Characterization of progression-related alternative splicing events in testicular germ cell tumors.

Accumulating evidence supports the significance of aberrant alternative splicing (AS) events in cancer; however, genome-wide profiling of progression-free survival (PFS)-related AS events in testicular germ cell tumors (TGCT) has not been reported. Here, we analyzed high-throughput RNA-sequencing data and percent-spliced-in values for 150 patients with TGCT. Using univariate and multivariate Cox regression analysis and a least absolute shrinkage and selection operator method, we identified the top 15 AS events most closely associated with disease progression. A risk-associated AS score (ASS) for the 15 AS events was calculated for each patient. ASS, pathological stage, and T stage were significantly associated with disease progression by univariate analysis, but only ASS and pathological stage remained significant by multivariate analysis. The ability of these variables to predict 5-year progression was assessed using receiver operating characteristic curve analysis. ASS had stronger predictive value than a combination of age, pathological stage, and T stage (area under the curve = 0.899 and 0.715, respectively). Furthermore, Kaplan-Meier analysis of patients with low and high ASS demonstrated that high ASS was associated with significantly worse PFS than low ASS (P = 1.46 × 10-7). We also analyzed the biological functions of the PFS-related AS-related genes and found enrichment in pathways associated with DNA repair and modification. Finally, we identified a regulatory network of splicing factors with expression levels that correlated significantly with AS events in TGCT. Collectively, this study identifies a novel method for risk stratification of patients and provides insight into the molecular events underlying TGCT.

[Impacts of shading on seedling growth and mineral accumulation in Paeonia lactiflora]. / é®è«å¤„ç†å¯¹èŠè¯å¹¼è‹—ç”Ÿé•¿å’ŒçŸ¿è´¨è¥å »ç§¯ç´¯çš„å½±å“.

Shading is one of the important strategies to protect seedlings of Paeonia lactiflora. The effects of shading treatments on seedling growth and mineral accumulation of Duolun P. lactiflora were investigated in a greenhouse experiment to provide guidance for P. lactiflora cultivation. One week after emergence, seedlings were treated with 20%, 40%, 60% or 80% shading for two months, with no-shading as the control (CK). The results showed that shading treatments significantly increased plant height by 19.9%, 31.1%, 52.9%, and 63.7%, respectively. However, shading significantly reduced the root mass ratio and root to shoot ratio by 21.5%, 23.6%, 29.2%, 41.8% and 40.6%, 44.0%, 50.9%, 63.2%, respectively. Moreover, 40%, 60% and 80% shading significantly increased specific leaf area by 77.0%, 84.1% and 65.2%, and significantly increased chlorophyll content by 92.3%, 128.7%, 98.1%, and increased carotenoid content by 86.9%, 113.1% and 90.5%, respectively. The treatments of 40%, 60%, and 80% shading significantly decreased root biomass by 61.4%, 74.3% and 78.6%, respectively. Compared with CK, 20%, 40% and 80% shading, the 60% shading treatment increased root phosphorus content by 245.7%, 65.9%, 40.5% and 10.3%, increased potassium content by 102.9%, 131.7%, 57.0%, 63.3% and magnesium content by 131.3%, 55.1%, 40.4%, 7.7%, respectively. 60% shading was an appropriate shading intensity for P. lactiflora seedling cultivation based on local conditions in Duolun.

PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy.

BACKGROUND: Protein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently been in the spotlight as a tumor suppressor, whose encoding gene is frequently methylated in cancers. We examined the methylation status of the PTPRO gene promoter in breast cancer and evaluated the correlation between PTPRO promoter methylation and both clinicopathological parameters and prognosis of breast cancer patients. METHODS: Two hundred twenty-one formalin-fixed, paraffin-embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched plasma samples, collected from primary breast cancer patients, were assessed for PTPRO gene promoter methylation using methylation-specific PCR. Associations of promoter methylation with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect on survival. RESULTS: 175 samples gave identifiable PCR products, of which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation correlated with higher histological grade (P = 0.028), but not other clinical parameters. Multivariate analysis indicated that overall survival (OS) was significantly poorer in HER2-positive, but not ER-positive patients with methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and only observed in plasma from patients whose corresponding primary tumors were also methylated. CONCLUSIONS: PTPRO methylation is a common event in the primary breast cancer and can be reliably detected in peripheral blood samples. PTPRO methylation is associated with poor survival only in HER2-positive patients, suggesting use of PTPRO methylation as a prognostic factor for breast cancer and for optimizing individualized therapy for HER2-positive patients.