原发性肝癌组织CCR7、MCM10蛋白与临床病理特征及预后的相关性

目的 探讨原发性肝癌(PHC)组织趋化因子受体7(CCR7)、微染色体维持蛋白10(MCM10)与临床病理特征及预后的相关性。方法 选取2017年1月至2020年12月周口市中心医院90例PHC患者为研究对象,均行肝癌切除术,术中取肿瘤组织及癌旁正常组织。比较PHC不同组织CCR7、MCM10蛋白表达,χ^(2)检验分析CCR7、MCM10表达与临床病理特征的关系,Kaplan-Meier分析CCR7、MCM10蛋白表达与PHC患者预后的关系,Cox回归分析PHC患者预后影响因素,Kaplan-Meier分析CCR7、MCM10蛋白表达亚组与PHC患者预后的关系。结果 PHC患者肿瘤组织中CCR7、MCM10蛋白阳性表达分别为66.67%、75.56%,高于正常组织的23.33%、27.78%,差异有统计学意义(P<0.05);有淋巴结转移、血管侵犯患者癌组织中CCR7、MCM10蛋白阳性表达率(79.25%、94.34%,81.58%、89.47%)高于无淋巴结转移、血管侵犯患者(48.65%、48.65%,55.77%、65.38%),差异有统计学意义(P<0.05);Kaplan-Meier生存分析显示,CCR7、MCM10蛋白阳性表达患者的3 a生存率分别为39.66%(23/58)、41.54%(27/65),低于阴性表达患者的68.97%(20/29)、72.73%(16/22),差异有统计学意义(P<0.05);Cox回归分析显示,淋巴结转移(95%CI:1.129~3.025)、血管侵犯(95%CI:1.463~3.147)、CCR7蛋白(95%CI:1.407~3.524)、MCM10蛋白(95%CI:1.384~3.441)均为PHC患者预后的独立危险因素(P<0.05);Kaplan-Meier分析显示,CCR7蛋白阳性+MCM10蛋白阳性亚组预后最差,CCR7蛋白阴性+MCM10蛋白阴性亚组预后最好,各亚组间比较差异均有统计学意义(P<0.05)。结论 PHC组织CCR7、MCM10蛋白表达与临床病理特征及预后相关,二者均阳性表达是预后不良的危险因素,可作为临床评估病情、预测预后的辅助指标,并对临床防治具有一定指导意义。

哮喘大鼠树突状细胞CCR7对共刺激分子CD80、CD86表达的影响研究

目的 通过观察哮喘大鼠树突状细胞CCR7对共刺激分子CD80、CD86表达的影响,研究其在免疫耐受中的作用。方法 建立哮喘大鼠模型,提取骨髓来源的树突状细胞,将编码过表达CCR7基因的重组腺病毒及有靶向CCR7基因的短发夹RNA腺病毒载体转染树突状细胞(DC)。同时培养脾脏来源T淋巴细胞,与转染后的DC行混合淋巴细胞反应,采用MTT比色法测定淋巴细胞增殖能力;采用蛋白质免疫印迹试验检测DC中CCR7的蛋白表达水平;流式细胞仪检测DC表面CD80、CD86表达;酶联免疫吸附法检测IL-10、IL-12、TGF-β表达水平。结果 CCR7基因过表达组CCR7蛋白表达水平增高,CD80、CD86表达水平较哮喘组明显升高,CCR7基因敲低组二者的表达水平较哮喘组降低(P<0.001);IL-12在CCR7基因敲低组较哮喘组明显升高;CCR7基因过表达组IL-10及TGF-β表达水平较敲低组升高,CCR7基因敲低组TGF-β蛋白表达水平较哮喘组明显降低(P<0.001)。结论 共刺激分子的激活可能通过DC表面CCR7表达的介导来实现。同时,CCR7可影响IL-10、IL-12和TGF-β的蛋白表达水平来诱导哮喘免疫耐受。

Expression pattern of mda-7/IL-24 receptors in liver cancer cell lines

BACKGROUND: The mda-7/IL-24 receptor belongs to the type 11 cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy. METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were amplified by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed. RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1; BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor. CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.

