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CLDN1和EGFR在甲状腺乳头状癌中的表达

Expression of CLDN1 and EGFR in PTC.

作者信息

Wu JunJie, Wang YouMei, Yan Lei, Dong YaWen

机构信息

Department of Pathology, the First People's Hospital of Pinghu, Jiaxing, Zhejiang, People's Republic of China.

出版信息

Discov Oncol. 2024 Oct 15;15(1):562. doi: 10.1007/s12672-024-01428-9.

Abstract

Papillary thyroid carcinoma (PTC) involves complex genetic mechanisms, notably involving CLDN1 and EGFR. This study investigates the expression and variations of these genes and their effects on tumor behavior and patient outcomes. Meta-analysis of CLDN1 and EGFR expression in TCGA-PTC patients and GEO datasets was conducted. cBioPortal was used for clinical analysis. GSEA, GO, KEGG, Hallmark pathways, and cibersort analysis were applied. Cell proliferation, migration, invasion, and apoptosis were assessed in vitro. Co-culturing with CD8 T cells, MTT assay, ELISA, subcutaneous tumor models, and immunohistochemistry were performed. TGF-β pathway-related proteins were analyzed via Western blot. CLDN1 and EGFR were overexpressed in PTC tumors, correlating with higher-risk patients and reduced CD8 T cell infiltration. Silencing these genes inhibited tumor cell functions and enhanced CD8 T cell activity, both in vitro and in vivo. CLDN1 and EGFR are crucial in PTC, linked to tumor invasiveness, EMT, and immune suppression, presenting them as potential therapeutic targets.

摘要

甲状腺乳头状癌(PTC)涉及复杂的遗传机制,尤其涉及紧密连接蛋白1(CLDN1)和表皮生长因子受体(EGFR)。本研究调查了这些基因的表达和变异及其对肿瘤行为和患者预后的影响。对TCGA-PTC患者和GEO数据集中CLDN1和EGFR的表达进行了荟萃分析。利用cBioPortal进行临床分析。应用了基因集富集分析(GSEA)、基因本体论(GO)、京都基因与基因组百科全书(KEGG)、标志性通路和细胞类型鉴定通过估计相对子集RNA转录本(cibersort)分析。在体外评估细胞增殖、迁移、侵袭和凋亡。进行了与CD8 T细胞共培养、MTT法、酶联免疫吸附测定(ELISA)、皮下肿瘤模型和免疫组织化学实验。通过蛋白质免疫印迹法分析转化生长因子-β(TGF-β)通路相关蛋白。CLDN1和EGFR在PTC肿瘤中过表达,与高危患者相关,并减少CD8 T细胞浸润。在体外和体内,沉默这些基因均抑制肿瘤细胞功能并增强CD8 T细胞活性。CLDN1和EGFR在PTC中至关重要,与肿瘤侵袭性、上皮-间质转化(EMT)和免疫抑制相关,表明它们是潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aa1/11480332/2cac74fcfca0/12672_2024_1428_Fig1_HTML.jpg

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