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A Novel Prognostic Biomarker lpar6 in Hepatocellular Carcinoma via Associating with Immune Infiltrates

Journal of Clinical and Translational Hepatology 2022年第1期10卷 90-103页

作者： Jian He Mei Meng Hui Wang State Key Laboratory of Oncogenes and Related Genes Center for Single-Cell OmicsSchool of Public HealthShanghai Jiao Tong University School of MedicineShanghaiChina

Background and Aims:lpar6 is the most recently deter-mined G protein-coupled receptor of lysophosphatidic acid,and hardly any study has demonstrated the performance of lpar6 in *** sought to clarify the relationship of lpar6 to prognosis potential and tumor infiltration im-mune cells in different ***:The expression of lpar6 and its clinical characteristics were evaluated on various *** association between lpar6 and im-mune infiltrates of various types of cancer were investigated via ***:We determined that higher lpar6 ex-pression level was associated with a better overall ***,high lpar6 expression level was significantly associated with better disease-specific survival(DSS)in bladder cancer,and better overall survival(OS)/progres-sion-free survival(PFS)/distant metastasis-free survival(DMFS)/relapse-free survival(RFS)in breast cancer and some other types of ***,lpar6 significant-ly affects the prognosis of various cancers via The Cancer Genome Atlas(TCGA).Further research exposed that the mRNA level of lpar6 was positively coordinated with in-filtrating levels of devious immune cells in hepatocellular ***:Our results imply that lpar6 is associated with prognosis potential and immune infiltration levels in liver ***,lpar6 expression possibly contributes to the activation of CD8+T,naive T,effector T cells and natural killer cells and inactivates T regulatory cells,decreases T cell exhaustion and regulate T helper cells in liver *** discoveries imply that lpar6 could be a novel biomarker of prognosis for indicating progno-sis potential and immune-infiltrating level in hepatocellular carcinoma.

关键词： lpar6 TILs Prognosis Hepatocellular carcinoma Biomarker

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lpar6在乳腺癌中的表达与潜在调控机制探讨

LPAR6在乳腺癌中的表达与潜在调控机制探讨

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作者：陶凯重庆医科大学

学位级别：硕士

目的:溶血磷脂酸受体6(Lysophosphatidic acid receptor6,lpar6)是溶血磷脂酸(LPA)的新发现受体,近期的研究提示lpar6可能参与到部分肿瘤的生物学行为过程中。来自Oncomine和Gene Expression Omnibus(GEO)数据库的数据表明乳腺癌(Breast cancer,BC)组织中lpar6的表达相对于正常组织表达显著降低,然而lpar6的功能和机制在乳腺癌却未见报道。因此,本研究的目的在于评估lpar6在乳腺癌患者中的表达水平,分析表达水平与患者预后的关系;并进一步探讨lpar6表达调控的潜在机制,预测lpar6在乳腺癌中可能的生物学功能。方法:我们总共收集98对新鲜冷冻的临床乳腺癌标本和配对的癌旁组织,使用液氮进行保存,供随后RNA提取。同时,使用人乳腺癌细胞系进行体外实验。使用定量实时聚合酶链式反应(qRT-PCR)以及蛋白免疫印迹技术(Western Blotting,WB)来评估lpar6在临床标本和BC细胞系的表达水平,并且使用数据库的数据再次验证。然后进一步分析lpar6表达与乳腺癌病理分子分型等参数的关系,同时使用Kaplan-Meier曲线对数据库中差异表达lpar6的乳腺癌患者进行生存分析。此外,我们分析lpar6在乳腺癌中可能受甲基化调控;因此,我们使用特异性去甲基化药物地西他滨(5-氮杂-2'-脱氧胞苷,5-Aza)对细胞系进行干预,检验其中lpar6的表达是否上调。最后,利用生物信息学方法,预测lpar6在肿瘤中的功能和潜在作用机制。结果:与癌旁组织相比,癌组织中lpar6的表达显著降低(plpar6水平,预示患者获得更好的预后(plpar6表达的关系,我们发现lpar6表达水平与乳腺癌分子分型(plpar6基因的启动子区域在癌组织中呈相对高甲基化状态(plpar6表达水平。结合临床标本验证和数据库芯片分析结果,lpar6可能通过调节性激素依赖信号通路参与乳腺癌的发生发展。结论:lpar6在乳腺癌组织中表达明显下调,低表达的lpar6可能预示着不良预后。lpar6的表达水平受基因甲基化调控,并且可能通过性激素依赖通路影响乳腺癌生物学行为。

关键词：乳腺癌 lpar6 预后甲基化

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Lysophosphatidic acid receptor 6 is a potential biomarker associated with lung adenocarcinoma

Lysophosphatidic acid receptor 6 is a potential biomarker as...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者： Jian He Rui Gao Mei Meng Hui Wang 上海交通大学医学院

lpar6 is the most recently determined G-protein-coupled receptor of lysophosphatidic acid receptor, and very few of study have demonstrated the performance of lpar6 in cancers. Moreover, the relationship of lpar6 to the potential of prognosis and tumor infiltration immune cells in different types of cancer is still unclarified. The mR NA expression of lpar6 and its clinical characteristics were evaluated on various databases. The association between lpar6 and immune infiltrates of various types of cancer were investigated via TIMER. IHC for lpar6 in lung adenocarcinoma（LUAD） and lung squamous cell carcinoma（LUSC） tissue microarray with patients’ information was detected. We constructed a systematic prognostic landscape in a variety types of cancer base on the expression level of mRNA. We enclosed that higher lpar6 mR NA expression level was associated with better overall survival in some types of malignancy. Moreover, lpar6 significantly affects the prognostic potential of various cancers in TCGA, especially in lung cancer. Tissue microarray’s results demonstrated that a higher protein level of lpar6 was correlated to better overall survival of LUAD rather than LUSC cohorts. Further research found that the underlying mechanism of this phenome might be the mR NA expression level of lpar6 was positively associated to infiltrating statuses of devious immunocytes in LUAD rather than in LUSC, that is, lpar6 expression potentially contributes to the activation and recruiting of T cells（CD8+ T, naive T, effector T cell） and NK cells and inactivates Tregs, decrease T cell exhaustion and regulate T-helper cells in LUAD. Our discovery implies that lpar6 is associated with prognostic potential and immune-infiltrating levels in *** discoveries imply that lpar6 could be a novel promising biomarker for indicating the prognosis potential of LUAD patients.

关键词： lpar6 tumor infiltration lymphocytes prognosis lung adenocarcinoma biomarker

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