Role of P2X_7 receptors in the development of diabetic retinopathy

The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.

Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson’s disease

To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson’s disease.It was recently observed in a rodent model of Alzheimer’s disease that the interaction between the α7 subtype of nicotinic acetylcholine receptor(α7-nAChR)and sigma-1 receptor(σ1-R)could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson’s disease.In this context,the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide(PHA)543613 as an α7-nAChR agonist and 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate(PRE)-084 as aσ1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson’s disease.The animals received either vehicle separately or the dual therapy PHA/PRE once a day until day 14 postlesion.Although no effect was noticed in the amphetamine-induced rotation test,our data has shown that the PHA/PRE treatment induced partial protection of the dopaminergic neurons(15-20%),assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia nigra.Furthermore,this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion,i.e,the 18 kDa translocation protein density and glial fibrillary acidic protein staining in the striatum,and the CD11b and glial fibrillary acidic protein staining in the substantia nigra.Hence,this study reports for the first time that concomitant activation of α7-nAChR andσ1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial activation.The study was approved by the Regional Ethics Committee(CEEA Val de Loire n°19)validated this protocol(Authorization N°00434.02)on May 15,2014.

Role of P2X_7 receptors in neuronal death in the retina

Acknowledgments： I would like to express my appreciation to Professor Puro DG for leading me to this research topic during my stay as a research fellow in his laboratory at the University of Michigan in 2001, and also to Professor Ikeda T forgiving me the opportunity to study abroad and then to continue to investigate this topic in the Department of Ophthalmology at Osaka Medical College, lapan.

CXCL12 Retargeting of an Oncolytic Adenovirus Vector to the Chemokine CXCR4 and CXCR7 Receptors in Breast Cancer

Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant progress has been made in developing targeted therapies for breast cancer, advanced breast cancer continues to have high mortality, with poor 5-year survival rates. Thus, current therapies are insufficient in treating advanced stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We showed that the modified virus targets and infects CXCR4- and CXCR7-overexpressing breast cancer cells more efficiently than a wild-type control vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.

趋化因子受体CCR7在不同类型肺癌组织中的表达

目的探讨趋化因子受体CCR7在不同类型肺癌组织中的表达。方法选取2019年6月-2023年6月在本院就诊的59例NSCLC患者作为研究对象,采用免疫组化方法检测不同地区及不同病理类型肺癌组织中CCR7的表达。SPSS 17.0统计软件进行数据分析。结果免疫组化:肺癌组织中CCR7的表达明显高于正常肺组织;不同地区及病理类型肺癌组织中均表达CCR7,其中宣威及个旧地区肺癌组织中CCR7的表达较其他地区肺癌明显升高,差异有统计学意义(P<0.05);宣威地区与个旧地区肺癌组织中CCR7的表达无明显差异;CCR7的表达与淋巴结转移有关,CCR7的表达与肺癌病理类型无关。结论CCR7在肺癌组织中是高表达,CCR7的表达存在地域差异,其表达与淋巴结转移有关,与肺癌病理类型无关。

