CXCR4在胃癌中的表达及其意义

目的:观察趋化因子受体CXCR4在胃癌中的表达及其与胃癌临床病理因素的关系.方法:选取中国医科大学第一临床学院肿瘤外科确诊的胃癌患者30例,收集胃癌及相应癌旁组织,采用RT-PCR技术研究趋化因子受体CXCR4在各种病理类型、不同演进阶段的表达情况、表达分布情况.结果:趋化因子受体CXCR4在有淋巴结转移组的表达指数(0.34±0.12)显著高于无转移组的表达指数(0.23±0.07)(P<0.05),依照UICC分期标准其 pN1组(0.26±0.04)与pN2 pN3组(0.51±0.09) 也有显著性差异(P<0.05).而与大体分型、浸润程度、分化程度、生长方式在本实验中无明显关系.结论:趋化因子受体CXCR4的表达与淋巴结转移正相关,检测其表达对于推测胃癌淋巴结转移发生与否和转移程度有一定意义.     

趋化因子受体CXCR4在下咽鳞癌组织中的表达及其意义

背景与目的:有研究表明,趋化因子受体CXCR4及其配体SDF-1(stromal cell-derived factor1)与肿瘤的增殖、分化和转移等恶性表现密切相关.本研究探讨趋化因子受体CXCR4在下咽鳞状细胞癌(下咽鳞癌)组织中的表达情况及其与下咽鳞癌各临床病理资料的关系,为临床治疗提供理论基础.方法:下咽鳞癌原发灶组织标本43例,其中淋巴结阳性34例,淋巴结阴性9例,通过免疫组化技术检测CXCR4表达,并取相应27例正常癌旁下咽部组织与原发灶作为对照,探讨其与下咽鳞癌的关系.结果:下咽鳞癌原发灶及正常下咽部对照组织CXCR4阳性表达率分别为95.3%和22.2%(P<0.01).淋巴结阳性转移灶CXCR4表达率(82.4%)显著高于阴性淋巴结(22.2%)(P<0.01).随着病理分化程度的降低,CXCR4阳性表达率增加(P<0.05).结论:CXER4在下咽鳞癌组织呈高表达,其表达水平与肿瘤T分期、有无淋巴结转移、病理分级有关,对评估下咽癌的生物学行为有意义.     

胃癌原发灶和淋巴结转移灶HER2表达的临床意义

目的 观察HER2在胃癌原发灶和淋巴结转移灶中的表达及其临床意义.方法 选取胃癌患者140例,其中淋巴结转移94例.采集胃癌患者的原发灶、淋巴结转移灶及癌旁组织,采用免疫组织化学法(Elivision)方法检测3种组织中HER2蛋白表达情况.结果 140例胃癌原发灶组织中HER2蛋白阳性表达与胃癌TNM分期、浸润深度及淋巴结转移有关(P<0.05),而与患者性别、年龄和分化程度无关(P>0.05),癌旁组织中HER2表达与性别、年龄、分化程度、TNM分期、浸润深度及淋巴结转移均无关(P>0.05);HER2蛋白在胃癌原发灶、淋巴结转移灶中表达水平均高于癌旁组织,差异有统计学意义,而94例淋巴结转移灶和对应的胃癌原发灶中HER2表达的差异无统计学意义;94例有淋巴结转移的患者淋巴结转移灶与原发灶HER2表达一致率为89.4%,两类标本HER2表达状态具有一致性(Z=6.386,P<0.001).结论 胃癌HER2蛋白的阳性表达与胃癌TNM分期、浸润深度及淋巴结转移有关,提示HER2的表达与胃癌的浸润转移有关;胃癌原发灶和淋巴结转移灶HER2的表达具有较好的一致性,患者在不能获取原发病灶的情况下,检测转移灶中HER-2可能为靶向治疗的选择提供依据,为晚期胃癌患者带来希望.     

