Appraising the effectiveness of immune cells on thyroid cancer: a Mendelian randomization study.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2024-07-22 DOI:10.1007/s12020-024-03956-4

Muge Liu, Ling Jin, Xiongsheng Xiao, Siyi Li, Changwei Zheng, Zhengde Chen, Zhi Zhang

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Abstract

Background: The intricate interplay between the immune system and tumor plays a pivotal role in thyroid cancer (TC) pathogenesis, potentially influencing both the causation and therapeutic outcomes. Despite extensive research, existing literature offers ambiguous insights regarding the association between immune cell traits and thyroid cancer progression.

Methods: To elucidate the potential causal relationships, we conducted an integrated two-sample Mendelian randomization (MR) analysis. This study utilized publicly genetic datasets to explore the causalities between 731 immune cell traits (categorized into four trait types across seven panels) and thyroid cancer. We ensured the robustness of our findings through comprehensive sensitivity analyses, meticulously assessing potential sources of bias such as pleiotropy.

Results: After False Discovery Rate (FDR) correction, six immune cell traits were identified to be significantly associated with thyroid cancer risk (Inverse Variance Weighted, IVW): Absolute count of gamma delta T cells/ T-cell receptor gamma delta absolute count (TCRgd AC) 0.8464 (OR95% CI = 0.7477-0.9580, P = 0.0083, PFDR = 0.0103); CD8 on bright CD8 cells (CD8 on CD8br) 0.8867 (OR95% CI = 0.8159-0.9637, P = 0.0047, P_FDR = 0.0093); CD127 on CD45RA negative CD4 T cells not regulatory T cells (CD127 on CD45RA- CD4 not Treg) 0.8969 (OR95% CI = 0.8192-0.9820, P = 0.0186, P_FDR = 0.0186); CD80 on CD62L positive plasmacytoid dendritic cells (CD80 on CD62L+ plasmacytoid DC) 1.1091 (OR95% CI = 1.0267-1.1982, P = 0.0086, P_FDR = 0.0103); CD80 on plasmacytoid DC 1.1283 (OR95% CI = 1.0462-1.2168, P = 0.0017, P_FDR = 0.0093); Side scatter-area on bright CD8 cells (SSC - A on CD8br) 1.1622 (OR95% CI = 1.0507-1.2854, P = 0.0035, P_FDR = 0.0093).

Conclusions: Our study demonstrated the causalities between immune cell traits and thyroid cancers by Mendelian randomization study, thus guiding future mechanism studies.

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评估免疫细胞对甲状腺癌的疗效：孟德尔随机研究。

背景：免疫系统与肿瘤之间错综复杂的相互作用在甲状腺癌（TC）的发病机制中起着关键作用，可能会影响病因和治疗结果。尽管进行了广泛的研究，但现有文献对免疫细胞特征与甲状腺癌进展之间的关联提供了模糊的见解：为了阐明潜在的因果关系，我们进行了综合双样本孟德尔随机化（MR）分析。这项研究利用公开的遗传数据集探讨了 731 个免疫细胞性状（分为四个性状类型，横跨七个面板）与甲状腺癌之间的因果关系。我们通过全面的敏感性分析确保了研究结果的稳健性，细致评估了潜在的偏倚来源，如多效性：结果：经过假发现率（FDR）校正后，发现六种免疫细胞特征与甲状腺癌风险显著相关（逆方差加权，IVW）：γ-δT细胞绝对计数/T细胞受体γ-δ绝对计数（TCRgd AC）0.8464（OR95% CI = 0.7477-0.9580，P = 0.0083，PFDR = 0.0103）；亮CD8细胞上的CD8（CD8 on CD8br）0.8867（OR95% CI = 0.8159-0.9637，P = 0.0047，PFDR = 0.0093）；CD45RA 阴性 CD4 T 细胞而非调节性 T 细胞上的 CD127（CD45RA- CD4 not Treg 上的 CD127）0.8969（OR95% CI = 0.8192-0.9820，P = 0.0186，PFDR = 0.0186）；CD62L 阳性浆细胞树突状细胞上的 CD80（CD62L+ 浆细胞 DC 上的 CD80）1.1091（OR95% CI = 1.0267-1.1982，P = 0.0086，PFDR = 0.0103）；浆细胞 DC 上的 CD80 1.1283（OR95% CI = 1.0462-1.2168，P = 0.0017，PFDR = 0.0093）；亮CD8细胞上的侧散射区（SSC - A on CD8br）1.1622（OR95% CI = 1.0507-1.2854，P = 0.0035，PFDR = 0.0093）.结论：我们的研究通过孟德尔随机研究证明了免疫细胞特质与甲状腺癌之间的因果关系，从而为未来的机制研究提供了指导。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.