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甲状腺癌中与免疫细胞浸润模式相关的预后相关标志性ATP结合盒转运蛋白的鉴定与验证

Identification and Validation of Prognostic Related Hallmark ATP-Binding Cassette Transporters Associated With Immune Cell Infiltration Patterns in Thyroid Carcinoma.

作者信息

Wang Lidong, Sun Xiaodan, He Jingni, Liu Zhen

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Postdoctoral Research Workstation, Jilin Cancer Hospital, Changchun, China.

出版信息

Front Oncol. 2022 Jun 28;12:781686. doi: 10.3389/fonc.2022.781686. eCollection 2022.

Abstract

ATP-binding cassette (ABC) transporters are a large superfamily of membrane proteins that facilitate the translocation of heterogeneous substrates. Studies indicate that ABC transporters may play important roles in various carcinomas. However, the correlation between ABC transporters and immunomodulation in thyroid carcinoma (TC), as well as the prognoses for this disease, is poorly understood.TC data from The Cancer Genome Atlas (TCGA) database were used to identify prognostic hallmark ABC transporters associated with immune cell infiltration patterns multiple bioinformatic analyses. Thereafter, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression of these selected hallmark ABC transporters in both TC and para-cancerous thyroid tissues. Of a total of 49 ABC transporters, five (, , , , and ) were identified as hallmark ABC transporters. All five were differentially expressed in TC and associated with the relapse-free survival rates of patients with TC. Immunoregulation by these five hallmark ABC transporters involved the modulation of various aspects of immune cell infiltration, such as hot or cold tumor subsets and the abundances of infiltrating immune cells, as well as specific immunomodulators and chemokines. Besides the diverse significantly correlated factors, the five hallmark ABC transporters and correlated genes were most highly enriched in plasma membrane, transporter activity, and transmembrane transport of small molecules. In addition, many chemicals, namely bisphenol A and vincristine, affected the expression of these five transporters. The qRT-PCR results of collected TC and para-cancerous thyroid tissues were consistent with those of TCGA. The findings in this study may reveal the role played by these five hallmark ABC transporters in regulating immune cell infiltration patterns in TC as well as the molecular mechanisms underlying their functions, leading to a better understanding of their potential prognostic and immunotherapeutic values.

摘要

ATP结合盒(ABC)转运蛋白是一大类膜蛋白超家族,可促进异质底物的转运。研究表明,ABC转运蛋白可能在各种癌症中发挥重要作用。然而,ABC转运蛋白与甲状腺癌(TC)免疫调节之间的相关性以及该疾病的预后情况,目前仍知之甚少。利用来自癌症基因组图谱(TCGA)数据库的TC数据,通过多项生物信息学分析来识别与免疫细胞浸润模式相关的预后标志性ABC转运蛋白。此后,进行定量实时聚合酶链反应(qRT-PCR)以验证这些选定的标志性ABC转运蛋白在TC组织和癌旁甲状腺组织中的表达。在总共49种ABC转运蛋白中,有5种(、、、和)被确定为标志性ABC转运蛋白。这5种转运蛋白在TC中均有差异表达,并与TC患者的无复发生存率相关。这5种标志性ABC转运蛋白的免疫调节作用涉及免疫细胞浸润各个方面的调节,如热或冷肿瘤亚群、浸润免疫细胞的丰度,以及特定的免疫调节剂和趋化因子。除了多种显著相关因素外,这5种标志性ABC转运蛋白及相关基因在质膜、转运蛋白活性和小分子跨膜转运方面的富集程度最高。此外,许多化学物质,即双酚A和长春新碱,会影响这5种转运蛋白的表达。收集的TC组织和癌旁甲状腺组织的qRT-PCR结果与TCGA的结果一致。本研究结果可能揭示这5种标志性ABC转运蛋白在调节TC免疫细胞浸润模式中所起的作用及其功能的分子机制,从而更好地了解它们潜在的预后和免疫治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2705/9273952/fec3bd43d5d2/fonc-12-781686-g001.jpg

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