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The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma

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收录情况： ◇ SCIE

作者：
Wu Wantao[1,2] * ; Li He[1,3] * ; Wang Zeyu[4,5] ; Dai Ziyu[4,5] ; Liang Xisong[4,5] ; Luo Peng[6] ; Liu Kun[7] ; Zhang Hao[8] ; Zhang Nan[9,10] ; Li Shuyu[11,*1] ; Zhang Chi[4,5,*2] ;
单位： [1]The Animal Laboratory Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. [2]Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. [3]Changsha Medical University, Changsha, China. [4]Department of Neurosurgery, Xiangya Hospital, Central South University Changsha, China. [5]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. [6]Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. [7]Department of Neurosugery, The Second People's Hospital of Hunan Province, The Hospital of Hunan University of Chinese Medicine, Changsha, China. [8]Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. [9]College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. [10]College of Bioinformatics Science and Technology, Harbin Medical University Harbin, China. [11]Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
出处：
DOI： 10.1016/j.heliyon.2023.e23915

关键词： Tertiary lymphoid structure Immunotherapy Machine learning Pan-cancer Genomic alteration

摘要：
Tertiary lymphoid structure (TLS) is a unique organ that carries out tumor cell elimination at tumor sites. It is continuously stimulated by inflammatory tumor signals and has been found to augment immunotherapy response. However, the detailed mechanisms behind it still need to be defined.To explore and grasp the whole picture of TLS from a pan-cancer view, we collected nine TLS-related genes from previous studies. We performed a comprehensive analysis of 9637 samples across 33 tumor types accessed from The Cancer Genome Atlas (TCGA) database. EdU, Transwell, and flow cytometry were performed on the feature gene PTGDS in U251 cells. The regulatory role of PTGDS on PD-L1 expression and macrophage polarization was verified.Alteration analysis showed that mutations of TLS-related genes were widespread and relatively high. Clustering analysis based on the expression of these nine genes obtained two distinct clusters, with high EIF1AY and PTGDS in cluster 2 and better overall survival in cluster 1. To distinguish the two clusters, we utilized six machine learning algorithms and filtrated EIF1AY, PTGDS, SKAP1, and RBP5 as the characteristic genes, among which the former two genes were proved to be hazardous. PTGDS was found to regulate PD-L1 expression and also promoted the proliferation and migration of U251 cells. The knockdown of PTGDS could reduce the migration of macrophages and inhibit the polarization of macrophages into M2-phenotype. In addition, we established a TLS score to demonstrate patients' TLS activity. The low TLS-score group overlapped with cluster 1 and displayed a better prognosis. Besides, the low TLS-score group was related to better immunotherapy responses. The HE staining of histopathological sections confirmed that the low TLS-score group exhibited higher infiltration of immune cells.This study reveals broad molecular, tumorigenic, and immunogenic signatures for further functional and therapeutic studies of tertiary lymphoid structure. The TLS score we established effectively predicted immunotherapy response and patients' survival. Its future application and combination await more research.© 2023 The Authors.

基金：
The authors acknowledge the financial support from the National Natural Science Foundation of China (NO. 82303035); Hunan Provincial Natural Science Foundation of China (NO. 2021JJ40321); The Science and Technology Innovation Program of Hunan Province (NO. 2020RC2065).
语种：
外文
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WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
最新[2025]版：
大类 | 4 区 综合性期刊
小类 | 4 区 综合性期刊
JCR分区：
出版当年[2022]版：
Q2 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]The Animal Laboratory Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. [2]Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
共同第一作者：
通讯作者：
通讯机构： [4]Department of Neurosurgery, Xiangya Hospital, Central South University Changsha, China. [5]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. [11]Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. [*1]Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. [*2]Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
推荐引用方式(GB/T 7714)：
Wu Wantao,Li He,Wang Zeyu,et al.The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma[J].HELIYON.2024,10(1):e23915.doi:10.1016/j.heliyon.2023.e23915.
APA：
Wu Wantao,Li He,Wang Zeyu,Dai Ziyu,Liang Xisong...&Zhang Chi.(2024).The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma.HELIYON,10,(1)
MLA：
Wu Wantao,et al."The tertiary lymphoid structure-related signature identified PTGDS in regulating PD-L1 and promoting the proliferation and migration of glioblastoma".HELIYON 10..1(2024):e23915

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