CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.
Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.
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本研究初步描述了原发性 ACP、复发性 ACP 与 RCC 之间的蛋白质组学差异。我们的发现为颅咽管瘤研究人员提供了资源，并可能最终拓展对复发性 ACP 的现有认识并惠及临床实践。
造釉细胞型颅咽管瘤（ACPs）是罕见的良性上皮性肿瘤，具有高复发率和不良预后。复发性和原发性ACP之间可能与疾病复发和治疗相关的生物学差异尚未在蛋白质组水平上进行评估。在本研究中，我们旨在确定配对的复发性和原发性ACP的蛋白质组谱，深入了解ACP复发的生物学机制，并确定ACP治疗的潜在靶点。
在中国北京首都医科大学三博脑科医院接受手术并经病理证实为ACP（n = 15）或Rathke裂囊肿（RCC；n = 7）的患者被纳入本研究。我们进行了蛋白质组学分析，以研究原发性ACP、配对复发性ACP和RCC的特征。采用Western blotting验证我们的蛋白质组学结果，并评估复发性与原发性ACP中关键肿瘤相关蛋白的表达。采用流式细胞术评估原发性和复发性ACP组织样本中TIL（肿瘤浸润淋巴细胞）（TILs）的耗竭情况。对CD3和PD-L1进行免疫组化染色，以确定配对原发性和复发性ACP样本之间T细胞浸润和免疫抑制分子表达的差异。
生物信息学分析显示，复发性和原发性ACP之间差异表达的蛋白质与细胞外基质组织和白细胞介素信号传导显著相关。与原发性ACP相比，复发ACP中组织蛋白酶K表达上调，可能在ACP复发中发挥作用。对ACP的流式细胞术分析揭示了T细胞的高浸润和TIL的耗竭。
Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples.
The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP.
This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.
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