Berry texture QTL and candidate gene analysis in grape (Vitis vinifera L.).

Berry texture is a noteworthy economic trait for grape; however, the genetic bases and the complex gene expression and regulatory mechanism for the diverse changes in berry texture are still poorly understood. In this study, the results suggest that it is difficult to obtain high-mesocarp firmness (MesF) and high-pericarp puncture hardness (PPH) grape cultivars with high pericarp brittleness (PerB). The high-density linkage map was constructed using whole-genome resequencing based on 151 F1 individuals originating from intraspecific hybridization between the firm-flesh cultivar 'Red Globe' and soft-flesh cultivar 'Muscat Hamburg'. The total length of the consensus map was 1613.17 cM, with a mean genetic distance between adjacent bin markers of 0.59 cM. Twenty-seven quantitative trait loci (QTLs) for berry MesF, PPH, and PerB were identified in linkage groups (LGs) 1, 3, 4, 6, 8, 9, 10, 11, 14, 16, and 17, including twelve QTLs that were firstly detected in LGs 6, 11, and 14. Fourteen promising candidate genes were identified from the stable QTL regions in LGs 10, 11, 14, and 17. In particular, VvWARK2 and VvWARK8 refer to chromosome 17 and are two promising candidate genes for MesF and PPH, as the VvWARK8 gene may increase pectin residue binding with WARK for high berry firmness maintenance and the allele for VvWARK2 carrying the 'CC' and 'GA' genotypes at Chr17:1836764 and Chr17:1836770 may be associated with non-hard texture grape cultivars. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) verification revealed that the promising candidate transcription factor genes VvMYB4-like, VvERF113, VvWRKY31, VvWRKY1, and VvNAC83 may regulate cell wall metabolism candidate gene expression for grape berry texture changes.

ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer.

The infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein-protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma.

OBJECTIVES: The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. METHODS: The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein-protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. RESULTS: The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. CONCLUSIONS: The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

Overexpression and clinical significance of IBP in epithelial ovarian carcinoma.

Interferon regulatory factor-4 binding protein (IBP) is as a type of ρ GTPase suggested to serve an important role in tumor occurrence and development through the effects of cytoskeletal remodeling, and cell conduction mechanism. IBP is widely expressed in the immune system and expressed in several types of tumors. However, its expression and prognostic value in epithelial ovarian carcinoma (EOC) remain unclear. The present study aimed to investigate the expression of IBP in EOC, and its effect on clinicopathological variables and prognosis. A total of 107 and 30 cases of epithelial ovarian carcinoma and benign ovarian disease tissue sections, respectively, were examined using immunohistochemistry. The results indicated that the IBP expression status was negative or markedly weak in normal tissues, but highly expressed in EOC tissues. A significant association was observed between IBP overexpression and various clinicopathological factors, including advanced International Federation of Gynecology and Obstetrics stage (P<0.001), poor histologic grade (P=0.002), peritoneal carcinomatosis (P<0.001), lymph-node metastasis (P=0.023) and recurrence (P<0.001). Multivariate Cox regression analysis additionally suggested that IBP overexpression was an independent factor affecting recurrence-free survival [hazard ratio (HR)=4.099; 95% confidence interval (CI), 2.209-7.606; P<0.001) and overall survival (HR=2.317; 95% CI, 1.484-3.617; P<0.001) in patients with EOC. The results of the present study demonstrated that IBP overexpression may be associated with tumor development and progression in EOC, and therefore may serve as a novel target for treating this disease.