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      BLCA prognostic model creation and validation based on immune gene-metabolic gene combination

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          Abstract

          Background

          Bladder cancer (BLCA) is a prevalent urinary system malignancy. Understanding the interplay of immunological and metabolic genes in BLCA is crucial for prognosis and treatment.

          Methods

          Immune/metabolism genes were extracted, their expression profiles analyzed. NMF clustering found prognostic genes. Immunocyte infiltration and tumor microenvironment were examined. Risk prognostic signature using Cox/LASSO methods was developed. Immunological Microenvironment and functional enrichment analysis explored. Immunotherapy response and somatic mutations evaluated. RT-qPCR validated gene expression.

          Results

          We investigated these genes in 614 BLCA samples, identifying relevant prognostic genes. We developed a predictive feature and signature comprising 7 genes (POLE2, AHNAK, SHMT2, NR2F1, TFRC, OAS1, CHKB). This immune and metabolism-related gene (IMRG) signature showed superior predictive performance across multiple datasets and was independent of clinical indicators. Immunotherapy response and immune cell infiltration correlated with the risk score. Functional enrichment analysis revealed distinct biological pathways between low- and high-risk groups. The signature demonstrated higher prediction accuracy than other signatures. qRT-PCR confirmed differential gene expression and immunotherapy response.

          Conclusions

          The model in our work is a novel assessment tool to measure immunotherapy’s effectiveness and anticipate BLCA patients’ prognosis, offering new avenues for immunological biomarkers and targeted treatments.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12672-023-00853-6.

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          Most cited references83

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          Cancer statistics in China and United States, 2022: profiles, trends, and determinants

          Changfa Xia, Xuesi Dong, He. Li … (2022)
          Background: The cancer burden in the United States of America (USA) has decreased gradually. However, China is experiencing a transition in its cancer profiles, with greater incidence of cancers that were previously more common in the USA. This study compared the latest cancer profiles, trends, and determinants between China and USA. Methods: This was a comparative study using open-source data. Cancer cases and deaths in 2022 were calculated using cancer estimates from GLOBOCAN 2020 and population estimates from the United Nations. Trends in cancer incidence and mortality rates in the USA used data from the Surveillance, Epidemiology, and End Results program and National Center for Health Statistics. Chinese data were obtained from cancer registry reports. Data from the Global Burden of Disease 2019 and a decomposition method were used to express cancer deaths as the product of four determinant factors. Results: In 2022, there will be approximately 4,820,000 and 2,370,000 new cancer cases, and 3,210,000 and 640,000 cancer deaths in China and the USA, respectively. The most common cancers are lung cancer in China and breast cancer in the USA, and lung cancer is the leading cause of cancer death in both. Age-standardized incidence and mortality rates for lung cancer and colorectal cancer in the USA have decreased significantly recently, but rates of liver cancer have increased slightly. Rates of stomach, liver, and esophageal cancer decreased gradually in China, but rates have increased for colorectal cancer in the whole population, prostate cancer in men, and other seven cancer types in women. Increases in adult population size and population aging were major determinants for incremental cancer deaths, and case-fatality rates contributed to reduced cancer deaths in both countries. Conclusions: The decreasing cancer burden in liver, stomach, and esophagus, and increasing burden in lung, colorectum, breast, and prostate, mean that cancer profiles in China and the USA are converging. Population aging is a growing determinant of incremental cancer burden. Progress in cancer prevention and care in the USA, and measures to actively respond to population aging, may help China to reduce the cancer burden.
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            European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines

            J Witjes, Harman Max Bruins, Richard Cathomas … (2020)
            This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).
            Article 0 comments Cited 593 times – based on 0 reviews     Review now
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              Intratumoral CD4 + T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer

              David Oh, Serena S. Kwek, Siddharth S. Raju … (2020)
              Summary Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
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                Author and article information

                Contributors
                Chun Li: lichun2023@Hotmail.com
                Yu Guan: guanyu928@126.com
                He-Xi Du: duhexi1989@163.com
                Journal
                Journal ID (nlm-ta): Discov Oncol
                Journal ID (iso-abbrev): Discov Oncol
                Title: Discover. Oncology
                Publisher: Springer US (New York )
                ISSN (Electronic): 2730-6011
                Publication date (Electronic): 16 December 2023
                Publication date PMC-release: 16 December 2023
                Publication date Collection: December 2023
                Volume: 14
                Electronic Location Identifier: 232
                Affiliations
                [1 ]GRID grid.412679.f, ISNI 0000 0004 1771 3402, Department of Urology, , the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, ; No. 218 Jixi Road, Hefei, 230022 Anhui People’s Republic of China
                [2 ]Institute of Urology, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, Anhui People’s Republic of China
                [3 ]Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, ( https://ror.org/03xb04968) Hefei, Anhui People’s Republic of China
                Article
                Publisher ID: 853
                DOI: 10.1007/s12672-023-00853-6
                PMC ID: 10725402
                PubMed ID: 38103068
                SO-VID: 0779eee4-f4a1-4a8a-8edb-a2f4d54aea7b
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 12 September 2023
                Date accepted : 14 December 2023
                Funding
                Funded by: National Natural Science Fund of China
                Award ID: 82100815
                Award Recipient :
                Funded by: Anhui Natural Science Foundation
                Award ID: 2108085QH315
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media, LLC 2023

                Keywords: bladder cancer,prognostic model,immunogene,integrated biomarker approach,prognosis
                Data availability:
                Keywords: bladder cancer, prognostic model, immunogene, integrated biomarker approach, prognosis

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