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多组学分析揭示了层黏蛋白聚糖在多种癌症类型中的预后价值和肿瘤微环境价值。

Multi-omics analysis reveals the prognostic and tumor micro-environmental value of lumican in multiple cancer types.

作者信息

Guo Zehuai, Li Zeyun, Chen Ming, Qi Xiangjun, Sun Zhe, Wu Siqi, Hou Xuenan, Qiu Mengli, Cao Yang

机构信息

Department of Internal Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China.

Guangzhou Huaxia Vocational College, Guangzhou, China.

出版信息

Front Mol Biosci. 2023 Aug 24;10:1158747. doi: 10.3389/fmolb.2023.1158747. eCollection 2023.

Abstract

Lumican (LUM), a proteoglycan of the extracellular matrix, has been reported to be involved in the regulation of immune escape processes, but the data supporting this phenomenon are not sufficient. In this study, we aimed to explore the links among LUM expression, survival, tumor microenvironment (TME), and immunotherapy in 33 cancer types. Data from several databases, such as UCSC Xena, GTEx, UALCAN, HPA, GEPIA2, TISIDB, PrognoScan, TIMER2, and GEO, as well as published studies, were used to determine the relationship between LUM expression and clinical features, TME, heterogeneity, and tumor stemness. The expression of LUM was statistically different in most tumors versus normal tissues, both at the RNA and protein expression levels. High expression of LUM was typically associated with a poor prognosis in tumors. Additionally, immune scores, six immune cells, four immunosuppressive cells, cancer-associated fibroblasts (CAFs)-associated and immunosuppressive factors, tumor mutation burden (TMB), microsatellite instability (MSI), DNAss, and RNAss were all significantly associated with LUM. Among them, LUM expression displayed a significant positive correlation with CAFs and their factors, and exhibited immunosuppressive effects in six independent immunotherapy cohorts. Multi-omics analysis suggests that LUM may have been a prognostic marker, contributed to immunosuppression in the TME, and decreased the effectiveness of immune checkpoint inhibitors.

摘要

亮氨酸富含蛋白聚糖(LUM)是一种细胞外基质蛋白聚糖,据报道其参与免疫逃逸过程的调控,但支持这一现象的数据并不充分。在本研究中,我们旨在探究33种癌症类型中LUM表达、生存、肿瘤微环境(TME)和免疫治疗之间的联系。来自多个数据库的数据,如UCSC Xena、GTEx、UALCAN、HPA、GEPIA2、TISIDB、PrognoScan、TIMER2和GEO,以及已发表的研究,被用于确定LUM表达与临床特征、TME、异质性和肿瘤干性之间的关系。LUM的表达在大多数肿瘤与正常组织之间,无论是在RNA还是蛋白质表达水平上,均存在统计学差异。LUM的高表达通常与肿瘤预后不良相关。此外,免疫评分、六种免疫细胞、四种免疫抑制细胞、癌症相关成纤维细胞(CAF)相关和免疫抑制因子、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、DNAss和RNAss均与LUM显著相关。其中,LUM表达与CAF及其因子呈显著正相关,并在六个独立的免疫治疗队列中表现出免疫抑制作用。多组学分析表明,LUM可能是一种预后标志物,在TME中促成免疫抑制,并降低免疫检查点抑制剂的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a93/10484533/037aa1d97860/fmolb-10-1158747-g001.jpg

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