宫颈癌组织中CCR7及CXCR4的表达及与临床病理特征的关系

目的探讨CC族趋化因子受体7(CCR7)及CXC族趋化因子受体4(CXCR4)在宫颈癌组织中的表达情况及与临床病理特征的关系。方法选取2015年2月至2016年2月间深圳市蛇口人民医院收治的行子宫切除术的82例宫颈癌患者为观察组,另选取同期体检筛查的26例宫颈上皮组织阴性者为对照组。采用免疫组化SP法检测两组CCR7和CXCR4的表达,并分析CCR7和CXCR4的表达与临床病理特征的关系。结果观察组中CCR7的阳性表达率为58.5%,明显高于对照组的26.9%,观察组中CXCR4的阳性表达率为52.4%,明显高于对照组的19.2%,差异均有统计学意义(均P<0.05)。宫颈癌组织中,CCR7的阳性表达与FIGO分期、肿瘤直径、间质浸润深度及淋巴结转移均有关,差异均有统计学意义(均P<0.05),与年龄、组织病理类型、阴道浸润及子宫旁浸润无关,差异均无统计学意义(均P>0.05)。CXCR4的阳性表达与淋巴结转移有关,差异有统计学意义(P<0.05),与年龄、FIGO分期、组织病理类型、肿瘤直径、间质浸润深度、阴道浸润及子宫旁浸润无关,差异均无统计学意义(均P>0.05)。宫颈癌组织中CCR7与CXCR4的表达呈正相关,差异有统计学意义(P<0.05)。结论 CCR7及CXCR4在宫颈癌组织中呈高表达,两者均在宫颈癌淋巴转移中发挥重要作用,与宫颈癌患者预后效果密切相关。     

胃癌中CXCR4 mRNA的表达量及其临床意义

摘 要：［目的］ 探究胃癌组织中与胃癌进展相关的趋化因子受体4（C-X-C motif chemokine receptor 4,CXCR4）的表达量及其临床意义。［方法］ 先根据TCGA数据库,对300余例患者胃癌组织及癌旁组织的CXCR4 mRNA表达量进行差异性分析,并与病理参数进行相关性分析。再使用逆转录聚合酶链式反应（RT-PCR）和免疫组化（immunohistochemistry,IHC）技术检测2018年7月至2022年11月陕西省人民医院收治的92例患者胃癌组织标本中CXCR4 mRNA的表达量并分析其与预后和病理参数的相关性。［结果］ TCGA数据及临床数据分析均显示,胃癌组织的CXCR4 mRNA表达水平显著高于癌旁组织（P＜0.001）。TCGA数据分析显示,CXCR4 mRNA表达量与肿瘤浸润深度及低分化程度呈正相关（OR=1.297、1.437,P均＜0.05）。临床数据分析显示,CXCR4 mRNA表达量与肿瘤远处转移及分化程度呈正相关（OR=7.717、3.254,P均＜0.05）。TCGA数据及临床数据Kaplan-Meier生存分析均显示,与CXCR4 mRNA低表达组相比,高表达组胃癌患者生存时间明显缩短（P=0.008、0.001）。［结论］ 胃癌组织中CXCR4 mRNA过表达,与肿瘤的进展、浸润、转移密切相关,其高表达提示胃癌患者的不良预后。CXCR4 mRNA可能成为胃癌诊断和靶向治疗新的候选标志物。     

CXCL12及受体CXCR4在卵巢上皮性癌中的表达及其临床意义

目的:探讨趋化因子CXCL12及其受体CXCR4在卵巢上皮性癌组织中的表达及与临床病理特征和预后的关系。方法:采用免疫组织化学SP法检测6例正常卵巢表面上皮、44例卵巢上皮性癌原发灶和30例相应大网膜转移灶组织中的CXCL12和CXCR4蛋白表达。结果:正常卵巢表面上皮无CXCL12和CXCR4蛋白表达;卵巢上皮性癌原发灶的CXCL12和CXCR4表达阳性率分别为91%和59%。CXCL12表达强度与术中腹水量有显著相关性(P=0.014)。难治复发组的CXCR4阳性率(81%)显著高于无复发组(28%,P<0.001)。单因素分析显示:CXCR4阳性表达的患者中位数肿瘤无进展生存时间和总生存时间(15个月、27个月)明显短于CXCR4阴性表达者(>21个月、>32个月,分别为P<0.001和P=0.017)。多因素分析显示:CXCR4表达和残余灶大小是影响卵巢上皮性癌患者的肿瘤无进展生存时间和总生存时间的独立预后因素。结论:CXCR4在卵巢上皮性癌中的表达阳性率较高,是影响其预后的独立指标之一。     

