血清AFP阳性胃癌中HER2和RRM1的表达及其意义-东南大学学报医学版

血清AFP阳性胃癌中HER2和RRM1的表达及其意义

单位：1. 南京医科大学第一附属医院肿瘤科, 江苏南京 210029;
2. 连云港市第二人民医院肿瘤科, 江苏连云港 222000

分类号：R735.2

出版年·卷·期（页码）：2019·38·第五期（799-805）

摘要：

目的：研究人表皮生长因子2（HER2）和核糖核苷酸还原酶M1（RRM1）在血清AFP阳性胃癌（AFPGC）和普通胃癌之间表达的差异，预测曲妥珠单抗及铂类对AFPGC的疗效。方法：收集AFPGC石蜡标本61例作为实验组，匹配普通胃癌122例作为对照组，以免疫组化法测定HER2和RRM1的表达，比较两组之间表达的差异，并分析其表达与临床病理特征的相关性以及对生存期的影响。结果：HER2在实验组和对照组的阳性表达率分别为45.9%、30.33%，两组的差异有统计学意义（P=0.038）；RRM1的阳性表达率分别为44.26%、62.30%，两组的差异有统计学意义（P=0.02）。在实验组中，HER2在Ⅲ期的阳性表达率明显低于Ⅰ~Ⅱ期（P=0.033），RRM1在分化程度<Ⅲ级的阳性率明显高于Ⅲ级（P=0.008）。在总样本中，HER2阳性胃癌患者的生存期明显比阴性者短，差异有统计学意义（P<0.001）。血清AFP水平（P=0.016，RR=1.001）是AFPGC的独立预后因素。结论：AFPGC的HER2阳性表达率明显高于普通胃癌，RRM1阳性表达率明显低于普通胃癌，提示AFPGC可能对曲妥珠单抗及铂类的治疗有更多的获益。

Objective: To study the differences in the expressions of human epidermal growth factor 2(HER2) and ribonucleotide reductase M1(RRM1) between the serum AFP positive gastric cancer(AFPGC) and the common gastric cancer, in order to predict the effect of trastuzumab and platinum on AFPGC. Methods: Sixty-one cases of AFPGC paraffin specimens were chosen as the experimental group, meanwhile 122 cases of normal gastric cancer were chosen as the control group. The expressions of HER2 and RRM1 were detected by immunohistochemistry. The differences in the expressions of them between the two groups were analyzed, also the correlation between their expressions and clinicopathological characteristics or their influences on the survival time were analyzed. Results: The positive expressions of HER2 in the experimental group and the control group were 45.9% and 30.33%, the difference between the two groups was statistically significant (P=0.038);The positive expressions of RRM1 in the two groups were 44.26% and 62.30%,the difference between the two groups was statistically significant (P=0.02). In the experimental group, the positive expression of HER2 in the stage Ⅲ were significantly lower than that in the stage Ⅰ-Ⅱ (P=0.033),meanwhile the positive expression of RRM1 in the grade that less than Ⅲ were significantly higher than that in the grade Ⅲ (P=0.008). In the total samples, the survival time of the HER2 positive gastric cancer were shorter than that of the HER2 negative gastric cancer,the difference was statistically significant(P<0.001). The serum AFP level (P=0.016,RR=1.001) was the independent prognostic factor of AFPGC. Conclusion: The positive expression of HER2 in AFPGC is significantly higher than that of normal gastric cancer, meanwhile the positive expression of RRM1 in AFPGC is significantly lower than that of normal gastric cancer, suggesting that AFPGC may benefit more from the therapy of trastuzumab and platinum.

参考文献：

[1] HOFMANN M,STOSS O,SHI D,et al.Assessment of a HER2 scoring system for gastric cancer:results from a validation study[J].Histopathology,2008,52(7):797-805.
[2] KONO K,AMEMIYA H,SEKIKAWA T.Clinicopathologic features of gastric cancers producing alpha-fetoprotein[J].Dig Surg,2002,19(5):359-365.
[3] LIU X,CHENG Y,SHENG W,et al.Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers:analysis of 104 cases[J].J Surg Oncol,2010,102(3):249-255.
[4] ARTUFEL M V,VALERO A C,LLADO R R,et al.Molecular protocol for Her2/neu analysis in breast carcinoma[J].Clin Transl Oncol,2005,7(11):504-511.
[5] GRAVALOS C,JIMENO A.HER2 in gastric cancer:a new prognostic factor and a novel therapeutic target[J].Ann Oncol,2008,19(9):1523-1529.
[6] TANNER M,HOLLMRN M,JUNTTILA T T,et al.Amplification of HER2 in gastric carcinoma:association with Topoisomerase Ⅱ alpha gene amplification,intestinal type,poor prognosis and sensitivity to trastuzumab[J].Ann Oncol,2005,16(2):273-278.
[7] BANG Y J,VAN CUTSEM E,FEYEREISLOVA A,et al.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer(ToGA):a phase 3,open-label,randomised controlled trial[J].Lancet,2010,376(9742):687-697.
[8] ROSS J S,McKENNA B J.The HER2/neu oncogenen tumors of the gastrointestinal tract[J].Cancer Invest,2001,19(5):554-568.
[9] WANG S,ZHENG G,XIONG B,et al.Effect of HER2/neu over-expression on prognosis in gastric cancer:a meta-analysis[J].Asian Pacific J Cancer Prev,2011,12(6):1417-1423.
[10] CUELLO M,ETTENBERG S A,CLARK A S,et al.Down-regulation of the erbB-2 receptor by trastuzumab(hemeptin)enhances tumor necrosis factor-related apoptosisinducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2[J].Cancer Res,2001,6(12):4892-4900.
[11] GUITTET O,HAKANSSON P,VOEVODSKAYA N,et al.Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the Rl protein,which is expressed both in resting cells in response to DNA damage and in proliferating cells[J].J Biol Chem,2001,276(44):40647-40651.
[12] ZHENG Z,CHEN T,LI X,et al.DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer[J].N Engl J Med,2007,356(8):800-808.
[13] CAO Y,ZHANG G,WANG P,et al.Clinical significance of UGT1A1 polymorphism and expression of ERCC1,BRCA1,TYMS,RRM1,TUBB3,STMN1 and TOP2A in gastric cancer[J].Am J Transl Res,2016,8(12):5729-5740.
[14] WANG Q,LIU X,ZHOU J,et al.Ribonucleotide reductase large subunit M1 predicts poor survival due to modulation of proliferative and invasive ability of gastric cancer[J].PLoS One,2013,8(7):e70191.
[15] ZHU C M,LIAN X Y,BI Y H,et al.Prognostic value of ribonucleotide reductase subunit M1(RRM1) in non-small cell lung cancer:A meta-analysis[J].Clin Chim Acta,2018,485:67-73.
[16] ALTAHA R,LIANG X,YU J J,et al.Excision repair cross complementing-group 1:gene expression and platinum resistance[J].Int J Mol Med,2004,14(6):959-970.
[17] DUN B,SHARMA A,XU H,et al.Transcriptomic changes induced by mycophenolic acid in gastric cancer cells[J].Am J Transl Res,2013,6(1):28-42.
[18] BEPLER G,KUSMARTSEVA I,SHARMA S,et al.RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer[J].J Clin Oncol,2006,24(29):4731-4737.
[19] 郭迪峰,杨继元,蔡志强,等.下调RRMl基因增强胃癌AGS细胞对奥沙利铂敏感性的实验研究[J].临床肿瘤学杂志,2016,21(2):121-125.

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