激活巨噬细胞Toll样受体7对肺动脉高压中肺动脉平滑肌增殖与迁移的影响

目的探索激活巨噬细胞的Toll样受体7(TLR7)对肺动脉高压(PH)大鼠肺动脉平滑肌(PASMC)增殖与迁移的影响及其机制。方法动物实验:12只雄性标准体重大鼠适应性喂养1周后,使用随机数字表法均分为两组,PH组腹腔注射野百合碱60 mg/kg,对照组腹腔注射生理盐水60 mg/kg,4周后取肺组织行免疫荧光染色。细胞实验:取健康雄性标准体重大鼠的原代PASMC,其单独培养为PASMC组,与RAW264.7细胞共培养为co-culture组,与激活TLR7的RAW264.7细胞共培养为R848+co-culture组。α-SMA免疫荧光染色鉴定PASMC;PASMC或RAW264.7细胞各分为四组,分别用0、0.1、1.0、10.0μg/ml的R848处理24 h或48 h,采用CCK8法检测细胞增殖;划痕实验检测迁移;Western blot法检测增殖细胞核抗原(PCNA)、Ki67表达;PCR检测CD68、CD86、CD206、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-10转录情况。结果大鼠免疫荧光染色显示,PH大鼠肺血管周围TLR7+巨噬细胞增多。CCK8与迁移实验提示,co-culture组与R848+co-culture组细胞增殖活性与迁移能力均高于PASMC组(P<0.05),R848+co-culture组高于co-culture组(P<0.01)。Western blot法与PCR法检测结果显示,co-culture组与R848+co-culture组PASMC中PCNA及Ki67 mRNA及蛋白表达均高于PASMC组(P<0.05),R848+co-culture组高于co-culture组(P<0.01)。PCR结果提示,0.1μg/ml R848处理巨噬细胞,代表M1表型的CD86、促炎性细胞因子TNF-α及IL-6转录水平高于0μg/ml R848处理巨噬细胞,抑炎性细胞因子IL-10转录低于0μg/ml R848处理巨噬细胞(P<0.05)。结论在PH病理机制中,激活巨噬细胞TLR7可促进PASMC的增殖与迁移,其潜在机制可能与巨噬细胞向M1型分化及促炎性细胞因子TNF-α、IL-6转录增多有关。

Expression of BMP-7 and its receptors in renal tubolo-interstitial fibrosis induced with unilateral ureteral obstruction in rats

Objective:To study the changes of the expression of bone morphogenetic protein-7(BMP-7) and its receptors(BMPR-Ⅱ,ALK2,ALK3 and ALK6) in the renal tubulointerstitial fibrosis induced with unilateral ureteral obstruction in rats. Methods: Sixty Wistar male rats were divided randomly into the normal control,sham-operation and unilateral ureteral obstruction(UUO) groups and the rats were killed on the 1st,3rd,7th and 14th postoperative days respectively.The mRNA level of BMP-7,BMPR-Ⅱ,ALK2,ALK3 and ALK6 was determined with RT-PCR.The site and level of protein expression of BMP-7 were observed with immunohistochemical staining. Results: The mRNA level of BMP-7,BMPR-Ⅱ,ALK2 and ALK3 was significantly decreased in the rats of UUO group than in those of the sham-operation group but the mRNA level of ALK6 showed no obvious changes in all the rats.Immunohistochemical staining revealed that the protein of BMP-7 was mainly expressed in the renal tubules and interstitial tissue of the kidneys in normal rats but it was decreased gradually along with the unilateral ureteral obstruction. Conclusion: It is found that the loss of BMP-7 and its receptors including BMPR-Ⅱ,ALK2 and ALK3 occurs in the early phase of renal tubulointerstitial fibrosis before the appearance of other pathological changes in the kidney and may play an important role in the occurrence and progress of renal tubulointerstitial fibrosis.

大肠癌中CCR7、L-selectin、CD44v6和MMP9表达及其与淋巴转移的关系

目的探讨CC趋化因子受体7(CCR7)、L-selectin、CD44v6和MMP9在大肠癌组织中的表达及其与大肠癌淋巴转移的关系。方法采用免疫组化PV 9000两步法检测104例大肠癌组织(大肠癌组)、55例癌旁正常组织(癌旁组)和34例转移灶组织(转移组)中CCR7和L-selectin、CD44v6和MMP9的表达。结果大肠癌组、转移组中CCR7、L-selectin、CD44v6和MMP9阳性率明显高于癌旁组(P<0.05),有淋巴结转移者明显高于无转移者(P<0.05);CCR7与L-selectin、MMP9表达呈正相关(P<0.05);CD44v6与L-selectin、MMP9表达相关;L-selectin与MMP9的表达呈正相关。结论 CCR7、L-selectin、CD44v6和MMP9在大肠癌中的表达与大肠癌的发生、淋巴转移有关,它们可能共同参与了大肠癌发生及淋巴结转移过程。

