董曉剛 皮芹 安外爾約 .麥爾阿卜拉 郭文佳
[摘要] 目的 探討Survivin和Egr-1在食管鱗癌組織和正常食管組織中的表達(dá)情況,分析Survivin和Egr-1與食管鱗癌臨床病理特征和預(yù)后的相關(guān)性。方法 采用免疫組織化學(xué)染色方法檢測(cè)2012年1月—2014年6月方便收集的80例食管鱗癌組織和20例正常食管組織中Survivin和Egr-1的蛋白表達(dá)水平,統(tǒng)計(jì)分析Survivin和Egr-1與臨床病理特征和生存預(yù)后之間的關(guān)系。結(jié)果 Survivin在食管鱗癌組織中陽(yáng)性表達(dá)率為68.8%(55/80),高于在正常組織中的陽(yáng)性表達(dá)率5.0%(1/20)(χ2=26.39,P<0.05)。Egr-1在食管鱗癌中的低表達(dá)率為66.3%(53/80),高于正常組織中的15.0%(3/20)(χ2=17.06,P<0.05)。Survivin蛋白在食管鱗癌中陽(yáng)性高表達(dá)與患者的性別、年齡以及腫瘤的分化程度,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),與食管鱗癌患者TNM分期、腫瘤的浸潤(rùn)深度、腫瘤大小以及淋巴結(jié)是否轉(zhuǎn)移,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。Egr-1蛋白在食管鱗癌中陽(yáng)性低表達(dá)與患者性別、腫瘤大小以及腫瘤浸潤(rùn)深度,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),與食管鱗癌患者年齡、TNM分期、腫瘤分化程度以及淋巴結(jié)是否轉(zhuǎn)移,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。隨訪結(jié)果顯示食管鱗癌患者5年生存率為48.9%,中位生存時(shí)間為53.1個(gè)月。結(jié)論 Survivin和Egr-1在食管鱗癌的發(fā)生發(fā)展中起重要作用,聯(lián)合檢測(cè)兩者對(duì)判斷食管鱗癌的預(yù)后有一定的指導(dǎo)意義,Survivin和Egr-1有望作為食管鱗癌的治療或者預(yù)后預(yù)測(cè)靶標(biāo)。
[關(guān)鍵詞] Survivin;Egr-1;食管鱗癌;免疫組化
[Abstract] Objective To investigate the expression of Survivin and Egr-1 in esophageal squamous cell carcinoma tissues and normal esophageal tissues, and to analyze the correlation between Survivin and Egr-1 and the clinicopathological characteristics and prognosis of esophageal squamous cell carcinoma. Methods The expression levels of Survivin and Egr-1 in 80 esophageal squamous cell carcinoma tissues and 20 normal esophageal tissues conveniently collected from January 2012 to June 2014 were detected by immunohistochemical staining. Survivin and Egr-1 were statistically analyzed. Relationship with clinicopathological characteristics and survival prognosis. Results The positive expression rate of Survivin in esophageal squamous cell carcinoma was 68.8% (55/80), which was higher than that in normal tissues 5.0%/(1/20)(χ2=26.39, P<0.05). The low expression rate of Egr-1 in esophageal squamous cell carcinoma was 66.3% (53/80), which was higher than 15.0% (3/20) in normal tissues(χ2=17.06, P<0.05). The positive expression of Survivin protein in esophageal squamous cell carcinoma was not significantly different from the patient's gender, age, and tumor differentiation(P>0.05). It was different from TNM staging, tumor invasion depth, tumor size, and lymph nodes in patients with esophageal squamous cell carcinoma. The difference was statistically significant(P<0.05). There was no statistically significant difference between the positive expression of Egr-1 protein in esophageal squamous cell carcinoma and the patient's gender, tumor size, and depth of tumor invasion(P>0.05). It was different from the age, TNM stage, tumor differentiation, and lymph nodes of patients with esophageal squamous cell carcinoma. The difference was statistically significant(P<0.05). The follow-up results showed that the 5-year survival rate of patients with esophageal squamous cell carcinoma was 48.9%, and the median survival time was 53.1 months. Conclusion Survivin and Egr-1 play an important role in the occurrence and development of esophageal squamous cell carcinoma. The combined detection of both has certain guiding significance for judging the prognosis of esophageal squamous cell carcinoma. Survivin and egr-1 are expected to be therapeutic or prognostic targets for esophageal squamous cell carcinoma.
Survivin和Egr-1與腫瘤的關(guān)系較為復(fù)雜,二者與癌基因和抑癌基因的關(guān)系、對(duì)ESCC中靶基因調(diào)節(jié)的分子機(jī)制等尚未研究清楚,國(guó)內(nèi)外對(duì)二者與放射誘導(dǎo)后相關(guān)基因表達(dá)變化以及對(duì)放射敏感性的影響研究也較少,對(duì)這些問題的不斷深入研究和解決將有助于對(duì)ESCC個(gè)體化診治起到基礎(chǔ)理論作用。該研究運(yùn)用免疫組化的方法聯(lián)合檢測(cè)ESCC中Survivin和Egr-1的表達(dá)情況,后期還可以嘗試聯(lián)合檢測(cè)Survivin和Egr-1蛋白在ESCC患者血清中與組織中的表達(dá),考察其是否可以成為ESCC新的腫瘤標(biāo)記物,為ESCC的早期診斷提供新的方法。
[參考文獻(xiàn)]
[1]? 喬友林.食管癌流行病學(xué)研究的重要里程碑[J].中國(guó)腫瘤臨床,2016,43(12):500-501.
