SPRED2 在肺腺癌中的表达

IF 2.9 4区 医学 Q2 PATHOLOGY Pathology, research and practice Pub Date : 2024-11-19 DOI:10.1016/j.prp.2024.155721
Yoko Ota , Tong Gao , Masayoshi Fujisawa , I.Wayan Sumardika , Masakiyo Sakaguchi , Shinichi Toyooka , Teizo Yoshimura , Akihiro Matsukawa
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引用次数: 0

摘要

SPRED2(Sprouty-related, EVH1 domain-containing protein 2)是ERK1/2通路的负调控因子,在多种癌症中被下调;然而,SPRED2在肺腺癌(LUAD)中的表达意义仍不清楚。在此,我们研究了 77 例临床患者的 LUAD 组织中 SPRED2 的病理表达及其与 ERK1/2 活化(ERK1/2 磷酸化)、Ki67 指数和临床病理特征的关系。免疫组化结果显示,与原位腺癌(AIS)相比,浸润性腺癌(IA)中SPRED2的表达减少。SPRED2的表达与pERK1/2水平呈负相关,与Ki67指数呈正相关。在数据库分析中,SPRED2表达量较高的患者的生存概率高于表达量较低的患者。在体外,SPRED2缺失会增加三种LUAD细胞系(A549:KRAS突变、H1993:MET扩增和HCC4006:EGFR突变)的细胞增殖、迁移和侵袭,而SPRED2过表达则会降低这些反应。因此,SPRED2似乎是LUAD进展的调控因子,也是治疗LUAD的潜在靶点。
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Expression of SPRED2 in the lung adenocarcinoma
SPRED2 (Sprouty-related, EVH1 domain-containing protein 2), a negative regulator of the ERK1/2 pathway, is downregulated in several cancers; however, the significance of SPRED2 expression in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the pathological expression of SPRED2 and its relationship with ERK1/2 activation (ERK1/2 phosphorylation), Ki67 index and clinicopathological features in 77 LUAD tissues from clinical patients. Immunohistochemically, SPRED2 expression was decreased in invasive adenocarcinoma (IA) compared to adenocarcinoma in situ (AIS). There was a negative correlation between SPRED2 expression and pERK1/2 levels and a positive correlation between SPRED2 expression and Ki67 index. In the database analysis, the survival probability was higher in patients with higher SPRED2 expression than in those with lower expression. In vitro, SPRED2 deletion increased cell proliferation, migration and invasion of three LUAD cell lines (A549:KRAS mutation, H1993:METamplification, and HCC4006:EGFR mutation), whereas SPRED2 overexpression decreased these responses. Thus, SPRED2 appears to be a regulator of LUAD progression and a potential target for the treatment of LUAD.
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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