CCR7在多发性骨髓瘤中的表达及其与髓外病变的关系

目的:检测趋化因子受体-7(CC-chemokine receptor 7,CCR7)在多发性骨髓瘤中的表达水平,探讨其与疾病特征的关系。方法:采用流式细胞术测定53例新诊断的多发性骨髓瘤患者的骨髓浆细胞CCR7的表达水平,分析其与年龄、性别、M蛋白、外周血细胞计数、血生化指标、骨髓浆细胞比例、免疫表型特点、溶骨改变、髓外病变等疾病特征的关系。结果:53例多发性骨髓瘤患者中CCR7阳性者24例,阳性率为45.28%,CCR7阳性组髓外病变发生率高于CCR7阴性组(29.17%vs 3.45%)(P<0.05)。结论:CCR7在多发性骨髓瘤中表达较高,其高表达与髓外病变发生相关,CCR7可能是预测多发性骨髓瘤发生髓外病变的重要指标。

乳腺癌中mTOR、CCR7的表达及与淋巴结转移的关系

目的探讨乳腺浸润性导管癌中哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)与趋化因子受体7(chemokine receptor 7,CCR7)的表达以及与乳腺癌侵袭、转移之间的关系。方法采用免疫组化MaxVision法检测105例乳腺浸润性导管癌、55例转移淋巴结及40例正常乳腺组织中mTOR和CCR7的表达,并分析mTOR和CCR7的表达与乳腺癌侵袭和淋巴结转移的关系以及二者之间的相关性。结果 mTOR在乳腺浸润性导管癌、转移淋巴结及正常乳腺组织中的阳性率分别为68%(71/105)、93%(51/55)、25%(10/40),差异有统计学意义(P<0.05);CCR7在乳腺浸润性导管癌、转移淋巴结及正常乳腺组织中的阳性率分别为74%(78/105)、94%(52/55)、28%(11/40),差异有统计学意义(P<0.05)。在乳腺癌中,mTOR和CCR7的表达呈正相关(rs=0.203,P<0.05)。mTOR和CCR7的高表达均与淋巴结转移有关(P<0.05)。结论mTOR和CCR7的异常高表达可能与乳腺癌的侵袭、转移有关,且检测二者的表达可作为判断乳腺癌转移及预后的预测指标。

CCR7基因修饰未成熟树突状细胞诱导小鼠皮肤移植免疫耐受的研究

目的研究CCR7基因重组腺病毒体外转染未成熟树突状细胞(imDCs)对小鼠同种异体皮肤移植免疫耐受的影响。方法小鼠骨髓细胞经梯度离心及rmIL-4、rmGM-CSF诱导培养未成熟树突状细胞;CCR7重组腺病毒经增强离心法转染未成熟树突状细胞;体外观察转染细胞混合淋巴细胞反应;取CCR7修饰imDCs于皮肤移植前2d、移植后第5天,经腹部注入受体小鼠,观察皮肤移植物存活时间和病理变化。结果CCR7基因成功转染入imDCs;腺病毒转染后imDCs刺激T细胞增殖的能力较imDCs组增强但弱于mDCs组,IL-10可以明显降低刺激能力;CCR7腺病毒转染组皮肤存活时间长于转染前,IL-10能显著延长皮肤存活时间。结论CCR7重组腺病毒转染imDCs后,imDCs刺激T细胞增殖的能力部分增强,皮肤移植物存活时间明显延长。

