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Abstract Background The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor overall prognosis. However, curative resection during the early stages of the disease can greatly improve survival rates, highlighting the importance of early screening and detection. Studies of noncoding RNAs, primarily microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), provide important insights into strategies for the early detection of KRAS-driven PDAC. Here, we summarize our studies and review current reports on research investigating KRAS-related miRNAs and lncRNAs, emphasizing their aberrant expression, mechanisms, carcinogenic effects, and prognostic and predictive capacities in PDAC. Keywords: Pancreatic ductal adenocarcinoma, KRAS, Noncoding RNAs, microRNAs, Long noncoding RNAs

Aberrantly expressed microRNA (miRNA) is frequently associated with a variety of cancers, including pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the expression and possible role of miR-217 in PDAC. Data obtained by locked nucleic acid in situ hybridization and real-time quantitative polymerase chain reaction showed that miR-217 was downregulated in 76.2% (16/21) of PDAC tissues and in all tested PDAC cell lines when compared with the corresponding normal pancreatic tissue. Overexpression of miR-217 in PDAC cells inhibited tumor cell growth and anchorage-independent colony formation and miR-217 decreased tumor cell growth in nude mouse xenografts in vivo. Using in silico predictions, KRAS was defined as a potential direct target of miR-217. Data from the dual-luciferase reporter gene assay showed that KRAS was a direct target of miR-217. Upregulation of miR-217 could decrease KRAS protein levels and reduce the constitutive phosphorylation of downstream AKT. Downregulation of miR-217 expression in PDAC cells could increase cell anchorage-independent colony formation and KRAS protein levels. Furthermore, miR-217 expression was observed to be negatively correlated with KRAS protein expression in PDAC cell lines. We conclude that the frequently downregulated miR-217 can regulate KRAS and function as a tumor suppressor in PDAC. Therefore, miR-217 may serve as a useful therapeutic agent for miRNA-based PDAC therapy. [ABSTRACT FROM PUBLISHER]