子宫内膜癌症状:趋化因子CXCL12及CXCR4在子宫内膜癌安排中mRNA及蛋白表达水平临床研讨

old
中国现代医生
2019年10月14日 02:41

陈晓璐 赵秀敏

[摘要] 意图 通過比照剖析趋化因子CXCL12及CXCR4在子宫内膜癌安排中mRNA及蛋白表达水平,为医治子宫内膜癌供给理论根据。 办法 选取自2014年6月~2017年6月本科室接诊的100例患者为研讨目标。患者年纪为29~77岁,均匀(56.8±9.8)岁。使用安排芯片技能、免疫组化法和RT-PCR法检测患者CXCL12和CXCR4表达水平。调查记载患者的名字、年纪等根本信息,记载患者趋化因子CXCL12及CXCR4表达水对等目标。 效果 CXCL12在子宫内膜癌组患者体内阳性表达率76.8%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者阳性表达率18.8%、50.0%、35.7%,差异有统计学含义(P<0.05);CXCR4在子宫内膜癌组患者体内阳性表达率71.4%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者阳性表达率56.3%、42.9%、28.6%,差异有统计学含义(P<0.05);CXCL12 mRNA在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.587±0.022)、(1.132±0.041),差异有统计学含义(P<0.05);CXCR4 mRAN在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.253±0.035)、(0.522±0.258),差异有统计学含义(P<0.05)。CXCL12表达与患者的肿瘤临床分期、年纪等无关,差异无统计学含义(P>0.05),CXCR4的表达与患者的肿瘤临床分期亲近相关,差异有统计学含义(P<0.05)。 定论 CXCL12及CXCR4在子宫内膜癌患者体内表达水平显着升高,CXCR4表达与患者肿瘤临床分期亲近相关,为子宫内膜癌患者供给精确的医治机遇,一起,为广阔医护人员积累了经历,值得临床广泛推行和使用。

[关键词] CXCL12;CXCR4;子宫内膜癌;mRNA

[中图分类号] R737.33 [文献标识码] A [文章编号] 1673-9701(2018)13-0028-05

Clinical study of mRNA and protein expression level of chemokines CXCL12 and CXCR4 in endometrial carcinoma

CHEN Xiaolu ZHAO Xiumin

Department of Obstetrics and Gynecology, Taizhou First People s Hospital, Taizhou 318020, China

[Abstract] Objective To provide a theoretical basis for the treatment of endometrial cancer by comparing the mRNA and protein expression levels of CXCL12 and CXCR4 in endometrial carcinoma. Methods A total of 100 patients admitted to the department from June 2014 to June 2017 were selected as the study subjects. Patients were at the age of 29-77 years, mean age(56.8±9.8) years. The expression of CXCL12 and CXCR4 was detected by tissue microarray, immunohistochemistry and RT-PCR. Observed and recorded the patients name, age and other basic information, recorded patient treatment efficacy. Results The positive expression rate of CXCL12 in endometrium group was 76.8%, which was significantly higher than that in atypical endometrial hyperplasia group, simple endometrial hyperplasia group and normal endometrium group whose positive expression rates of CXCL12 were 18.8%, 50.0%, 35.7% respectively, the differences were statistically significant(P<0.05). The positive expression rate of CXCR4 in endometrium group was 71.4%, which was significantly higher than that in atypical endometrial hyperplasia group, simple endometrial hyperplasia group and normal endometrium group whose positive expression rates of CXCR4 were 56.3%、42.9%、28.6% respectively, the differences were statistically significant(P<0.05). The expression levels of CXCL12 mRNA were (0.587±0.022) and (1.132±0.041) in the normal endometrium group and the endometrial carcinoma group respectively(P<0.05). The expression levels of CXCR4 mRNA were (0.253±0.035) and (0.522±0.258) in the normal endometrium group and endometrial cancer group respectively, and the difference was statistically significant(P<0.05). The expression of CXCL12 was not related to the clinical stage and age of the tumor, and the difference was not statistically significant(P>0.05). The expression of CXCR4 was closely related to the clinical stage of tumor, and the difference was statistically significant(P<0.05). Conclusion The expression of CXCL12 and CXCR4 in patients with endometrial carcinoma was significantly increased. The expression of CXCR4 was closely related to the clinical stage of the tumor which provided accurate timing for the treatment of patients with endometrial cancer. At the same time, the majority of medical staff accumulated abundant experience from and these indicators can be widely applied.

