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

作者全名："Wu, Wantao; Li, He; Wang, Zeyu; Dai, Ziyu; Liang, Xisong; Luo, Peng; Liu, Kun; Zhang, Hao; Zhang, Nan; Li, Shuyu; Zhang, Chi"

作者地址："[Wu, Wantao; Li, He] Cent South Univ, Hunan Canc Hosp, Anim Lab Ctr, Changsha, Peoples R China; [Wu, Wantao; Li, He] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha, Peoples R China; [Wu, Wantao] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Peoples R China; [Li, He] Changsha Med Univ, Changsha, Peoples R China; [Dai, Ziyu; Liang, Xisong; Zhang, Chi] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China; [Wang, Zeyu; Dai, Ziyu; Liang, Xisong; Zhang, Chi] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China; [Luo, Peng] Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China; [Liu, Kun] Hosp Hunan Univ Chinese Med, Peoples Hosp Hunan Prov 2, Dept Neurosugery, Changsha, Peoples R China; [Zhang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Zhang, Nan] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan, Peoples R China; [Zhang, Nan] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China; [Li, Shuyu] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thyroid & Breast Surg, Wuhan, Peoples R China"

通信作者："Zhang, C (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China.; Zhang, C (通讯作者)，Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.; Li, SY (通讯作者)，Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Thyroid & Breast Surg, Wuhan, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001147348300001

JCR分区：Q2

影响因子：4

年份：2024

卷号：10

期号：1

开始页：　

结束页：　

文献类型：Article

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

摘要："Background: 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.Methods: 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.Results: 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.Conclusion: 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."

基金机构：National Natural Science Foundation of China [82303035]; Hunan Provincial Natural Science Foundation of China [2021JJ40321]; Science and Technology Innovation Program of Hunan Province [2020RC2065]

基金资助正文：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) .