LRP11在肝细胞癌中的表达与临床病理参数及预后关系的研究
Journal: Basic Medical Theory Research DOI: 10.32629/bmtr.v8i1.18579
Abstract
目的：研究低密度脂蛋白受体相关蛋白11(low density lipoprotein receptor-related protein 11,LRP11)在肝细胞癌(Hepatocellular carcinoma,HCC)中的表达情况,并分析其与临床病理参数及预后的关联性,为HCC预后评估提供理论依据。方法：①运用免疫组化技术检测85例HCC组织及其癌旁组织中LRP11蛋白的表达量,并探究其与临床病理参数的潜在联系,通过Log-Rank检验分析LRP11表达水平与总生存期(Overall Survival,OS)和无病生存期(Disease-free survival,DFS)的相关性。②Western Blot实验和RT-qPCR实验分别测定新鲜HCC组织及配对远癌旁肝组织中LRP11蛋白和mRNA的表达水平。结果：①免疫组化结果显示LRP11在HCC中的平均光密度值显著低于癌旁组织(0.153(0.13,0.198)VS 0.2(0.171,0.232),P＜0.0001),LRP11低表达与高组织学分级(χ2=3.979,P=0.046)、乙肝阳性(χ2=4.753,P=0.029)、高级别MVI(χ2=3.241,P=0.001)以及有卫星结节(χ2=3.925,P=0.048)相关,Log-Rank检验显示LRP11低表达组患者的OS及DFS较高表达组患者显著缩短(P＜0.0001),COX比例风险回归模型分析显示LRP11低表达是影响HCC患者OS(HR=4.069,P＜0.0001)和DFS(HR=2.885,P=0.002)的独立危险因素。②Western Blot实验显示LRP11蛋白在HCC组织的平均表达水平显著低于癌旁组织(1.54±0.86 VS 2.01±1.27,P= 0.032)；LRP11 mRNA在HCC组织中则表现为高表达(1.83(0.66,5.5)VS 1.02(1.005,1.03),P=0.0172)。结论：LRP11蛋白在HCC中的表达呈下调趋势,且其低表达与HCC不良的预后密切相关,提示LRP11可能成为HCC评估预后的重要参考因子。
Keywords
低密度脂蛋白受体相关蛋白11；肝细胞癌；临床病理参数；预后
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[3] Han BF,Zheng RS, Zeng HM, et al. Cancer incidence and mortality in China,2022[J].Journal of the National Cancer Cen ter,2024,46(3):221-231.
[4] Previn Ganesan, Laura M Kulik.Hepatocellular Carcino ma:New Developments[J].Clin Liver Dis,2023,27(1):85-102.
[5] Tony Dazhong Huang,Jason Behary,Amany Zekry.Nonalcoholic fatty liver disease: a review of epidemiology, risk factors, diagnosis and management[J].Intern Med J,2020,50(9):1038-1047.
[6] 王颖.LRP11在宫颈癌发生发展中的作用及机制研究[D].山东:山东大学,2019.
[7] Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor[J].Clin. Invest,2002,108(6):779-784.
[8] Ju W,Zheng R,Zhang S,et al. Cancer statistics in Chinese older people,2022:current burden, time trends,and compariso ns with the US, Japan, and the Republic of Korea[J]. Sci China Life Sci,2023,66(5):1079-1091.
[9] Gan S, Ye J, Li J, et al. LRP11 activates β-catenin to induce PD-L1 expression in prostate cancer[J]. J Drug Target, 2020,28(5):508-515.
[10] 米卫国,张伟,刘建军,等.低密度脂蛋白受体相关蛋白LRP11在乳腺癌组织中的表达水平及生物学意义[J].中国妇幼保健,2021,36(21):5053-5056.
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[13] Pei J, Wang H, Zhang Y, et al. The Role of Low-Density Lipoprotein Receptor-Associated Protein LRP11 in the Devel opment of Hepatocellular Carcinoma[J].SCI ADV MATER,2023,15(7):972-978.
[14] Yoo W, Kim AK, Kook HU. Comprehensive analysis on clinical significance and therapeutic targets of LDL receptor related protein 11(LRP11)in liver hepatocellular carcinoma [J].Front Pharmacol,2024,15:1338929.
[15] Sun L, Ma Z, Zhao X, et al. LRP11 promotes stem-like T cell via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy[J].J Immunother Cancer,2024,12(1):1-16.
[16] 李建凯,朱小辉,何佳欣,等.低密度脂蛋白受体相关蛋白11在结直肠癌组织中的表达及其对SW480细胞增殖和凋亡的影响[J].中国肿瘤生物治疗杂志,2023,30(9):771-776.
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[18] Gu F,Xu F,Pan Z,et al.An integrative pan-cancer analy sis illustrating the key role of LRP11 in cervical cancer[J]. Medicine,2023,102(11):e33201.
[19] Zhou Y,Zhao Y,Gao Y,et al.Hepatitis C virus NS3 protein enhances hepatocellular carcinoma cell invasion by promoting PPM1A ubiquitination and degradation[J]. J Exp Clin Cancer Res,2017,36(1):42.
[20] Zhang L,Chen J,Ning D,et al.FBXO22 promotes the devel opment of hepatocellular carcinoma by regulating the ubiqu itination and degradation of p21[J]. J Exp Clin Cancer Res, 2019,38(1):101.
[21] Hang X, Zhu S, Di H, et al. NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN[J]. Cell Physiol Biochem,2016,39(2):768-779.
[22] Huang ZJ, Zhu JJ, Yang XY, et al. NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatoc ellular carcinoma[J].Oncol Lett,2017,14(3):2649-2656.
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