[Key words] CXCL12; CXCR4; Endometrial cancer; mRNA

子宫内膜癌是一种发生于女人子宫内膜上皮、严峻影响女人身体健康的恶性肿瘤,发病率居各种女人常发恶性肿瘤第6位,死亡率居女人常发各种恶性肿瘤第5位[1]。近年来,跟着人们寿数的延伸和外源性雌激素的很多使用,子宫内膜癌在全世界范围内的发病率逐渐进步,尤其是欧美国家,其发病率已达女人恶性肿瘤的第一位,给广阔的女人带来严峻损伤[2]。子宫内膜癌发病藏匿,一般患者发现时均处于胃癌晚期,给医治带来极大困难。趋化因子是细胞因子宗族中的一员,CXCL12是一种参加神经元细胞构成、B淋巴细胞生成、心血管内皮细胞的开展和骨髓髓系细胞生成的趋化因子[3]。CXCR4是CXCL12的特异性受体,主要在中枢神经细胞、血液和免疫细胞表达。趋化因子CXCL12和它的受体CXCR4构成的CXCL12/CXCR4生物学轴在肿瘤细胞的侵袭、搬运、分解等方面有着重要的效果[4]。现在,国内外的医学工作者投入很多精力和时刻来研讨子宫内膜癌的确诊、医治及预后,尽管获得必定的效果,可是预后效果依然距人们要求有较大距离,5年生存率仅为17%左右[5]。为更深化剖析了解趋化因子CXCL12及CXCR4在子宫内膜癌安排中mRNA及蛋白表达水平,本次采纳操控单一变量办法进行研讨剖析,为确诊医治子宫内膜癌供给新的根据,现将效果报导如下。

1 目标与办法

1.1研讨目标

选取自2014年6月~2017年6月本科室接诊的100例患者为研讨目标,其间确诊为子宫内膜癌并在本科室施行医治的患者56例,单纯性内膜增生患者14例,不典型内膜增生患者16例,正常内膜14例。患者年纪29~77岁,均匀(56.8±9.8)岁。<50岁的35例,≥50岁的65例。各组患者的年纪、身高、体重和病程等临床材料比较差异无统计学含义(P>0.05),具有可比性,见表1。

1.2 归入、扫除规范

归入规范:确诊为子宫内膜癌患者;未患有影响本次研讨的其他疾病;入院之前未进行放疗、化疗、激素等医治;赞同参加本次研讨。

扫除规范:患者确诊、医治等病历材料不全者;手术之前经评价肿瘤无法完好切除的患者;无法参加研讨者;半途退出研讨者[6]。

1.3研讨办法

使用安排芯片技能和免疫组化法检测正常内膜、子宫内膜癌、单纯性内膜增生和不典型内膜增生四组患者CXCL12和CXCR4表达水平,使用RT-PCR法检测子宫内膜癌和正常内膜患者CXCL12和CXCR4 mRNA表达水平。制造的芯片均由具有10年以上阅片经历的医生阅片。当患者细胞膜内或细胞质内呈现棕黄色上色颗粒,即为CXCL12和CXCR4阳性表达。

1.4 调查目标

调查记载患者的名字、年纪、身高、体重、病程、肿瘤部位等根本信息,亲近调查患者的病况改变,记载患者手术过程中呈现的不良反应、手术时刻等状况,及时监测患者生化目标,记载患者CXCL12和CXCR4等目标。

1.5统计学办法

选用SPSS 21.0软件对数据材料进行统计学剖析。计数材料选用χ2查验,计量材料选用t查验,P<0.05为差异有统计学含义。

2 效果

2.1 CXCL12在各组患者中的表达状况

CXCL12在子宫内膜癌组患者体内阳性表达率为76.8%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者的阳性表达率18.8%、50.0%和35.7%,差异有统计学含义(P<0.05),不典型内膜增生组CXCL12阳性表达率低于正常内膜组患者阳性表达率,差异有统计学含义(P<0.05),单纯性内膜增生组CXCL12阳性表达率与不典型内膜增生组、正常内膜组患者阳性表达率差异无统计学含义(P>0.05),见表2。

2.2 CXCR4在各组患者中的表达状况

CXCR4在子宫内膜组患者体内阳性表达率71.4%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者阳性表达率56.3%、42.9%、28.6%,差异有统计学含义(P<0.05),不典型内膜增生组患者的CXCR4阳性表达率与正常内膜组者阳性表达率差异无统计学含义(P>0.05),见表3。

2.3 CXCL12在子宫内膜癌组患者中的表达状况及与患者病理联系的剖析

CXCL12表达状况与患者肿瘤临床分期、年纪等病理状况无关,差异无统计学含义(P>0.05),见表4。

2.4 CXCR4在子宫内膜癌组患者中的表达状况及与患者病理联系的剖析

CXCR4表达状况与患者肿瘤临床分期亲近相关,差异有统計学含义(P<0.05),见表5。

2.5 CXCL12 mRNA表达状况剖析

CXCL12 mRNA在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.587±0.022)、(1.132±0.041),差异有统计学含义(P<0.05),见表6。

