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Background: Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers and has a poor prognosis. As a critical RNA modification, 5-methylcytosine (m5C) has been reported to regulate tumor progression, including PAAD progression. However, a comprehensive analysis of m5C regulators in PAAD is lacking. Methods: In the present study, PAAD datasets were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and ArrayExpress databases. The expression pattern of m5C regulators were analyzed and patients were divided into different m5C clusters according to consensus clustering based on m5C regulators. Additionally, m5C differentially expressed genes (DEGs) were determined using Limma package. Based on m5C DEGs, patients were divided into m5C gene clusters. Moreover, m5C gene signatures were derived from m5C DEGs and a quantitative indicator, the m5C score, was developed from the m5C gene signatures. Results: Our study showed that m5C regulators were differentially expressed in patients with PAAD. The m5C clusters and gene clusters based on m5C regulators and m5C DEGs were related to immune cell infiltration, immune-related genes and patient survival status, indicating that m5C modification play a central role in regulating PAAD development partly by modulating immune microenvironment. Additionally, a quantitative indicator, the m5C score, was also developed and was related to a series of immune-related indicators. Moreover, the m5C score precisely predicted the immunotherapy response and prognosis of patients with PAAD. Conclusion: In summary, we confirmed that m5C regulators regulate PAAD development by modulating the immune microenvironment. In addition, a quantitative indicator, the m5C score, was developed to predict immunotherapy response and prognosis and assisted in identifying PAAD patients suitable for tailored immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Background: Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers and has a poor prognosis. As a critical RNA modification, 5-methylcytosine (m 5 C) has been reported to regulate tumor progression, including PAAD progression. However, a comprehensive analysis of m 5 C regulators in PAAD is lacking., Methods: In the present study, PAAD datasets were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and ArrayExpress databases. The expression pattern of m 5 C regulators were analyzed and patients were divided into different m 5 C clusters according to consensus clustering based on m 5 C regulators. Additionally, m 5 C differentially expressed genes (DEGs) were determined using Limma package. Based on m 5 C DEGs, patients were divided into m 5 C gene clusters. Moreover, m 5 C gene signatures were derived from m 5 C DEGs and a quantitative indicator, the m 5 C score, was developed from the m 5 C gene signatures., Results: Our study showed that m 5 C regulators were differentially expressed in patients with PAAD. The m 5 C clusters and gene clusters based on m 5 C regulators and m 5 C DEGs were related to immune cell infiltration, immune-related genes and patient survival status, indicating that m 5 C modification play a central role in regulating PAAD development partly by modulating immune microenvironment. Additionally, a quantitative indicator, the m 5 C score, was also developed and was related to a series of immune-related indicators. Moreover, the m 5 C score precisely predicted the immunotherapy response and prognosis of patients with PAAD., Conclusion: In summary, we confirmed that m 5 C regulators regulate PAAD development by modulating the immune microenvironment. In addition, a quantitative indicator, the m 5 C score, was developed to predict immunotherapy response and prognosis and assisted in identifying PAAD patients suitable for tailored immunotherapy strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Guo, Ma, Song, Min, Zhao, Hua, Zhang, Yang, Shi, Zhu, Gan, Li, Li and Su.)

Objective: Epithelium-specific ETS protein 3 (Ese-3) is a member of the ETS family that is associated with tumor progression. However, there is little knowledge about Ese-3 in skin cancer. This study was conducted to explore the effects of Ese-3 on clinical prognosis in skin cancer and the functions of HaCaT cells., Materials and Methods: Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and three GSE datasets (GSE15605, GSE46517, and GSE114445). Comparison of data between groups was performed by Student's t-test and chi square test. Survival analysis was performed using log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Enrichment analysis was used to predict Ese-3 related functions. Cell proliferation assays, colony formation assays, and flow cytometry were used to assess cell proliferation, while Transwell assays analyzed cell migration and invasion., Results: Compared with normal tissues, the Ese-3 mRNA in cutaneous malignant melanoma (CMM) patients was downregulated ( P <0.0001). Ese-3 mRNA was associated with the T stage ( χ 2 =10.015, P =0.018), clinical stage ( χ 2 =4.122, P =0.042), and prognosis in CMM patients ( P =0.0219) and was an independent prognostic predictor in CMM (HR=1.878, P =0.048). Enrichment analysis showed that differentially expressed proteins were associated with "protein kinase B (AKT) binding.", Conclusion: Ese-3 inhibited the proliferation, migration, and invasion of HaCaT cells by downregulating PSIP1 and NUCKS1 expression levels to inactivate the phosphorylation of AKT., (© 2021 by the Association of Clinical Scientists, Inc.)

Epithelium-specific Ets protein 3 (Ese-3), a member of the Ets family of transcription factors, plays an important role in the development of cancers. However, little is known concerning its role in colon cancer (CC). In this study, we demonstrate that the expression of Ese-3 is upregulated in CC tissues and elevated Ese-3 expression is relationship with advanced T stage ( P =0.037) and poor disease-free survival (DFS, P =0.044). Univariate and multivariate cox regression analyses show that Ese-3 expression may be an independent prognostic value for CC patients. Moreover, Ese-3 knockdown suppresses CC cell proliferation in vitro and in vivo, while Ese-3 overexpression has the opposite result. Further, we first demonstrate that EHD2 and INPP4B are the downstream genes of Ese-3. Subsequent investigation find that EHD2 is downregulated in CC tissues and knockdown of EHD2 significantly increase CC cell proliferation in vitro and vivo. Our findings reveal that Ese-3 promotes CC cell proliferation by downregulating EHD2 and transactivating INPP4B, and targeting the pathway may be a promising therapeutic target for CC patients., Competing Interests: None., (AJCR Copyright © 2021.)