LYPD1, 一种免疫细胞浸润调控因子参与卵巢癌的不良预后  

Lypd1,a regulator of immune cell infiltration,is involved in poor prognosis of ovarian cancer

作　　者：于歌 刘树民[1] 冯晓玲[3] Yu Ge;Liu Shumin;Feng Xiaoling(Institute of Traditional Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Department of Gynecology,Harbin Medical University Cancer Hospital,Harbin 150081,China;Department of Gynecology,the First Afiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学药学院,哈尔滨150040 [2]哈尔滨医科大学附属肿瘤医院妇科,哈尔滨150081 [3]黑龙江中医药大学附属第一医院妇科,哈尔滨150040

出　　处：《国际遗传学杂志》2022年第4期255-264,共10页International Journal of Genetics

基　　金：黑龙江省博士后基金(LBH-Z19215);黑龙江省中医药管理局基金(ZHY2020-173)。

摘　　要：目的探究Ly6/Plaur结构域包含蛋白1(Ly6/Plaur domain-containing 1,LYPD1)在卵巢癌中的作用、潜在机制以及与卵巢癌患者不良预后的关系。方法癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据中分析不同癌症中LYPD1的表达。同时,以TCGA数据库中卵巢癌患者临床生存数据评价LYPD1对卵巢癌患者预后的影响。采用Metascape数据库对LYPD1在卵巢癌生物学功能进行富集分析。CCK-8方法检测细胞增殖活性,流式细胞术检测细胞凋亡。Western印迹方法检测低表达LYPD1后对于SKOV3和A2780细胞中NF-κB蛋白的影响。肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库分析LYPD1对于卵巢癌免疫细胞浸润的影响。结果LYPD1在卵巢癌中高表达,且在卵巢癌中的总生存率较低,同时LYPD1与疾病特异性生存率和无进展期相关。此外,低表达LYPD1能够抑制卵巢癌细胞增殖活性,诱导凋亡。I-κB激酶/NF-κB信号通路是LYPD1参与卵巢癌恶性进展的潜在通路之一。低表达LYPD1使卵巢癌细胞SKOV3和A2780中NF-κB蛋白表达升高。且LYPD1的表达与卵巢癌免疫细胞浸润密切相关。如,T细胞(P=0.041,r=0.100),DC细胞(P=0.034,r=0.110)以及巨噬细胞(P=0.027,r=0.110)表达正相关,与Tgd(P=0.001,r=-0.180),以及NK细胞(P=0.044,r=-0.100)负相关。结论LYPD1是一个原癌基因,通过I-κB激酶/NF-κB调控免疫细胞浸润参与卵巢癌细胞的异常增殖以及卵巢癌患者不良预后。Objective To explore the role and potential mechanism of Ly6/Plaur domain-containing 1(LYPD1)in ovarian cancer and its relationship with poor prognosis of ovarian cancer patients.Methods LYPD1 expression was analyzed in the cancer genome atlas(TCGA)pan-cancer data.The influence of LYPDI on clinical prognosis was evaluated by clinical survival data of TCGA.The biological function of LYPD1 in ovarian cancer was enriched and analyzed by Metascape database.Cell viability was detected by CCK-8 and cell apoptosis was detected by Flow cytometry.Western blot was used to detect protein level of NF-κB in SKOV3 and A2780 cells after lowering expression of LYPD1.The effect of LYPD1 on immune cells of ovarian cancer was analyzed by tumor immune estimation resource(TIMER)database.Results LYPD1 is highly expressed in OV and the overall survival rate in OV is low,which is related to disease-specific survival and progression free period.In addition,low expression of LYPD1 can inhibit the proliferation of ovarian cancer,reduce its activity,and induce apoptosis.I-κB kinase/NF-κB signaling pathway is one of the potential pathways for LYPD1 to participate in the malignant progression of ovarian cancer.Low expression of LYPD1 increases NF-κB protein expression in SKOV3 and A2780 cells increased.Moreover,the expression of LYPD1 is closely related to the infiltration of immune cells in ovarian cancer such as T cells(P=0.041,r=0.100),DC cells(P=0.034,r=0.110),macrophages(P=0.027,r=0.110),TGD(P=0.001,r=-0.180)and NKcells(P=0.044,r=-0.100).Conclusion Our study suggests that LYPD1 is an oncogene and acts as an indicator of poor prognosis in ovarian cancer.

关 键 词：Ly6/Plaur结构域包含蛋白1 卵巢癌 NF-ΚB 免疫细胞浸润 

分 类 号：R737.31[医药卫生—肿瘤]