2.6 CXCR4 mRNA表达状况剖析

CXCR4 mRNA在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.253±0.035)、(0.522±0.258),差异有统计学含义(P<0.05),见表7。

表7 CXCR4 mRNA表达状况剖析(x±s)

3评论

近年来,我国癌症发病人数及发病速度均在不断增多和加速[7-8]。癌症已经成为严峻影响和限制我国公民身体素质开展的重要因素。影响癌症开展的主要有肿瘤细胞分解程度、肿瘤细胞滋润深度、淋巴结搬运程度等[9-11]。及早发现,及早医治,是能有用医治和操控癌症的最为有用的办法[12-14]。可是,一般状况下,癌症患者发现患病即为癌症中晚期,给医治带来极大困难。尤其是子宫内膜癌,前期发现较难,患者一般在偶尔查看中发现,给患者及家族带来巨大的精力压力和经济负担[15-17]。能赶快并且很方便地确诊癌症已是广阔医护人员和患者的最大呼声。近几年,很多的医护人员经过检测CXCL12及CXCR4在子宫内膜癌安排中mRNA及蛋白表达水平来确诊剖析子宫内膜癌及研讨癌细胞的搬迁改变[18]。CXCR4和CXCL12之间具有高度的特异性和亲和力,在肿瘤细胞搬运中发挥着重要的效果[19-20]。跟着科学技能和医学水平的开展和进步,人们对癌症的知道正在逐渐加深。现在,国内外的很多医护人员和科研机构依然在对子宫内膜癌的确诊、开展、医治和预后进行研讨,力求提前有突破性的开展,为广阔患者带来福音。跟着人们研讨的深化和注重程度的加深,人们必将找到一种科学的安全的确诊医治办法,为子宫内膜癌患者及其家族减轻精力压力和经济负担。

本次研讨标明,患者的身高、体重、年纪、病程等散布差异无统计学含义,对子宫内膜癌细胞的分解、搬迁等影响不显着。CXCL12在子宫内膜癌组患者体内阳性表达率76.8%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者阳性表达率18.8%、50.0%、35.7%,不典型内膜增生组CXCL12阳性表达率低于正常内膜组患者阳性表达率16.9个百分点,单纯性内膜增生组CXCL12阳性表达率与正常内膜组患者阳性表达率无显着差异。CXCL12与CXCR4构成的生物学轴,对细胞的迁徙、滋润以及器官发育有严重影响。CXCR4在子宫内膜癌组患者体内阳性表达率71.4%,显着高于不典型内膜增生组、单纯性内膜增生组和正常内膜组患者阳性表达率56.3%、42.9%、28.6%,不典型内膜增生组患者CXCR4阳性表达率与正常内膜组者阳性表达率无显着差异,经过确诊检测CXCL12与CXCR4的含量水平,能有用的确诊患者子宫内膜癌病况开展状况。CXCL12表达状况与患者肿瘤临床分期、年纪等病理状况无关,CXCR4表达,与患者肿瘤临床分期亲近相关,肿瘤分期越深,其肿瘤细胞搬运越多、越快,其CXCL12与CXCR4水平会有显着动摇,会对肿瘤病况有较显着的预示效果。CXCL12 mRNA在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.587±0.022)、(1.132±0.041),具有显着差异,跟着子宫内膜癌症的开展,患者体内CXCL12 mRNA水平显着升高,肿瘤细胞经过人体机体效果,影响患者细胞,致使 CXCL12 mRNA高表达,这也是确诊肿瘤病况的重要标志。CXCR4 mRNA在正常内膜组和子宫内膜癌组患者体内表达水平分别为(0.253±0.035)、(0.522±0.258),具有显着差异,与国内部分专家的研讨效果根本共同[21]。

综上所述,CXCL12及CXCR4在子宫内膜癌患者体内表达水平显着升高,CXCR4表达与患者肿瘤临床分期亲近相关,在必定程度上能精确反映患者肿瘤状况及预后,为子宫内膜癌患者供给精确的医治机遇,给患者及家族减轻精力和经济负担,一起为广阔医护人员积累了经历,值得广泛推行和使用。

[參考文献]

[1] Wang X,Mamillapalli R,Mutlu L,et al. Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression[J]. Stem Cell Research,2015,15(1):14-22.

[2] 马营营,黄煜,颜莉莉,等.ERK信号转导通路在CXCL12促进子宫内膜癌细胞增殖和侵袭中的效果[J]. 我国肿瘤生物医治杂志,2016,23(2):250-254.

[3] Oguejiofor CF,Cheng Z,Abudureyimu A,et al. Global transcriptomic profiling of bovine endometrial immune response in vitro. II. Effect of bovine viral diarrhea virus on the endometrial response to lipopolysaccharide[J]. Biology of Reproduction,2015,93(4):101.

