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      FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma

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          Abstract

          Background

          As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people’s health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.

          Methods

          This study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package “limma” or “DESeq2” in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.

          Results

          The FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.

          Conclusions

          The increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.

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          Most cited references44

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

          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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            Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

            In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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              Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

              Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1970493Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1209372Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role:
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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                22 November 2023
                2023
                : 14
                : 1295831
                Affiliations
                [1] 1 Department of Dermatology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [2] 2 Department of Dermatology, Changhai Hospital, Naval Medical University , Shanghai, China
                [3] 3 Department of Dermatology, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [4] 4 Department of Neurology, Minhang Hospital, Fudan University/Central Hospital of Minhang District , Shanghai, China
                [5] 5 Department of General Surgery, Zhongshan Hospital, Fudan University , Shanghai, China
                [6] 6 Department of Dermatology, Huashan Hospital, Fudan University , Shanghai, China
                Author notes

                Edited by: Hongbao Yang, China Pharmaceutical University, China

                Reviewed by: Da Sun, Wenzhou University, China; Qiang Li, Ludwig Maximilian University of Munich, Germany; Fang Yang, Charité University Medicine Berlin, Germany

                *Correspondence: Wuqing Wang, wangwuqing121@ 123456sina.com ; Xinling Bi, bixinling@ 123456163.com

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2023.1295831
                10703153
                38077326
                989927ec-ccbb-4f84-be9e-1b58db68cefe
                Copyright © 2023 Cai, Duan, Li, Liu, Gong, Hong, He, Xuanyuan, Chen, Bi and Wang

                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
                : 17 September 2023
                : 07 November 2023
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 44, Pages: 14, Words: 4882
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The whole program obtained sponsorship from National Natural Science Foundation of the People’s Republic of China (82004366), Natural Science Foundation of Shanghai (YKHHFX01190408), Training Program for High-caliber Talents of Clinical Research at Affiliated Hospitals of SHUTCM (NO. 2023LCRC09), Shanghai Municipal Commission of science and technology, Sailing Program (NO. 22YF1449500), and Special Clinical Research Special Project of Shanghai Municipal Health Commission (20234Y0163).
                Categories
                Immunology
                Original Research
                Custom metadata
                Molecular Innate Immunity

                Immunology
                fanci,skin cutaneous melanoma,prognostic biomarker,immune infiltrates,immunotherapy
                Immunology
                fanci, skin cutaneous melanoma, prognostic biomarker, immune infiltrates, immunotherapy

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