. Pearson correlation between measured and self-reported values was 0.912 for weight, 0.935 for height and 0.809 for BMI. Weighted Kappa was 0.859 for weight, 0.906 for height and 0.754 for BMI. Sensitivity for detecting overweight (includes obese) in adolescents was 56.1%, and specificity was 98.6%. Subjects' area of residence, age and BMI were significant factors associated with the errors in self-reporting weight, height and relative BMI.ConclusionsReported weight and height does not have an acceptable agreement with measured data. Therefore, we do not recommend the application of self-reported weight and height to screen for overweight adolescents in China. Alternatively, self-reported data could be considered for use, with caution, in surveillance systems and epidemiology studies.

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