结肠癌组织中趋化因子受体CXCR4和基质金属蛋白酶MMP-2的表达及意义

目的观察趋化因子受体CXCR4和基质金属蛋白酶MMP-2的表达与结肠癌各项临床指标间的关系。方法采用免疫组织化学S-P法检测64例Ⅰ-Ⅳ期结肠癌组织石蜡包埋标本和相应癌旁正常结肠组织标本中CXCR4、MMP-2的表达。结果64例癌组织中37例呈CXCR4阳性,39例呈MMP-2阳性;与癌旁正常组织比较均有统计学意义;CXCR4、MMP-2表达均只与淋巴结转移与否有关．而与浸润深度、分化程度、临床分期等无关;CXCR4的表达与MMP-2的表达呈正相关。结论CXCR4、MMP-2可能与结肠癌的淋巴结转移有关,且二者在结肠癌淋巴结转移过程中可能存在某种调控或协同作用,联合检测CXCR4、MMP-2可预测结肠癌淋巴结及远处转移情况并指导临床用药。     

CXCR5/CXCL13及ERK1在甲状腺乳头状癌中的表达及意义

目的:观察甲状腺乳头状癌及其转移灶中CXCR5/CXCL13及ERK1的表达,探讨其在肿瘤发生发展中的可能作用。方法:选取2014年1月到2016年5月在本院进行手术的110例甲状腺乳头状癌患者及同期手术的结节性甲状腺肿患者,采用免疫组化法检测CXCR5/CXCL13及ERK1在甲状腺乳头状癌及其转移灶中的表达量。结果:CXCL13、CXCR5及ERK1在甲状腺乳头状癌及其转移淋巴结中的表达均高于正常腺体组织及结节性甲状腺肿患者（P<0.05）。CXCL13、CXCR5及ERK1蛋白在甲状腺乳头状癌中的表达与年龄和性别无关,与淋巴结转移呈正相关（P<0.05）。CXCR5/CXCL13蛋白的表达与ERK1呈正相关。结论:趋化因子CXCL13及其受体CXCR5在甲状腺乳头状癌发生发展及其淋巴结转移中发挥了重要作用,为临床甲状腺乳头状癌的诊断及靶向治疗提供一定的理论依据。     

结肠癌组织中CXCR2的临床表达意义

目的 探讨结肠癌组织内CXC趋化因子受体2(CXCR2)的临床表达意义。方法 选取73例结肠癌患者作为研究对象,所有患者均于手术中采集肿瘤组织及癌旁组织,开展免疫组织化学法检测组织中CXCR2表达。比较肿瘤组织与癌旁组织内CXCR2表达差异;分析不同CXCR2表达患者年龄、性别、体质量指数、肿瘤分期、淋巴结转移、分化程度、肿瘤直径等基础资料间差异;随访3年,比较不同CXCR2表达患者远期肿瘤复发转移情况。结果 肿瘤组织TIM-3阳性表达率高于癌旁组织,差异有统计学意义(P<0.05)。肿瘤分期Ⅲ～Ⅳ期、有淋巴结转移、低分化程度、肿瘤直径≥3 cm患者TIM-3表达阳性率高于肿瘤分期Ⅰ～Ⅱ期、无淋巴结转移、中高分化程度、肿瘤直径<3 cm患者,差异有统计学意义(P<0.05)。随访3年,73例患者复发转移率为35.62%(26/73); CXCR2阳性表达组复发转移率高于CXCR2阴性表达组,差异有统计学意义(P<0.05)。结论 CXCR2在结肠癌组织内阳性表达率较高,与肿瘤分期、肿瘤直径、分化程度密切相关,且CXCR2阳性表达患者易伴有淋巴结转移,预后更差,可...     

