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      DPP6 and MFAP5 are associated with immune infiltration as diagnostic biomarkers in distinguishing uterine leiomyosarcoma from leiomyoma

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          Abstract

          Objective

          Uterine leiomyosarcoma (ULMS) is the most common subtype of uterine sarcoma and is difficult to discern from uterine leiomyoma (ULM) preoperatively. The aim of the study was to determine the potential and significance of immune -related diagnostic biomarkers in distinguishing ULMS from ULM.

          Methods

          Two public gene expression profiles (GSE36610 and GSE64763) from the GEO datasets containing ULMS and ULM samples were downloaded. Differentially expressed genes (DEGs) were selected and determined among 37 ULMS and 25 ULM control samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Disease Ontology (DO) enrichment analyses as well as gene set enrichment analysis (GSEA). The candidate biomarkers were identified by least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the biomarker expression levels and diagnostic value in ULMS were verified in the GSE9511 and GSE68295 datasets (12 ULMS and 10 ULM), and validated by immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in ULMS.

          Result

          In total, 55 DEGs were recognized via GO analysis, and KEGG analyses revealed that the DEGs were enriched in nuclear division, and cell cycle. The recognized DEGs were primarily implicated in non−small cell lung carcinoma and breast carcinoma. Gene sets related to the cell cycle and DNA replication were activated in ULMS. DPP6 and MFAP5 were distinguished as diagnostic biomarkers of ULMS (AUC = 0.957, AUC = 0.899, respectively), and they were verified in the GSE9511 and GSE68295 datasets (AUC = 0.983, AUC = 0.942, respectively). The low expression of DPP6 and MFAP5 were associated with ULMS. In addition, the analysis of the immune microenvironment indicated that resting mast cells were positively correlated with DPP6 and MFAP5 expression and that eosinophils and M0 macrophages were negatively correlated with DPP6 expression (P<0.05).

          Conclusion

          These findings indicated that DPP6 and MFAP5 are diagnostic biomarkers of ULMS, thereby offering a novel perspective for future studies on the occurrence, function and molecular mechanisms of ULMS.

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          Most cited references41

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          Robust enumeration of cell subsets from tissue expression profiles

          We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).
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            Proteomics. Tissue-based map of the human proteome.

            Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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              The sva package for removing batch effects and other unwanted variation in high-throughput experiments.

              Heterogeneity and latent variables are now widely recognized as major sources of bias and variability in high-throughput experiments. The most well-known source of latent variation in genomic experiments are batch effects-when samples are processed on different days, in different groups or by different people. However, there are also a large number of other variables that may have a major impact on high-throughput measurements. Here we describe the sva package for identifying, estimating and removing unwanted sources of variation in high-throughput experiments. The sva package supports surrogate variable estimation with the sva function, direct adjustment for known batch effects with the ComBat function and adjustment for batch and latent variables in prediction problems with the fsva function.
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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
                30 November 2022
                2022
                : 12
                : 1084192
                Affiliations
                [1] 1 Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou , Fujian, China
                [2] 2 Department of Clinical Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou , Fujian, China
                [3] 3 Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou , Fujian, China
                [4] 4 Department of Gynecology, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou , Fujian, China
                Author notes

                Edited by: Nan Zhang, Harbin Medical University, China

                Reviewed by: Pan Li, Southern Medical University, China; Xia Chen, Southern Medical University, China

                *Correspondence: Zhuna Wu, wuzhuna@ 123456aliyun.com

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.1084192
                9748670
                36531033
                9c6aae5c-97dc-43a5-8657-4ea5573a764e
                Copyright © 2022 Ke, You, Xu, Wu, Lin and Wu

                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
                : 30 October 2022
                : 16 November 2022
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 41, Pages: 11, Words: 3717
                Funding
                Funded by: Fujian Provincial Health Technology Project , doi 10.13039/501100017686;
                Award ID: 2019-1-15
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                diagnostic biomarkers,machine-learning,dpp6,mfap5,immune infiltration,uterine leiomyosarcoma

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