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      Identification of genes of prognostic value in the ccRCC microenvironment from TCGA database

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          Abstract

          Background

          Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma. Bioinformatics analyses were used to screen candidate genes associated with the prognosis and microenvironment of ccRCC and elucidate the underlying molecular mechanisms of action.

          Methods

          The gene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database. The ESTIMATE algorithm was used to compute the immune and stromal scores of patients. Based on the median immune/stromal scores, all patients were sorted into low‐ and high‐immune/stromal score groups. Differentially expressed genes (DEGs) were extracted from high‐ versus low‐immune/stromal score groups and were described using functional annotations and protein‒protein interaction (PPI) network.

          Results

          Patients in the high‐immune/stromal score group had poorer survival outcome. In total, 95 DEGs (48 upregulated and 47 downregulated genes) were screened from the gene expression profiles of patients with high immune and stromal scores. The genes were primarily involved in six signaling pathways. Among the 95 DEGs, 43 were markedly related to overall survival of patients. The PPI network identified the top 10 hub genes— CD19, CD79A, IL10, IGLL5, POU2AF1, CCL19, AMBP, CCL18, CCL21, and IGJ—and four modules. Enrichment analyses revealed that the genes in the most important module were involved in the B‐cell receptor signaling pathway.

          Conclusion

          This study mainly revealed the relationship between the ccRCC microenvironment and prognosis of patients. These results also increase the understanding of how gene expression patterns can impact the prognosis and development of ccRCC by modulating the tumor microenvironment. The results could contribute to the search for ccRCC biomarkers and therapeutic targets.

          Abstract

          Identification of genes of prognostic value in the ccRCC microenvironment from TCGA database

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          Most cited references27

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          Cancer stemness, intratumoral heterogeneity, and immune response across cancers

          Regulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype (“stemness”) on the immunological properties of cancer has not been systematically explored. Using gene-expression–based metrics, we evaluated the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers. We found pervasive negative associations between cancer stemness and anticancer immunity. This occurred despite high stemness cancers exhibiting increased mutation load, cancer-testis antigen expression, and intratumoral heterogeneity. Stemness was also strongly associated with cell-intrinsic suppression of endogenous retroviruses and type I IFN signaling, and increased expression of multiple therapeutically accessible immunosuppressive pathways. Thus, stemness is not only a fundamental process in cancer progression but may provide a mechanistic link between antigenicity, intratumoral heterogeneity, and immune suppression across cancers.
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            Role of the Tumor Microenvironment in Breast Cancer

            In recent years, it has been shown that breast cancer consists not only of neoplastic cells, but also of significant alterations in the surrounding stroma or tumor microenvironment. These alterations are now recognized as a critical element for breast cancer development and progression, as well as potential therapeutic targets. Various components of the breast cancer microenvironment, such as suppressive immune cells, soluble factors and altered extracellular matrix, act together to impede effective antitumor immunity and promote breast cancer progression and metastasis. Stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, some of which are prognostic of clinical outcome. Several new therapies targeting stromal components are in development or undergoing clinical trials. We focus herein on the composition of the breast cancer microenvironment and concomitant molecular alterations, the specific interplay between various cell types and cancer cells, and the clinical implications of these findings.
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              The paradoxical role of IL-10 in immunity and cancer.

              Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated. In this review, we will discuss a wide variety of evidence of IL-10 in immunity and cancer in an effort to illuminate the remaining mysteries in the function of this cytokine that, when fully understood, may prove to be a powerful tool in the battle against cancer.
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                Author and article information

                Contributors
                lvcai815@163.com
                Journal
                Mol Genet Genomic Med
                Mol Genet Genomic Med
                10.1002/(ISSN)2324-9269
                MGG3
                Molecular Genetics & Genomic Medicine
                John Wiley and Sons Inc. (Hoboken )
                2324-9269
                03 February 2020
                April 2020
                : 8
                : 4 ( doiID: 10.1002/mgg3.v8.4 )
                : e1159
                Affiliations
                [ 1 ] Department of Urology Central South University Xiangya School of Medicine Affiliated Haikou Hospital Haikou Hainan China
                [ 2 ] Laboratory of Developmental Cell Biology and Disease School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical University Wenzhou Zhejiang China
                [ 3 ] Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital Haikou Hainan China
                Author notes
                [*] [* ] Correspondence

                Cai Lv, Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan 570208, China.

                Email: lvcai815@ 123456163.com

                Author information
                https://orcid.org/0000-0002-9557-4095
                Article
                MGG31159
                10.1002/mgg3.1159
                7196483
                0e3063fd-5093-4d3b-bfc7-175ee56b97e2
                © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 September 2019
                : 24 December 2019
                : 13 January 2020
                Page count
                Figures: 10, Tables: 4, Pages: 12, Words: 6578
                Funding
                Funded by: Natural Science Foundation of Hainan Province , open-funder-registry 10.13039/501100004761;
                Award ID: 819MS136
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.1 mode:remove_FC converted:03.05.2020

                ccrcc,immune scores,microenvironment,stromal scores,tcga database

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