LRRC59在宫颈癌中的表达及预后价值-现代医学

LRRC59在宫颈癌中的表达及预后价值

单位：1. 南京医科大学附属江宁医院妇产科, 江苏南京 211100;
2. 南京医科大学第二附属医院妇产科, 江苏南京 210000

分类号：R737.33

出版年·卷·期（页码）：2024·52·第一期（53-58）

摘要：

目的：评估富含亮氨酸重复序列蛋白59(LRRC59)在宫颈癌组织中的表达及对宫颈癌患者预后的影响，并探讨LRRC59调节宫颈癌发生的机制。方法：GEPIA网站分析LRRC59 mRNA在13例正常宫颈组织和306例宫颈癌组织中的表达水平。实时荧光定量聚合酶链反应检测LRRC59 mRNA在10例正常宫颈组织及12例宫颈癌组织中的表达差异。Kaplan-Meier Plotter数据库分析LRRC59对宫颈癌患者总生存期和无复发生存期的影响。基于TCGA数据库中的转录组数据和临床数据绘制ROC曲线并进行单因素和多因素Cox回归分析。基因集富集分析探究LRRC59调节宫颈癌发生的机制。结果：LRRC59 mRNA在宫颈癌组织中表达增加(P<0.05)。LRRC59高表达的宫颈癌患者总生存期(P=0.022)及无复发生存期(P<0.001)更短。LRRC59对宫颈癌患者预后有一定的诊断价值(3年AUC=0.610,5年AUC=0.633)。LRRC59 高表达是宫颈癌患者预后不良的独立危险因素[HR=2.645，95%CI(1.378～5.078)，P=0.003]。LRRC59通过多条肿瘤相关的信号通路调节宫颈癌的发生。结论：LRRC59在宫颈癌组织中表达增加，LRRC59高表达与宫颈癌患者预后不良相关，可能是宫颈癌新的治疗靶点。

Objective: To evaluate the expression level，prognostic value and potential mechanisms of leucine-rich repeat-containing protein 59(LRRC59) in cervical cancer. Methods: GEPIA database was used to examine the expression level of LRRC59 mRNA in 13 normal cervical tissues and 306 cervical cancer tissues. Real-time quantitative polymerase chain reaction was conducted to detect the expression of LRRC59 mRNA in 10 normal cervical tissues and 12 cervical cancer tissues. Kaplan-Meier Plotter database was used to analyze the relationship between LRRC59 expression and overall survival and relapse-free survival of cervical cancer patients. ROC curve was plotted and univariate and multivariate Cox regression analysis were performed using the transcriptome and clinical data from TCGA database. Gene set enrichment analysis was used to explore the mechanisms of LRRC59 in cervical cancer. Results: The expression of LRRC59 mRNA was increased in cervical cancer tissues compared with normal cervical tissues(P<0.05). The patients with high expression of LRRC59 had a shorter overall survival(P=0.022) and relapse-free survival(P<0.001).LRRC59 had a certain diagnostic value in the prognosis of cervical cancer patients(AUC at 3 years was 0.610,AUC at 5 years was 0.633). The high expression of LRRC59 was an independent risk factor predicting poor prognosis in cervical cancer patients[HR=2.645，95%CI(1.378～5.078)，P=0.003]. LRRC59 regulated the development of cervical cancer through multiple tumor-associated signaling pathways. Conclusion: The expression of LRRC59 mRNA is increased in cervical cancer tissues, and the high expression of LRRC59 is associated with poor prognosis in cervical cancer patients. LRRC59 may be a novel therapeutic target for cervical cancer.

参考文献：

[1] SUNG H,FERLAY J,SIEGEL R L,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2] CHEN Y,ZUO X,WEI Q,et al.Upregulation of LRRC8A by m(5)C modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer[J].Int J Biol Sci,2023,19(2):691-704.
[3] 杨茹，田甜，张靖，等.宫颈癌组织KLK4、STAG2的表达及其临床意义[J].东南大学学报(医学版),2023，42(4)：540-546.
[4] BLENSKI M,KEHLENBACH R H.Targeting of LRRC59 to the endoplasmic reticulum and the inner nuclear membrane[J].Int J Mol Sci,2019,20(2):334-352.
[5] HOFFMAN A M,CHEN Q,ZHENG T,et al.Heterogeneous translational landscape of the endoplasmic reticulum revealed by ribosome proximity labeling and transcriptome analysis[J].J Biol Chem,2019,294(22):8942-8958.
[6] HANNIGAN M M,HOFFMAN A M,THOMPSON J W,et al.Quantitative proteomics links the LRRC59 interactome to mRNA translation on the ER membrane[J].Mol Cell Proteomics,2020,19(11):1826-1849.
[7] ZHEN Y,SORENSEN V,SKJERPEN C S,et al.Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnalpha1 and Kpnbeta1[J].Traffic,2012,13(5):650-664.
[8] PALLAI R,BHASKAR A,BARNETT-BERNODAT N,et al.Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells[J].Tumour Biol,2015,36(8):6383-6390.
[9] DUAN T,ZHOU D,YAO Y,et al.The association of aberrant expression of FGF1 and mTOR-S6K1 in colorectal cancer[J].Front Oncol,2021,11:706838.
[10] SOOFIYANI S R,HEJAZI M S,BARADARAN B.The role of CIP2A in cancer:a review and update[J].Biomed Pharmacother,2017,96:626-633.
[11] 刘宗超，李哲轩，张阳，等.2020全球癌症统计报告解读[J].肿瘤综合治疗电子杂志，2021，7(2):1-14.
[12] LIANG C C,RAZA S H A,SHENGCHEN Y,et al.Bioinformatics role of the WGCNA analysis and co-expression network identifies of prognostic marker in lung cancer[J].Saudi J Biol Sci,2022,29(5):3519-3527.
[13] GENG X,ZHANG Y,ZENG Z,et al.Molecular characteristics,prognostic value,and immune characteristics of m(6)A regulators identified in head and neck squamous cell carcinoma[J].Front Oncol,2021,11:629718.
[14] TODA H,KUROZUMI S,KIJIMA Y,et al.Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures:antitumor miR-204-5p targets AP1S3[J].J Hum Genet,2018,63(12):1197-1210.
[15] TERP M G,LUND R R,JENSEN O N,et al.Identification of markers associated with highly aggressive metastatic phenotypes using quantitative comparative proteomics[J].Cancer Genomics Proteomics,2012,9(5):265-273.
[16] MAURIZIO E,WISNIEWSKI J R,CIANI Y,et al.Translating proteomic into functional data:an high mobility group A1(HMGA1) proteomic signature has prognostic value in breast cancer[J].Mol Cell Proteomics,2016,15(1):109-123.
[17] LI D,XING Y,TIAN T,et al.Overexpression of LRRC59 is associated with poor prognosis and promotes cell proliferation and invasion in lung adenocarcinoma[J].Onco Targets Ther,2020,13:6453-6463.
[18] PEI L,ZHU Q,ZHUANG X,et al.Identification of leucine-rich repeat-containing protein 59(LRRC59) located in the endoplasmic reticulum as a novel prognostic factor for urothelial carcinoma[J].Transl Oncol,2022,23:101474.
[19] 赵尧烨，刘震东，刘润泽，等.LRRC59基因在尤文肉瘤的表达与意义[J].中国矫形外科杂志，2022，30(19)：1786-1790.
[20] KIM J,KANG J,KANG Y L,et al.Ketohexokinase—A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer[J].Nat Commun,2020,11(1):5436.

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