[2]? Allemani C,Matsuda T,Di Carlo V,et al.Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37?513?025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J].Lancet,2018,391(10125):1023-1075.
[3]? 陳萬(wàn)青,鄭榮壽,張思維,等.2013年中國(guó)惡性腫瘤發(fā)病和死亡分析[J].中國(guó)腫瘤,2017,26(1):1-7.
[4]? 王云,李運(yùn)紅.胃癌中survivin的研究進(jìn)展[J].中國(guó)臨床研究,2017,30(4):546-548.
[5]? Mikami D,Kobayashi M,Uwada J,et al.β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cells[J].J Pharmacol Sci,2019,142(1):1-8.
[6]? Bianco B,F(xiàn)ilipchiuk C,Christofolini DM,et al.The role of survivin in the pathogenesis of endometriosis[J].Minerva Med,2020,11(1):21-32.
[7]? Nitschkowski D,Marwitz S,Kotanidou SA,et al.Live and let die: epigenetic modifications of Survivin and Regucalcin in non-small cell lung cancer tissues contribute to malignancy[J].Clin Epigenetics,2019 ,11(1):157.
[8]? Wang L,En H,Yang L,et al.miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib[J].Onco Targets Ther,2019,12:6825-6838.
[9]? Sabour R,Harras MF,Mehany ABM.Design,synthesis,cytotoxicity screening and molecular docking of new 3-cyanopyridines as survivin inhibitors and apoptosis inducers[J].Bioorg Chem,2019,11:103358.
[10]? 楊嬌嬌,金阿榮.凋亡抑制蛋白survivin在惡性腫瘤中的研究進(jìn)展[J].內(nèi)蒙古醫(yī)學(xué)雜志,2017,49(6):679-682.
[11]? 馬旸,崔東倩,韓陳陳,等.IGF-1通過(guò)激活EGR1誘導(dǎo)肝細(xì)胞癌的遷移和侵襲[J].安徽醫(yī)科大學(xué)學(xué)報(bào),2019,54(11): 1750-1755.
[12]? 李雅琴,史龍泉,王宏?yáng)|,等.Egr-1和PTEN在皮膚鱗癌中的表達(dá)和臨床意義[J].現(xiàn)代生物醫(yī)學(xué)進(jìn)展,2018,18(12):2333,2343-2346.
[13]? 卡吾力·居買,居來(lái)提·艾尼瓦爾,張海,等.食管癌精準(zhǔn)治療靶點(diǎn)篩查研究現(xiàn)狀與展望[J].新鄉(xiāng)醫(yī)學(xué)院學(xué)報(bào),2018,35(9):827-834,839.
[14]? 高會(huì)江,尚曉濱,于振濤,等.食管癌免疫檢查點(diǎn)抑制劑的研究進(jìn)展[J].中華外科雜志,2019,57(10): 795-800.
[15]? 鄭顏偉,劉虹妤,金曉明.凋亡抑制蛋白Survivin在腫瘤免疫治療中的前景[J].國(guó)際免疫學(xué)雜志,2019,42(4): 418-421.
[16]? 李炎,郭華榮.Survivin基因的研究進(jìn)展[J].海洋科學(xué)前沿,2019,6(2):41-45.
[17]? Zheng ZH,Wu DM,F(xiàn)an SH,et al.LncRNA AB209371 up-regulated Survivin gene by down-regulating miR-203 in ovarian carcinoma[J].J Ovarian Res,2019,12(1):92.
[18]? 牛朝霞,張秀芝,陳潔,等.Survivin基因沉默抑制食管癌Eca-109細(xì)胞的侵襲與遷移[J].安徽醫(yī)科大學(xué)學(xué)報(bào),2016,5(21):185-187.
[19]? Ting Lei,Xiaodong Zhu,Kai Zhu.EGR1-induced upregulation of lncRNA FOXD2-AS1 promotes the progression of hepatocellular carcinoma via epigenetically silencing DKK1 and activating Wnt/β-catenin signaling pathway[J].Cancer Biology & Therapy,2019,20(7):1007-1016.
[20]? Jie Shen,Wanhong Xing,F(xiàn)angqi Gong.MiR-150-5p retards the progression of myocardial fibrosis by targeting EGR1[J].Cell Cycle,2019,18(12):1335-1348.
[21]? 丁家寶,王亞軒,李景東,等.E2F1及EGR-1在腎透明細(xì)胞癌中的表達(dá)及意義[J].河北醫(yī)藥,2015 (20): 3045-3048.
[22]? 柯燦燦,繆振忠,王芬.聯(lián)合檢測(cè)EGR-1與HER-2在卵巢癌中的表達(dá)及意義[J].江西醫(yī)藥,2018,53(11):1219-1223.
[23]? 李洪佳,董廣璐.Egr-1基因與腫瘤及放射治療研究進(jìn)展[J].中華腫瘤防治雜志,2012,19(22):1753-1756.
[24]? 劉敏姬,沈守榮.結(jié)直腸癌中Egr-1的表達(dá)及意義[J].數(shù)理醫(yī)藥學(xué)雜志,2016,29(1):1-2.
[25]? 李雅琴,史龍泉,王宏?yáng)|,等.Egr-1 和 PTEN 在皮膚鱗癌中的表達(dá)和臨床意義[J].現(xiàn)代生物醫(yī)學(xué)進(jìn)展,2018,18(12):2343-2346.
(收稿日期:2020-02-26)