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      KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma

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          Abstract

          Background

          The incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC.

          Methods

          The mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1.

          Results

          KNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes.

          Conclusion

          KNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC.

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          Most cited references68

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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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            limma powers differential expression analyses for RNA-sequencing and microarray studies

            limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.
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              Cancer Statistics, 2021

              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) 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 (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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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
                27 January 2023
                2023
                : 13
                : 1090779
                Affiliations
                [1] 1 Department of Rehabilitation, School of Nursing, Jilin University , Changchun, China
                [2] 2 The Department of Obstetrics and Gynecology, The Second Hospital of Jilin University , Changchun, Jilin, China
                [3] 3 Department of Rehabilitation, The Second Hospital of Jilin University , Changchun, Jilin, China
                Author notes

                Edited by: Andrzej Semczuk, Medical University of Lublin, Poland

                Reviewed by: Shuangdi Li, Shanghai First Maternity and Infant Hospital, China; Wu Ren, Huazhong University of Science and Technology, China

                *Correspondence: Lijing Zhao, zhao_lj@ 123456jlu.edu.cn ; Shuhua Zhao, zhaoshuhua-1966@ 123456163.com

                †These authors have contributed equally to this work

                This article was submitted to Gynecological Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2023.1090779
                9913269
                36776306
                b900a2bd-d24d-4b22-947e-264461378471
                Copyright © 2023 He, Li, Huang, Zhao, Wang, Wang, Chen, Wang, Yi, Zhao and Zhao

                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
                : 06 November 2022
                : 11 January 2023
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 68, Pages: 15, Words: 6900
                Funding
                This study was supported by a grant from the Jilin Provincial Department of Science and Technology project (grant number: 20210204200YY), the project of Jilin Province Development and Reform Commission (2014G073), the project of Jilin Province of Department Finance (2019SCZT050) and the project of Jilin Province of Department Finance (2019SCZT040).
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                knl1,uterine corpus endometrial carcinoma,bioinformatics,prognosis,biomarker

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