ARPP19表达与鼻咽癌患者临床病理特征及预后的相关性分析-东南大学学报医学版

ARPP19表达与鼻咽癌患者临床病理特征及预后的相关性分析

单位：1. 河南科技大学第一附属医院耳鼻喉科/河南科技大学临床医学院, 河南洛阳 471003;
2. 郑州大学附属洛阳市中心医院眼科, 河南洛阳 471003

分类号：R739.6

出版年·卷·期（页码）：2023·42·第四期（590-595）

摘要：

目的:探讨环腺苷酸调节的磷酸化蛋白-19(ARPP19)表达与鼻咽癌患者临床病理特征及预后的相关性。方法:选取2015年5月至2017年6月河南科技大学第一附属医院收治的74例鼻咽癌患者的鼻咽癌组织与癌旁组织标本,采用qRT-PCR检测ARPP19 mRNA的表达,免疫组化染色检测ARPP19蛋白表达水平,分析ARPP19与鼻咽癌患者临床病理特征的相关性,Kaplan-Meier生存曲线分析ARPP19与鼻咽癌患者预后的相关性,Cox回归模型分析影响鼻咽癌患者总生存期的危险因素。结果:ARPP19 mRNA在鼻咽癌组织表达水平为2.41±0.25,显著高于癌旁组织的1.05±0.12(t=35.750,P＜0.001)。ARPP19蛋白主要定位于细胞质或细胞膜,少量定位于细胞核,呈棕色或棕褐色。ARPP19蛋白在鼻咽癌组织阳性表达率为64.86%,显著高于癌旁组织的21.62%(P＜0.001)。TNM分期Ⅲ~Ⅳ期和有淋巴结转移的患者ARPP19阳性表达率显著高于TNM分期Ⅰ~Ⅱ期和无淋巴结转移的患者(P＜0.05);不同性别、年龄、吸烟史、肿瘤分化程度及神经侵犯的患者ARPP19阳性表达差异均无统计学意义(P＞0.05)。Kaplan-Meier生存分析显示,ARPP19阳性表达组5年生存率为43.75%(21/48),低于阴性表达组的76.92%(20/26)(χ²=7.906,P=0.004)。TNM分期(HR=3.255,95%CI:2.025~5.234,P=0.003)、淋巴结转移(HR=2.614,95%CI:1.351~5.056,P=0.007)、ARPP19阳性表达(HR=2.716,95%CI:1.854~3.978,P=0.003)是影响鼻咽癌患者总生存期的独立危险因素(P＜0.05)。结论:鼻咽癌组织ARPP19呈高表达,且与TNM分期、淋巴结转移及患者预后有关,对鼻咽癌患者预后评估有一定临床意义。

Objective: To explore the correlation between the expression of cyclic adenylate regulated phosphorylated protein 19(ARPP19) and the clinicopathological characteristics and prognosis of nasopharyngeal carcinoma patients. Methods: The nasopharyngeal and paracancer tissue samples of 74 patients with nasopharyngeal carcinoma admitted to our hospital from May 2015 to June 2017 were selected. The expression of ARPP19 mRNA was detected by qRT-PCR, and the expression of ARPP19 protein was detected by immunohistochemical staining. The correlation between ARPP19 and clinicopathological characteristics of patients with nasopharyngeal carcinoma was analyzed, and the correlation between ARPP19 and prognosis of patients with nasopharyngeal carcinoma was analyzed by Kaplan-Meier survival curve, the risk factors affecting the overall survival of patients with nasopharyngeal carcinoma was analyzed by Cox regression model. Results: The expression level of ARPP19 mRNA in nasopharyngeal carcinoma tissues was 2.41±0.25, which was significantly higher than that in adjacent tissues(1.05±0.12)(t=35.750, P<0.001), ARPP19 protein was mainly located in the cytoplasm or cell membrane, with a small amount of ARPP19 protein located in the nucleus, which was brown or tan, the positive expression rate of ARPP19 in nasopharyngeal carcinoma tissues was 64.86%, which was significantly higher than that in adjacent tissues(21.62%)(P<0.001). The positive expression rate of ARPP19 in patients with TNM stage Ⅲ-Ⅳ and lymph node metastasis was obviously higher than that in patients with TNM stage Ⅰ-Ⅱ and no lymph node metastasis(P<0.05). There was no significant difference in the positive expression of ARPP19 among patients with different gender, age, smoking history, tumor differentiation degree and nerve invasion(P>0.05). Kaplan-Meier survival analysis showed that the 5-year survival rate of ARPP19 positive expression group was 43.75%(21/48), which was lower than 76.92%(20/26) of negative expression group(χ²=7.906, P=0.004). TNM stage(HR=3.255, 95%CI:2.025-5.234, P=0.003), lymph node metastasis (HR=2.614, 95%CI:1.351-5.056, P=0.007), and ARPP19 positive expression(HR=2.716, 95%CI:1.854-3.978, P=0.003) were independent risk factors affecting the overall survival of patients with nasopharyngeal carcinoma (P<0.05). Conclusion: ARPP19 is highly expressed in nasopharyngeal carcinoma tissues, and related to TNM stage, lymph node metastasis and prognosis of patients, which has certain clinical significance for the prognosis evaluation of patients with nasopharyngeal carcinoma.

