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      Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

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          Abstract

          The tumor microenvironment (TME) is a complex system that plays an important role in tumor development and progression, but the current knowledge about its effect on bladder cancer (BC) is scarce. In this study, we performed a comprehensive analysis of the relationship between the TME and gene expression profiles to identify prognostic biomarkers for BC. The ESTIMATE algorithm was used to calculate immune and stromal scores of BC patients who were obtained from the Gene Expression Omnibus database. We found that the immune and stromal scores were associated with clinical characteristics and the prognosis of BC patients. Based on these scores, 104 immune-related differentially expressed genes were identified. Further, functional enrichment analysis revealed that these genes were mainly involved in the immune-related biological processes and signaling pathways. Three prognostic genes were then identified and used to establish a risk prediction model using Cox regression analyses. Kaplan–Meier survival analysis showed that the expression levels of COL1A1, COMP, and SERPINE2 significantly correlated with cancer-specific survival and overall survival of BC patients. Additionally, we validated the prognostic values of these genes using two independent cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases. Finally, the relationships between the three prognostic genes and several immune cells were evaluated using Tumor Immune Estimation Resource, indicating that the expression levels of COL1A1, COMP, and SERPINE2 correlated positively with the tumor infiltration levels of CD4 + T cells and macrophages. In conclusion, the current study comprehensively analyzed the TME and presented immune-related prognostic genes for BC, providing new insights into immunotherapeutic strategies for BC patients.

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          Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

          Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial–mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.
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            Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review.

            Some studies report that tumour progression in patients with non-muscle-invasive bladder cancer (NMIBC) is associated with a poor prognosis. However, no systematic evidence is available. The aim of the study was to systematically review literature to determine the long-term cancer-specific survival in patients with high-risk NMIBC (T1G3, multifocal, highly recurrent, or carcinoma in situ) having tumour progression. A systematic review was conducted by searching PubMed and the Cochrane library for studies published between 2006 and 2011. Additional studies were identified by scanning reference lists of relevant papers. We attempted to retrieve missing data by contacting the corresponding author. Keywords used included bladder cancer, high-risk, high grade, carcinoma in situ, non-muscle invasive bladder cancer, progression, and survival. Studies were included when they met the following criteria: inclusion of at least 75 patients having high-risk NMIBC, patients were initially treated conservatively with transurethral resection of the bladder tumour and intravesical instillations, a median follow-up of at least 48 mo, and reporting data on progression to muscle-invasive bladder cancer (MIBC) and death resulting from bladder cancer (BCa). Literature was systematically reviewed, and 19 trials were included, producing a total of 3088 patients, of which 659 (21%) showed progression to MIBC and 428 (14%) died as a result of BCa after a median follow-up of 48-123 mo. Survival after progression from high-risk NMIBC to MIBC was 35%. Progression to MIBC and BCa-related death in high-risk NMIBC were found to be relatively early events, occurring mainly within 48 mo. Finally, even in cases of early cystectomy in patients with high-risk NMIBC, a relevant proportion of these patients appear not be cured of their disease. This study provides systematically gathered evidence showing a poor prognosis for patients with high-risk NMIBC and tumour progression. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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              Collagen 1A1 (COL1A1) Is a Reliable Biomarker and Putative Therapeutic Target for Hepatocellular Carcinogenesis and Metastasis

              Increasing evidence shows that hepatocellular carcinoma (HCC) is a principal cause of cancer-related mortality globally, especially among Asian and African populations. Collagen type I α1 (COL1A1) is the major component of type I collagen. While aberrant expression of COL1A1 and COL1A2 is implicated in numerous cancers, the differential role of COL1A1 in malignant, premalignant and normal tissues remains unclear, and its clinical significance in HCC has not been elucidated. In this study, using bioinformatics analysis of publicly-available HCC microarray data from Gene Expression Omnibus (GEO) and RNAseq data from The Cancer Genome Atlas (TCGA) database, we determined that COL1A1 is significantly upregulated in HCC tumor tissues in comparison to normal tissues. Our analysis also revealed that COL1A1 confers survival advantage and enhanced oncogenicity on HCC cells. Interestingly, the siRNA-mediated silencing of COL1A1 expression (siCOLIA1) suppressed HCC cells clonogenicity, motility, invasiveness and tumorsphere formation. Concomitantly, siCOL1A1 abrogated Slug-dependent epithelial-to-mesenchymal transition (EMT) and HCC stemness gene-signature, by attenuating expression of stemness markers SOX2, OCT4 and CD133. The present study provides some mechanistic insight into COL1A1 activity in HCC and highlights its putative role as an important diagnostic biomarker and potential therapeutic target in early development and metastasis of HCC.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                28 July 2020
                2020
                : 10
                : 1302
                Affiliations
                [1] 1Department of Urology, The First Hospital of Jilin University , Changchun, China
                [2] 2Key Laboratory of Pathobiology, Ministry of Education, Jilin University , Changchun, China
                Author notes

                Edited by: Ja Hyeon Ku, Seoul National University, South Korea

                Reviewed by: Guru Sonpavde, Dana–Farber Cancer Institute, United States; Xiangqian Guo, Henan University, China

                *Correspondence: Yishu Wang wangys@ 123456jlu.edu.cn

                This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2020.01302
                7399341
                32850407
                980c6a19-238d-44c7-a2c7-45331aa7bdcf
                Copyright © 2020 Li, Teng, Liu, Liu, Zhang, Xu, Wang and Zhou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 May 2020
                : 23 June 2020
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 47, Pages: 12, Words: 6807
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                bladder cancer,tumor microenvironment,prognosis,immune score,stromal score,overall survival,cancer-specific survival

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