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Background. Many studies have found that chromatin regulators (CRs) are correlated with tumorigenesis and disease prognosis. Here, we attempted to build a new CR-related gene model to predict breast cancer (BC) survival status. Methods. First, the CR-related differentially expressed genes (DEGs) were screened in normal and tumor breast tissues, and the potential mechanism of CR-related DEGs was determined by function analysis. Based on the prognostic DEGs, the Cox regression model was applied to build a signature for BC. Then, survival and receiver operating characteristic (ROC) curves were performed to validate the signature’s efficacy and identify its independent prognostic value. The CIBERSORT and tumor immune dysfunction and exclusion (TIDE) algorithms were used to assess the immune cells infiltration and immunotherapy efficacy for this signature, respectively. Additionally, a novel nomogram was also built for clinical decisions. Results. We identified 98 CR-related DEGs in breast tissues and constructed a novel 6 CR-related gene signature (ARID5A, ASCL1, IKZF3, KDM4B, PRDM11, and TFF1) to predict the outcome of BC patients. The prognostic value of this CR-related gene signature was validated with outstanding predictive performance. The TIDE analysis revealed that the high-risk group patients had a better response to immune checkpoint blockade (ICB) therapy. Conclusion. A new CR-related gene signature was built, and this signature could provide the independent predictive capability of prognosis and immunotherapy efficacy for BC patients.

SLC1A5 has been demonstrated to be associated with the progression of other tumors; however, studies are lacking in hepatocellular carcinoma (HCC). Here, we identify SLC1A5, as a novel ferroptosis factor, for HCC patients.The core biomarkers were identified by univariate and multivariate Cox regression analysis, and the genes present in liver cancer were validated using the public database. Then, gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms. In addition, we explore the relationship between SLC1A5 and clinical factors. Finally, we determine the effect of SLC1A5 on HCC cells using real-time PCR, cell scratch analysis, transwell analysis, and CCK8 analysis in molecular biology experiments.Cox regression model shows that SLC1A5 was an independent risk factor for HCC patients. GSEA results indicated high expression of SLC1A5 related to the fatty acid metabolism pathway. Clinical correlation analysis demonstrates that alpha-fetoprotein (AFP) expression was positively correlated with SLC1A5 (p = 8e-05), and the higher tumor stage means the higher expression of SLC1A5 (p = .02). In addition, SLC1A5 expression was also positively correlated with vascular infiltration of HCC (p = .04). Furthermore, the SLC1A5 function deficiency experiment explored its underlying impact on the biological function of HCC. qPCR, also called quantitative polymerase chain reaction, confirmed that SLC1A5 was highly expressed in liver cancer when compared with normal tissues. Studies have also shown that downregulation of SLC1A5 can inhibit wound healing, invasion, and proliferation of HCC cells.In conclusion, ferroptosis factor SLC1A5 is a new therapeutic target for hepatocellular carcinoma.

Gallbladder cancer (GBC) is commonly regarded as one of the most lethal malignant tumor types with poor prognosis. Kinesin family member 15 (KIF15) is reported to be tightly related with progression of multiple cancer types which, however, has not been clarified in GBC so far. KIF15 was significantly up-regulated in clinical GBC tissues compared with that in para-carcinoma tissues and the expression level was also correlated with tumor malignancies. In addition to tissues, GBC cells also exhibited a high expression abundance of KIF15. After down-regulating KIF15 via lentiviral transfection, GBC cell proliferation and migration were both inhibited, while cell apoptosis was promoted markedly. Likewise, silencing KIF15 significantly interfered the growth of nude mouse xenografts. Our experiments in GBC cell lines also demonstrated that KIF15 overexpression accelerated cell proliferation but lessened cell apoptosis in both GBC-SD and SGC-996 cells. Further investigation of the mechanism occurring in GBC inhibition mediated by KIF15 knockdown revealed that KIF15 deficiency led to decreased activity of several signaling pathways (TNF, PI3K/AKT and MAPK), a reduction of CDK6 expression regulated by enhanced p21, and HSP60 absence. Following the treatment of shCtrl- and shKIF15-transfected cells with AKT activator, we found that anti-tumor effects resulting from KIF15 deficiency could be relieved by AKT activator in both experimental cells. Overall, for the first time, we demonstrated that KIF15 was overexpressed in GBC and displayed a close relationship between KIF15 levels and GBC clinical stages. Furthermore, low expression of KIF15 resulted in obvious anti-tumor effects.