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      Comprehensive Analysis of Immune Implications and Prognostic Value of SPI1 in Gastric Cancer

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          Abstract

          Background

          The transcription factor Spi-1 proto-oncogene (SPI1, also known as PU.1) is a key regulator of signal communication in the immune system and is essential for the development of myeloid cells and lymphocytes. However, the potential role of SPI1 in gastric cancer (GC) and the correlations between SPI1 and immune infiltration remain unclear.

          Methods

          In the present study, multiple databases including ONCOMINE, TIMER, Kaplan–Meier Plotter, and The Cancer Genome Atlas were used to explore the expression levels and prognostic value of SPI1 in GC. cBioPortal was used to explore the possible reasons for the increased expression of SPI1 in GC. The correlations between SPI1 expression and tumor-infiltrating immune cells (TICs) were analyzed using CIBERSORT and TIMER. Gene set enrichment analysis was used to determine the biological function of SPI1 in the development of GC. In addition, a risk signature based on SPI1-related immunomodulators was constructed to accurately evaluate the prognosis of patients with GC. The upregulation of SPI1 expression in GC was further confirmed through immunohistochemistry, western blotting, and real-time quantitative PCR (RT-qPCR) assay.

          Results

          The expression of SPI1 was increased significantly in GC according to multiple databases, and high expression of SPI1 was related to poor prognosis and progression of GC. The main factor influencing the high expression of SPI1 mRNA in GC may be diploidy, not DNA methylation. Moreover, immunohistochemistry, western blotting, and RT-qPCR assays also confirmed the upregulated expression of SPI1 in GC. CIBERSORT analysis revealed that SPI1 expression was correlated with seven types of TICs (naive B cells, resting memory CD4 T cells, activated memory CD4 T cells, activated natural killer cells, resting natural killer cells, M2 macrophages, and resting dendritic cells). Gene set enrichment analysis indicated that SPI1 might be related to immune activation in GC and participate in cell cycle regulation. In addition, based on SPI1-related immunomodulators, we developed multiple-gene risk prediction signatures and constructed a nomogram that can independently predict the clinical outcome of GC.

          Conclusion

          The results of the present study suggest that SPI1 has a critical role in determining the prognosis of GC patients and may be a potential immunotherapeutic target.

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          Most cited references45

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          Cancer statistics, 2019

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, 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, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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            The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

            The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. © 2012 AACR.
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              TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

              Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.
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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
                14 February 2022
                2022
                : 12
                : 820568
                Affiliations
                [1] 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University , Nanchang, China
                [2] 2Department of Emergency Surgery, The First Affiliated Hospital of Nanchang University , Nanchang, China
                Author notes

                Edited by: Dakang Xu, Shanghai Jiao Tong University, China

                Reviewed by: Taicheng Zhou, The Sixth Affiliated Hospital of Sun Yat-sen University, China; Xiaolong Liang, First Affiliated Hospital of Chongqing Medical University, China

                *Correspondence: Mengmeng Jiang, jiangmmaz@ 123456126.com ; Zhigang Jie, jiezg123@ 123456126.com

                This article was submitted to Gastrointestinal Cancers: Gastric & Esophageal Cancers, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work

                Article
                10.3389/fonc.2022.820568
                8882873
                35237521
                309f7a61-94be-48ed-8e5d-e86732b6ffc9
                Copyright © 2022 Huang, Chen, Jie and Jiang

                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
                : 14 December 2021
                : 19 January 2022
                Page count
                Figures: 9, Tables: 1, Equations: 0, References: 45, Pages: 14, Words: 6201
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                gastric cancer,spi1,prognostic markers,risk signature,nomogram
                Oncology & Radiotherapy
                gastric cancer, spi1, prognostic markers, risk signature, nomogram

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