The expression profile of Gasdermin C-related genes predicts the prognosis and immunotherapy response of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis and is relatively unresponsive to immunotherapy. Gasdermin C (GSDMC) induces pyroptosis in cancer cells and inflammation in the tumor microenvironment. However, whether GSDMC expression in PAAD is associated with survival or response to immunotherapy remains unknown. GSDMC expression and the relationship between GSDMC and patient survival or immune infiltration in PAAD were examined using data in the The Cancer Genome Atlas (TCGA), Gene Expression Ominbus (GEO), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) databases. The TCGA PAAD cohort could be divided into two distinct risk groups based on the expression of GSDMC-related genes (GRGs). The TIDE algorithm predicted that the low-risk group was more responsive to immune checkpoint blockade therapy than the high-risk group. A novel 15-gene signature was constructed and could predict the prognosis of PAAD. In addition, the 15-gene signature model predicted the infiltration of immune cells and Immune checkpoint blockade (ICB) treatment response. Immunohistochemical staining assessment of patient-derived human tissue microarray (TMA) from 139 cases of local PAAD patients revealed a positive correlation between GSDMC expression and PD-L1 expression but a negative correlation between GSDMC expression and infiltration of low CD8+ T cells. Moreover, the overexpression of GSDMC was related to poor overall survival (OS). This study suggests that GSDMC is a valuable biomarker for predicting PAAD prognosis and predicts the immunotherapy response of PAAD.

Effect of Nutrient Addition on the Productivity and Species Richness of Grassland Along With an Elevational Gradient in Tajikistan.

Grasslands provide key resource for the millions of people who are dependent on livestock in Tajikistan. Productivity and species richness (SR) are important characteristics of grassland ecosystems and are greatly affected by nutrient inputs. The effect that climate change might have on these characteristics remains unclear. Here, an in situ nitrogen (N) and phosphorus (P) fertilization experiment was conducted at four sites along with an elevational gradient (650, 1,100, 1,250, and 2,000 m) in western Tajikistan over 2 years (2018 and 2019) to examine the influences of nutrient availability and climate change on aboveground biomass (AGB) and SR; precipitation and temperature were also considered to analyze the responses. It demonstrated that enrichment with N, P, and their combinations significantly increased AGB along with an elevational gradient (p < 0.05). AGB increased as the concentrations of nutrients added increased. The maximum AGB, which was 2-fold higher compared with control, was observed when 90 kg N ha-1year-1 and 30 kg P ha-1year-1 were added. In addition, nitrogen addition alone stimulated greater AGB than P addition, although no significant difference was observed between these two treatments. Enrichment with N, P, and their combination had no significant effect on SR; however, SR significantly changed at different elevation. Elevation had direct effect on precipitation and temperature, which, in turn, resulted in variation in AGB and SR. Moreover, both nutrient and elevation had significant effect on AGB and SR, but there was no interaction effect of them. AGB and SR interacted with significant negative correlation. In the high-elevation area, plants grew better in the warmer year (2018); this indicates that grasslands in high mountain areas in Tajikistan might have higher productivity as the climate warms, which will positively affect the economic development of the country.

miR-340 and ZEB1 negative feedback loop regulates TGF-ß- mediated breast cancer progression.

MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3'-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-ß-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression.

Number of negative lymph nodes as a prognostic factor for ypN0-N1 breast cancer patients undergoing neoadjuvant chemotherapy.

Some of node-positive patients could have a pathologically complete response in terms of lymph nodes. For these patients, the number of negative lymph nodes (NLNs) may be higher than that in the same-stage patients who initially received mastectomy. After neoadjuvant chemotherapy (NAC), the following treatment especially the postmastectomy radiotherapy (PMRT) is controversial for ypN1 (with one to three positive lymph nodes after NAC) patients. A total of 289 patients who received NAC from 2006 to 2009 were included in the investigation. The prognostic value of the number of NLNs on these patients was analyzed. Besides, we analyzed if the number of NLNs would give some indications on PMRT in ypN1 patients. The follow-up of all the patients began the first chemotherapy on 15 March 2015. The 5-year disease-free survival (DFS) and overall survival (OS) rates were determined as 67.2 and 81.1 %, respectively. The number of NLNs was associated with primary stage (p < 0.001), pathological tumor size (p < 0.05), pathological nodal stage (p < 0.001), and pathological stage after NAC (p < 0.001). The univariate and multivariate analyses revealed that the number of NLNs is an independent prognostic factor in both DFS and OS. In ypN0-N1 stage, patients with >13 NLNs had better DFS (p < 0.001) and OS (p < 0.001) than the patients with ≤13 NLNs. Although the fact patients in ypN2-N3 stage with >13 NLNs had better DFS and OS than the others, there were no significant statistical difference. In the subgroup analysis, PMRT improved the OS (p < 0.05) and DFS (p < 0.05) of ypN1 patients with ≤13 NLNs. The number of NLNs is a prognostic indicator in ypN0-N1 patients. Patients in ypN1 stage with less number of NLNs will benefit from PMRT.

Serum deprivation response inhibits breast cancer progression by blocking transforming growth factor-ß signaling.

Serum deprivation response (SDPR), a key substrate for protein kinase C, play a critical role in inducing membrane curvature and participate in the formation of caveolae. However, the function of SDPR in cancer development and progression is still not clear. Here, we found that SDPR is downregulated in human breast cancer. Overexpression of SDPR suppresses cell proliferation and invasion in MDA-MB-231 cells, while depletion of SDPR promotes cell proliferation and invasion in MCF10A cells. Subsequently, SDPR depletion induces epithelial-mesenchymal transition (EMT)-like phenotype. Finally, knockdown of SDPR activates transforming growth factor-ß (TGF-ß) signaling by upregulation of TGF-ß1 expression. In conclusion, our results showed that SDPR inhibits breast cancer progression by blocking TGF-ß signaling. Serum deprivation response suppresses cell proliferation and invasion in breast cancer cells. SDPR depletion induces epithelial-mesenchymal transition by activation of TGF-ß signaling.