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      Interferon-induced transmembrane protein 2 is a prognostic marker in colorectal cancer and promotes its progression by activating the PI3K/AKT pathway

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          Abstract

          Background

          Interferon-induced transmembrane protein 2 (IFITM2) is involved in repressing viral infection. This study aim to investigate the expression of IFITM2 in colorectal cancer (CRC) and explore its effect on cell proliferation, migration, and invasion.

          Methods

          We analyzed The Cancer Genome Atlas (TCGA) database for IFITM2 expression in colorectal cancer and used western blots to detect IFITM2 protein in specimens and cell lines of colorectal cancers. To assess the association between IFITM2 and clinical features, both univariate and multivariate cox regression analysis were conducted. Kaplan–Meier plots were used in the TCGA database to assess IFITM2 gene expression's prognostic significance. Silencing IFITM2 in SW480 and HCT116 cells was achieved by transient transfection with siRNA. Proliferation of CRCs was examined using Cell Counting Kit-8. The effect of IFITM2 on the migration and invasion of CRC cells was studied using wound healing and transwell assays. Gene set enrichment analysis (GSEA) was used to examine IFITM2-associated pathways and Western blotting was used to confirm it.

          Results

          IFITM2 was over-expressed in the CRC tissues and cells, with high IFITM2 expression related to the tumor N, M, and pathologic stages. The presence of IFITM2 significantly impacted patient survival in CRC. The proliferation of SW480 and HCT116 cells was suppressed when IFITM2 was silenced, resulting in weakened migration and invasion of CRC cells. GSEA analysis showed that IFITM2 was positively related to the phosphoinositide 3-kinase (PI3K)/AKT pathway, and western blot results confirmed that IFITM2 activated it.

          Conclusions

          IFITM2 was over-expressed in CRC and modulated the PI3K/AKT pathway to promote CRC cells proliferation and metastasis.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12672-024-01040-x.

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          Most cited references33

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

            Zefang Tang, Chenwei Li, Boxi Kang … (2017)
            Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.
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              TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

              Taiwen Li, Jingyu Fan, Binbin Wang … (2017)
              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
                Yonggang Liu: sdyylyg666@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): 27 May 2024
                Publication date PMC-release: 27 May 2024
                Publication date Collection: December 2024
                Volume: 15
                Electronic Location Identifier: 191
                Affiliations
                Department of Oncology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), ( https://ror.org/00wwb2b69) No.1 Jiazi Road, Shunde District, Foshan, 528308 Guangdong People’s Republic of China
                Article
                Publisher ID: 1040
                DOI: 10.1007/s12672-024-01040-x
                PMC ID: 11130111
                PubMed ID: 38802621
                SO-VID: 8aae7f81-2a47-4487-9a8f-285610dd3143
                Copyright © © The Author(s) 2024
                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 : 6 July 2023
                Date accepted : 16 May 2024
                Funding
                Funded by: Guangdong Medical Science and Technology Research Fund Project
                Award ID: B2023239
                Award Recipient :
                Funded by: Southern Medical University Shunde Hospital Clinical Research Startup Program
                Award ID: SRSP2022008
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media, LLC 2024

                Keywords: interferon-induced transmembrane protein 2,colorectal cancer,pi3k/akt pathway,proliferation,metastasis
                Data availability:
                Keywords: interferon-induced transmembrane protein 2, colorectal cancer, pi3k/akt pathway, proliferation, metastasis

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