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      Identification of biomarkers related to CD8 + T cell infiltration with gene co-expression network in clear cell renal cell carcinoma

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          Abstract

          Clear cell renal cell carcinoma (ccRCC) is an extremely common kind of kidney cancer in adults. Immunotherapy and targeted therapy are particularly effective at treating ccRCC. In this study, weighted gene co-expression network analysis and a deconvolution algorithm that quantifies the cellular composition of immune cells were used to analyze ccRCC expression data from the Gene Expression Omnibus database, and identify modules related to CD8 + T cells. Ten hub genes ( LCK, CD2, CD3D, CD3G, IRF1, IFNG, CCR5, CD8A, CCL5, and CXCL9) were identified by co-expression network and protein-protein interactions network analysis. Datasets obtained from The Cancer Genome Atlas were analyzed and the data revealed that the hub genes were meaningfully up-regulated in tumor tissues and correlated with promotion of tumor progression. After Kaplan-Meier analysis and Oncomine meta-analysis, CCL5 was selected as a prognostic biomarker. Finally, the experimental results show that reduced expression of CCL5 decreased cell proliferation and invasion in the ccRCC cell line. Various analyses were performed and verified, CCL5 is a potential biomarker and therapeutic target which related to CD8 + T cell infiltration in ccRCC.

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          Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma

          Lynda Vuong, Ritesh R. Kotecha, Martin Voss … (2019)
          Renal cell carcinoma stands out as one of the most immune infiltrated tumors in pan-cancer comparisons. Features of the tumor microenvironment heavily impact disease biology and may affect responses to systemic therapy. With evolving frontline options in the metastatic setting, several immune checkpoint blockade regimens have emerged as efficacious, and there is growing interest in characterizing features of tumor biology that can reproducibly prognosticate patients and/or predict the likelihood of deriving therapeutic benefit. Herein, we review pertinent characteristics of the tumor microenvironment with dedicated attention to candidate prognostic and predictive signatures as well as possible targets for future drug development.
          Article 0 comments Cited 206 times – based on 0 reviews     Review now
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            Immune infiltration in renal cell carcinoma

            Shichao Zhang, Erdong Zhang, Jinhua Long … (2019)
            Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumor‐infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS). We found that CD8+ T cells were associated with prolonged OS (hazard ratio [HR] = 0.09, 95% confidence interval [CI].01‐.53; P = 0.03) in chromophobe carcinoma (KICH). A higher proportion of regulatory T cells was associated with a worse outcome (HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma (KIRC). In renal papillary cell carcinoma (KIRP), M1 macrophages were associated with a favorable outcome (HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome (HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA4 and LAG3 were associated with a poor prognosis in KIRC, and IDO1 and PD‐L2 were associated with a poor prognosis in KIRP. This study indicates TIICs are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.
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              The FERM domain: organizing the structure and function of FAK.

              Margaret Frame, Hitesh Patel, Bryan Serrels … (2010)
              Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain. Recent structural work reveals that regulatory protein partners convert auto-inhibited FAK into its active state by binding to its FERM domain. Further, the identity of FAK FERM domain-interacting proteins yields clues as to how FAK coordinates diverse cellular responses, including cell adhesion, polarization, migration, survival and death, and suggests that FERM domains might mediate information transfer between the cell cortex and nucleus. Importantly, the FAK FERM domain might act as a paradigm for the actions of other FERM domain-containing proteins.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging (Albany NY)
                Journal ID (iso-abbrev): Aging (Albany NY)
                Journal ID (publisher-id): Aging
                Title: Aging (Albany NY)
                Publisher: Impact Journals
                ISSN (Electronic): 1945-4589
                Publication date Collection: 29 February 2020
                Publication date (Electronic): 20 February 2020
                Volume: 12
                Issue: 4
                Pages: 3694-3712
                Affiliations
                [1 ]Department of Urology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China
                [2 ]Department of Reproductive Biology and Transgenic Animal, China Medical University, Shenyang 110001, Liaoning, China
                [3 ]Department of Pediatric Intensive Care Unit, The Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Yuyan Zhu; email: yyzhu@cmu.edu.cn
                Article
                Publisher ID: 102841 Publisher ID: 102841
                DOI: 10.18632/aging.102841
                PMC ID: 7066925
                PubMed ID: 32081834
                SO-VID: 9717ab6c-bc96-4470-bcc0-6ba121987e1d
                Copyright © Copyright © 2020 Lin et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 01 October 2019
                Date accepted : 04 February 2020
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: clear cell renal cell carcinoma (ccrcc),cibersort,weighted gene co-expression network analysis (wgcna),cd8+ t cells,ccl5
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: clear cell renal cell carcinoma (ccrcc), cibersort, weighted gene co-expression network analysis (wgcna), cd8+ t cells, ccl5

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