三阴性乳腺癌(TNBC)组织中CCR4和CCR7的表达及意义

目的探讨三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中CC族趋化因子受体4(ccchemokine receptor 4,CCR4)和CCR7的表达意义及其与临床病理特征和预后之间的相关性。方法应用免疫组织化学染色SP法检测TNBC、HER-2过表达型乳腺癌、TNBC癌旁组织及乳腺良性肿瘤(3组,各38例)和管腔型乳腺癌组织(40例)中CCR4和CCR7的表达。结果在TNBC组织中,CCR4和CCR7的表达率分别为47.4%(18/38)和50%(19/38),与非TNBC组相比,差异有统计学意义(P值分别为0.001和0.004)。CCR4表达与TNBC肿瘤直径(P=0.023)、腋窝淋巴结转移(P=0.006)、肿瘤分期(P=0.016)和远处转移(P=0.028)相关。Kaplan-Meier生存分析显示CCR4表达与TNBC患者总生存率(overall survival,OS)相关(P=0.018)。CCR7表达和TNBC患者的腋窝淋巴结转移相关(P=0.038),而与TNBC患者无病生存率(disease freesurvival,DFS)和OS无关。多因素分析显示腋窝淋巴结转移是TNBC患者DFS的独立预测因素(P=0.025),而CCR4是TNBC患者OS的独立预测因素(P=0.022)。结论 TNBC中CCR4和CCR7的表达与腋窝淋巴结转移相关;CCR4可作为TNBC患者预后的独立预测指标。

CCR7上调MMP-9表达促进非小细胞肺癌转移

背景与目的 趋化因子激素受体(CC chemokine receptor7,CCR7)与非小细胞肺癌(non-small celllung cancer,NSCLC)的淋巴结转移密切相关,但CCR7促进其淋巴结转移的机制尚不明了。本研究通过观察CCR7和MMP-9在NSCLC组织中的表达和相互关系,探讨CCR7促进NSCLC淋巴结转移的机制。方法 应用免疫组织化学染色(SP法)检测90例NSCLC组织中CCR7、MMP-9的表达;将BE1细胞经趋化因子CCL19处理24h后,应用RT-PCR和Western blot方法检测MMP-9mRNA和蛋白表达水平。结果 免疫组织化学结果显示:CCR7主要表达于癌细胞胞质和(或)胞膜,MMP-9主要表达于癌细胞胞质,NSCLC中CCR7、MMP-9阳性表达率分别为70%(63/90)和65.5%(59/90),χ2检验显示CCR7和MMP-9表达与NSCLC的临床病理分期(P=0.003,P=0.001)和淋巴结转移(P=0.004,P=0.003)密切相关,而与年龄、组织学类型、分化程度无关(P>0.05)。此外,CCR7和MMP-9表达正相关(r=0.342,P=0.001)。CCL21处理组BE1细胞后MMP-9mRNA和蛋白水平均上调(P<0.05)。结论 CCR7和MMP-9表达与NSCLC侵袭转移密切相关,CCL19/CCR7通过上调NSCLC中MMP-9表达促进其转移。

CCR7在甲状腺乳头状癌组织中的表达及意义

目的:检测趋化因子受体CCR7在甲状腺乳头状癌组织中的表达,探讨CCR7表达与淋巴结转移的关系。方法:采用免疫组织化学法检测30例乳头状癌标本中CCR7的表达。结果:CCR7在30例乳头状癌组织中阳性表达率为56.7%(17/30),其中淋巴结转移组的阳性表达率为92.3%(12/13),而无淋巴结转移组的阳性表达率为29.4%(5/17),差异有统计学意义(P<0.01);CCR7的表达与患者性别、年龄及肿瘤大小无关(P>0.05)。结论:甲状腺乳头状癌组织中CCR7的表达与淋巴结转移关系密切,对甲状腺乳头状癌手术方案的选择及药物靶向治疗具有重要意义。

趋化因子受体CCR7在结直肠癌中的异常表达

目的:检测趋化因子受体CCR7在结直肠癌中的表达状态,探讨CCR7在结直肠癌发病中的作用.方法:采用免疫组化检测标本中CCR7蛋白表达,逆转录PCR(RT-PCR)检测CCR7mRNA表达,Westernblotting检测结肠癌细胞CCR7蛋白表达.结果:45例结直肠癌组织标本检出CCR7mRNA表达,而其相应的癌旁组织中12例检出(χ2=34.44,P<0.01).34例结直肠癌组织标本检出CCR7蛋白表达,其相应的癌旁组织中,则有6例检出(χ2=28.51,P<0.01).结肠癌细胞SW-480中CCR7mRNA和蛋白表达显著,而在HT-29中表达较弱.结论:CCR7参与结直肠癌的发病过程,其表达与结直肠癌转移有关.