参考文献：

[1] BOSSI P,CHAN A T,LICITRA L,et al.Nasopharyngeal carcinoma:ESMO-EURACAN Clinical Practice Guidelines for diagnosis,treatment and follow-up[J].Ann Oncol,2021,32(4):452-465.
[2] 尹艳辉,吴爱军,周玲芝.鼻咽癌患者miR-214-3p表达意义及与预后的关系分析[J].现代医学,2022,50(8):974-979.
[3] YU Y,LAI S,PENG X.Long non-coding RNA MCM3AP-AS1 facilitates colorectal cancer progression by regulating the microRNA-599/ARPP19 axis[J].Oncol Lett,2021,21(3):225-242.
[4] SONG H,PAN J,LIU Y,et al.Increased ARPP-19 expression is associated with hepatocellular carcinoma[J].Int J Mol Sci,2014,16(1):178-192.
[5] YIN X,GU X,LI F,et al.LncRNA SNHG6 accelerates nasopharyngeal carcinoma progression via modulating miR-26a-5p/ARPP19 axis[J].Bioorg Med Chem Lett,2021,40(1):1-8.
[6] 王波涛,赵琳,夏翠,等.鼻咽癌组织中BMAL1和CerbB-2基因的表达及机制[J].西安交通大学学报(医学版),2021,42(1):65-69.
[7] ZHU Q,ZHANG Q,GU M,et al.MiR106A-5p upregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma[J].Autophagy,2021,17(7):1667-1683.
[8] HACHED K,GOGUET P,CHARRASSE S,et al.ENSA and ARPP19 differentially control cell cycle progression and development[J].J Cell Biol,2019,218(2):541-558.
[9] XIA X,ZHANG H,XIA P,et al.Identification of glycolysis-related lncRNAs and the novel lncRNA WAC-AS1 promotes glycolysis and tumor progression in hepatocellular carcinoma[J].Front Oncol,2021,11(1):1-16.
[10] MA Y,LIU Y,PU Y S,et al.LncRNA IGFL2-AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR-802 in gastric cancer[J].Mol Carcinog,2020,59(3):311-322.
[11] XIE F,XIE G,SUN Q.Long noncoding RNA DLX6-AS1 promotes the progression in cervical cancer by targeting miR-16-5p/ARPP19 axis[J].Cancer Biother Radiopharm,2020,35(2):129-136.
[12] GONG Y,WU W,ZOU X,et al.MiR-26a inhibits thyroid cancer cell proliferation by targeting ARPP19[J].Am J Cancer Res,2018,8(6):1030-1039.
[13] GAO X,LU C,CHEN C,et al.ARPP-19 mediates herceptin resistance via regulation of CD44 in gastric cancer[J].Onco Targets Ther,2020,13(1):6629-6643.
[14] 徐万苏,柯飞,许怡,等.藤梨根提取物通过调控miR-192-5p/ARPP19轴影响结直肠癌细胞的增殖和凋亡[J].世界华人消化杂志,2021,29(8):398-406.
[15] 张春蕾,汤凯悦,杨丽丽,等.肝积方下调ARPP-19表达抑制肝细胞性肝癌肿瘤生长(英文)[J].上海中医药大学学报,2021,35(2):57-67.
[16] JIANG T,ZHAO B,LI X,et al.ARPP-19 promotes proliferation and metastasis of human glioma[J].Neuroreport,2016,27(13):960-966.
[17] MAKELA E,LOYYYTNIEMI E,SALMENNIEMI U,et al.Arpp19 promotes Myc and Cip2a expression and associates with patient relapse in acute myeloid leukemia[J].Cancers(Basel),2019,11(11):1774-1791.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录