BackgroundYes-associated protein (YAP), a key player of the Hippo pathway, has been identified to have more and more important roles in tumorigenesis and may be an important biomarker for cancer therapy. YAP is important for bladder cancer cell migration, metastasis, and drug resistance; however, its function in bladder cancer stem cells remains unknown.PurposeThe aim of this work was to examine the expression and role of YAP in bladder cancer stem cells.Materials and methods:We identified that the expression level of YAP was significantly enriched in bladder cancer stem cells compared to noncancer stem cell population. Moreover, the effect of YAP on stem cell self-renewal was examined in bladder cancer cells by siRNA silencing approach. In addition, we showed that YAP is required for aldehyde dehydrogenase activity in bladder cancer cells.ResultsRNAseq analysis and quantitative real-time PCR results showed that silencing of YAP inhibited the expression of ALDH1A1 gene.ConclusionCollectively, our findings for the first time elucidated that YAP serves as a cancer stem cell regulator in bladder cancer, which provided a promising therapy strategy for patients with bladder cancer.

To date, there have not been great breakthroughs in immunotherapy for HER2 positive breast cancer (HPBC). This study aimed to build a risk model that might contribute to predicting prognosis and discriminating the immune landscape in patients with HPBC. We analyzed the tumor immune profile of HPBC patients from the TCGA using the ESTIMATE algorithm. Thirty survival-related differentially expressed genes were selected according to the ImmuneScore and StromalScore. A prognostic risk model consisting of PTGDR, PNOC and CCL23 was established by LASSO analysis, and all patients were classified into the high- and low-risk score groups according to the risk scores. Subsequently, the risk model was proven to be efficient and reliable. Immune related pathways were the dominantly enriched category. ssGSEA showed stronger immune infiltration in the low-risk score group, including the infiltration of TILs, CD8 T cells, NK cells, DCs, and so on. Moreover, we found that the expression of immune checkpoint genes, including PD-L1, CTLA-4, TIGIT, TIM-3 and LAG-3, was significantly upregulated in the low-risk score group. All the results were validated with corresponding data from the GEO database. In summary, our investigation indicated that the risk model composed of PTGDR, PNOC and CCL23 has potential to predict prognosis and evaluate the tumor immune microenvironment in HPBC patients. More importantly, HPBC patients with a low-risk scores are likely to benefit from immune treatment.

BackgroundPancreatic adenocarcinoma (PAAD) is one of the leading causes of cancer death worldwide. Alterations in DNA repair-related genes (DRGs) are observed in a variety of cancers and have been shown to affect the development and treatment of cancers. The aim of this study was to develop a DRG-related signature for predicting prognosis and therapeutic response in PAAD.MethodsWe constructed a DRG signature using least absolute shrinkage and selection operator (LASSO) Cox regression analysis in the TCGA training set. GEO datasets were used as the validation set. A predictive nomogram was constructed based on multivariate Cox regression. Calibration curve and decision curve analysis (DCA) were applied to validate the performance of the nomogram. The CIBERSORT and ssGSEA algorithms were utilized to explore the relationship between the prognostic signature and immune cell infiltration. The pRRophetic algorithm was used to estimate sensitivity to chemotherapeutic agents. The CellMiner database and PAAD cell lines were used to investigate the relationship between DRG expression and therapeutic response.ResultsWe developed a DRG signature consisting of three DRGs (RECQL, POLQ, and RAD17) that can predict prognosis in PAAD patients. A prognostic nomogram combining the risk score and clinical factors was developed for prognostic prediction. The DCA curve and the calibration curve demonstrated that the nomogram has a higher net benefit than the risk score and TNM staging system. Immune infiltration analysis demonstrated that the risk score was positively correlated with the proportions of activated NK cells and monocytes. Drug sensitivity analysis indicated that the signature has potential predictive value for chemotherapy. Analyses utilizing the CellMiner database showed that RAD17 expression is correlated with oxaliplatin. The dynamic changes in three DRGs in response to oxaliplatin were examined by RT-qPCR, and the results show that RAD17 is upregulated in response to oxaliplatin in PAAD cell lines.ConclusionWe constructed and validated a novel DRG signature for prediction of the prognosis and drug sensitivity of patients with PAAD. Our study provides a theoretical basis for further unraveling the molecular pathogenesis of PAAD and helps clinicians tailor systemic therapies within the framework of individualized treatment.