趋化因子受体CCR7在NSCLC与转移淋巴结中的表达关系及意义

背景与目的恶性肿瘤的靶向转移是近年来研究的热点,研究已经证实恶性肿瘤的转移是一种非随机的、有组织器官选择性的高度组织化的过程,本研究通过对趋化因子受体CCR7在非小细胞肺癌及其转移淋巴结中的表达状况进行分析,初步探讨趋化因子受体CCR7在非小细胞肺癌中的表达及其与淋巴结转移之间的关系和意义。方法用兔抗人CCR7抗体免疫组化染色检测肺腺癌17例,鳞癌17例,腺鳞癌12例,大细胞肺癌4例和转移淋巴结28例中CCR7的表达情况。阴性对照标本采用炎性假瘤5例,正常肺组织20例。结果判定在双盲法下进行,每张切片由两名病理医师分别判断。结果1.CCR7在癌组织和转移淋巴结中的表达高于正常肺组织(P<0.005);2.转移淋巴结中CCR7表达与癌组织中CCR7的表达相比无差异(P=0.177);3.CCR7在癌组织中的表达与淋巴结转移相关,淋巴结转移组高于无淋巴结转移组(P=0.016);4.随着临床分期的增加,CCR7表达有增高趋势(P=0.003)。结论CCR7蛋白主要在肺癌肿瘤细胞与转移淋巴结中表达,而在正常肺组织中未见表达,其表达水平可能与非小细胞肺癌淋巴转移有关。

非小细胞肺癌中D2-40、CCR7的表达与淋巴结转移的关系

目的探讨CCR7及D2-40在非小细胞肺癌中的表达与淋巴结转移的关系。方法采用快捷免疫组织化学Max Vision法检测104例非小细胞肺癌、10例非小细胞癌旁组织及5例正常肺组织CCR7和D2-40的表达,并以D2-40标记淋巴管内皮细胞,计算微淋巴管密度(MLVD)。结果非小细胞肺癌与正常肺组织MLVD计数分别为(7.81±2.22)、(4.20±1.07),非小细胞肺癌中MLVD明显增高(P<0.001)。非小细胞肺癌中47例淋巴结阳性组与57例淋巴结阴性组MLVD计数分别为(8.39±2.35)、(7.33±2.00),淋巴结阳性组MLVD计数显著高于淋巴结阴性组(P<0.001)。104例非小细胞肺癌CCR7阳性率为82.7%;癌旁肺组织CCR7阳性率为30%;正常肺组织CCR7阳性率为20%。淋巴结阳性组与淋巴结阴性组CCR7阳性率分别为87.2%(41/47)、61.4%(35/57)。χ2值为87.4,P值为0.03。CCR7阳性组MLVD(8.51±2.03)高于CCR7阴性组MLVD(6.01±1.59),两者比较差异具有统计学意义(P<0.05)。D2-40标记的MLVD与CCR7表达呈正相关(相关系数r=0.597,P<0.000)。结论在非小细胞肺癌中,淋巴结阳性组CCR7高表达,与D2-40标记的MLVD正相关。D2-40仅表达于淋巴管内皮细胞,且肿瘤细胞CCR7高表达属淋巴结转移早期事件,联合检测CCR7与D2-40有望成为判断淋巴结转移更为有效的指标。并可能为今后治疗非小细胞肺癌及抑制淋巴结转移提供有力的理论依据。