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      A novel prognostic model based on cellular senescence-related gene signature for bladder cancer

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          Abstract

          Background

          Cellular senescence plays crucial role in the progression of tumors. However, the expression patterns and clinical significance of cellular senescence-related genes in bladder cancer (BCa) are still not clearly clarified. This study aimed to establish a prognosis model based on senescence-related genes in BCa.

          Methods

          The transcriptional profile data and clinical information of BCa were downloaded from TCGA and GEO databases. The least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analyses were performed to develop a prognostic model in the TCGA cohort. The GSE13507 cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate underlying mechanisms.

          Results

          A six-gene signature (CBX7, EPHA3, STK40, TGFB1I1, SREBF1, MYC) was constructed in the TCGA databases. Patients were classified into high risk and low risk group in terms of the median risk score. Survival analysis revealed that patients in the higher risk group presented significantly worse prognosis. Receiver operating characteristic (ROC) curve analysis verified the moderate predictive power of the risk model based on the six senescence-related genes signature. Further analysis indicated that the clinicopathological features analysis were significantly different between the two risk groups. As expected, the signature presented prognostic significance in the GSE13507 cohort. Functional analysis indicated that immune-related pathways activity, immune cell infiltration and immune-related function were different between two risk groups. In addition, risk score were positively correlated with multiple immunotherapy biomarkers.

          Conclusion

          Our study revealed that a novel model based on senescence-related genes could serve as a reliable predictor of survival for patients with BCa.

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          Most cited references74

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          Cancer Statistics, 2021

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            Inflammation and Cancer: Triggers, Mechanisms, and Consequences

            Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression and metastasis. We discuss how tumor promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis or tissue repair, and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatio-temporal considerations. Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for the further development of anti-cancer therapies. Grivennikov and Greten review the mechanisms underlying the initiation of pro-tumorigenic inflammatory responses, how these evolve throughout the different stages of tumor development and the plasticity of the cells within the tumor microenvironment.
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              Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

              New England Journal of Medicine, 376(11), 1015-1026
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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
                23 November 2022
                2022
                : 12
                : 937951
                Affiliations
                [1] 1 Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang , Jiangxi, China
                [2] 2 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang , Jiangxi, China
                Author notes

                Edited by: Yair Lotan, University of Texas Southwestern Medical Center, United States

                Reviewed by: Timothy Clinton, Harvard Medical School, United States; Shengjie Chai, Uber Technologies, Inc., United States

                *Correspondence: Wenjie Xie, xwjurol@ 123456sina.com

                †These authors have contributed equally to this work

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

                Article
                10.3389/fonc.2022.937951
                9727082
                36505846
                5ff1691f-2c9b-44f5-aee6-daf971bb091d
                Copyright © 2022 Luo, Li, Gong, Xi and Xie

                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 2022
                : 31 October 2022
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 74, Pages: 15, Words: 5201
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                cellular senescence,bladder cancer,prognosis signature,immune infiltration,biomarkers

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