[4] 吴唯,钱立元,戴荆,等.乳腺癌安排中趋化因子CXCL12及其受体CXCR4、CXCR7的表达及临床含义[J]. 我国普通外科杂志,2015,24(11):1577-1582.

[5] 史芳涛,王庆锋.凋亡按捺蛋白基因Livin及肿瘤搬运相关基因在肺癌安排中的表达及其与肺癌临床特征的联系剖析[J].癌症开展,2017,15(7):794-797.

[6] Li Z,Wang W,Xu H,et al. Effects of altered CXCL12/CXCR4 axis on BMP2/Smad/Runx2/Osterix axis and osteogenic gene expressions during osteogenic differentiation of MSCs[J].American Journal of Translational Research,2017,9(4):1680.

[7] Bi Y,Li J,Ji B,et al. Sphingosine-1-phosphate mediates a reciprocal signaling pathway between stellate cells and cancer cells that promotes pancreatic cancer growth. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer[J].Bmc Cell Biology,2015,13(1):1-12.

[8] 张钰,王建梅,顾艳,等.调理趋化因子CXCL12、CCL2、RANTES及其受体表达对天然流产模型小鼠妊娠结局的影响[J].我国妇幼保健,2015,30(15):2407-2411.

[9] Cutolo P,Basdevant N,Bernadat G,et al. Interaction of chemokine receptor CXCR4 in monomeric and dimeric state with its endogenous ligand CXCL12:Coarse-grained simulations identify differences[J]. Journal of Biomolecular Structure & Dynamics,2017,35(2):399-412.

[10] 李建,杜翠琴,赵卫东. CXCL12,CXCR4及CXCR7表达检测对乳腺癌患者疾病预后含义讨论[J]. 癌症开展,2016,14(12):1225-1229.

[11] Quinn KE, Prosser SZ, Kane KK, et al. Inhibition of chemokine(C-X-C motif) receptor four (CXCR4) at the fetal-maternal interface during early gestation in sheep:alterations in expression of chemokines, angiogenic factors and their receptors[J].Journal of Animal Science,2017,95(3):1144.

[12] 杜亚奇,刘东屏,孙明军,等.不同等级胃黏膜上皮瘤变安排幽门螺杆菌感染和趋化因子CXCL12及受体CXCR4表达的联系及含义[J]. 我国医生进修杂志,2015, 38(9):635-639.

[13] 于转转,郗彦凤,李静,等.CXCL12/CXCR4与 T 淋巴母细胞淋巴瘤/白血病预后的相关性[J].中华病理学杂志,2016,45(12):838-843.

[14] Weiss ID,Huff L M,Evbuomwan MO,et al.Screening of cancer tissue arrays identifies CXCR4 on adrenocortical carcinoma:correlates with expression and quantification on metastases using64Cu-plerixafor PET[J]. Oncotarget,2017,8(43):73387-73406.

[15] 郭春艷,韩波,梁皓,等. CXCL12/CXCR4生物轴对缓慢病毒性心肌炎小鼠心肌纤维化的影响[J].山东医药,2017,57(17):21-24.

[16] Hu S C,Yu H,Yen F,et al. CXCR7 expression correlates with tumor depth in cutaneous squamous cell carcinoma skin lesions and promotes tumor cell survival through ERK activation[J]. Experimental Dermatology, 2015, 23(12):902-908.

[17] 金笛,何丽,张海锋.内质网应激相关蛋白与CXCL12蛋白在特发性肺纤维化中的表达及含义[J]. 重庆医学,2016,45(29):4068-4070.

[18] Li S,Tian H,Yue W,et al. Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas,based on the 2011 IASLC/ATS/ERS classification[J]. Oncology Letters,2016,11(1):224.

[19] 石锋,郭苹.CXCL12/CXCR4自排泄环对人非小细胞肺癌细胞株A549搬运潜能的影响[J].广东医学, 2016, 37(10):1442-1446.

[20] Fernando R,Atkins SJ,Smith TJ. Intersection of Chemokine and TSH Receptor Pathways in Human Fibrocytes:Emergence of CXCL-12/CXCR4 Cross Talk Potentially Relevant to Thyroid-Associated Ophthalmopathy[J]. Endocrinology,2016,157(10):3779.

[21] 汪伟,宁宇,许海甲,等.重组腺病毒CXCL12基因表达载体的构建及其转染间充质干细胞后对其Runx2基因表达的影响[J]. 生物技能通讯,2016,27(4):463-467.

(收稿日期:2018-01-13)

健康之友©部分网站内容来自网络,如有侵权请联系我们,立即删除!
患者 水平 内膜
你该读读这些:一周精选导览
更多内容...

TOP

More