趋化因子受体CXCR4在食管癌中的表达及临床意义

[目的]探讨CXCR4在食管癌中的表达及意义。[方法]应用免疫组织化学方法检测82例食管癌组织、20例癌旁食管组织中CXCR4的表达。[结果]CXCR4在癌旁食管组织无表达,在82例食管癌组织中的阳性表达率为64.6%(53/82)。CXCR4表达与食管癌患者的年龄、性别无关,而与分化程度、TNM分期、浸润深度、组织学类型和淋巴结转移有关。[结论]CXCR4在食管癌中高表达,CXCR4可能是促进食管癌侵袭和转移的一个重要分子。     

CXCR4和CXCR7在肿瘤中的研究进展

以往的研究认为趋化因子受体4(chemokine receptor 4,CXCR4)是趋化因子CXCL12的唯一受体,CXCL12/CXCR4生物轴在肿瘤发展过程中起重要作用,然而最近研究发现CXCL12尚存在CXCR7这一新的受体,并且CXCL12/CXCR7生物轴同样对肿瘤的发生发展起重要作用.本文就有关趋化因子受体CXCR4和CXCR7在肿瘤中的表达、促进肿瘤增殖和转移、促进血管新生以及肿瘤治疗等方面的研究作一综述.     

The chemokine receptors CXCR4 and CXCR3 in cancer

Chemokines comprise a superfamily of at least 46 cytokines that were initially described based on their ability to bind to 18 to 22 G protein-coupled receptors to induce the directed migration of leukocytes to sites of inflammation or injury. In addition to mediating cellular migration, chemokine/chemokine receptor pairs have been shown to affect many cellular functions, including survival, adhesion, invasion, and proliferation, and to regulate circulating chemokine levels. Most malignancies also express one or more chemokine receptors. Early studies established a role for CXCR4 and CXCR7 in mediating breast cancer metastasis, but other chemokine receptors, including CXCR3, now are implicated in several malignancies as biomarkers of tumor behavior as well as potential therapeutic targets. This review summarizes our current understanding regarding the contribution of CXCR4 and CXCR3 to tumor behavior and how receptor expression is regulated, transduces intracellular signals, and contributes at the molecular level to tumor behavior. It also describes recent therapeutic approaches that target these receptors or their ligands.     

Clinical significance of CXCR3 and CXCR4 expression in primary melanoma

Tumor cell migration involved in metastases is a tightly regulated, nonrandom process. Chemokines have been identified as critical molecules guiding cell migration. We performed a prospective study to analyze a possible association between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma and clinical outcome. Forty primary melanomas were available for analysis; 57% of the tumors expressed CXCR3 and 35% expressed CXCR4 by melanoma cells. At initial diagnosis, 5 patients had subclinical lymph node involvement and after a median follow-up time of 32 months, 2 additional patients developed regional lymph node metastases and 5 patients developed distant metastases. The expression of CXCR4, but not CXCR3, by melanoma cells in primary lesions was significantly associated with the presence of ulceration, increased tumor thickness, a greater risk of developing regional and distant metastases and a higher mortality rate. Our study underscores the value of CXCR4 expression as a useful marker for predicting outcome in patients with localized melanoma. In addition, our findings support that, among chemokine receptors, CXCR4 might be an appropriate therapeutic target for adjuvant therapy in patients at risk for metastatic disease.     

Opposing roles of CXCR4 and CXCR7 in breast cancer metastasis

Introduction  

CXCL12-CXCR4 signaling has been shown to play a role in breast cancer progression by enhancing tumor growth, angiogenesis, triggering cancer cell invasion in vitro, and guiding cancer cells to their sites of metastasis. However, CXCR7 also binds to CXCL12 and has been recently found to enhance lung and breast primary tumor growth, as well as metastasis formation. Our goal was to dissect the contributions of CXCR4 and CXCR7 to the different steps of metastasis - in vivo invasion, intravasation and metastasis formation.     

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis. We previously demonstrated that forced expression of CXCR3 promotes colon cancer metastasis preferentially to the draining lymph nodes (LNs), with poor prognosis. Using clinical colorectal cancer (CRC) samples, here, we show that expressions of CXCR3 and CXCR4 are significantly higher in metastatic foci within LNs and liver compared to primary tumors, whereas ligands for CXCR3 and CXCR4 are not. We also have demonstrated that some human CRC cell lines constitutively express both CXCR3 and CXCR4, and that activation of CXCR3 strengthens the CXCR4‐mediated cell migration in vitro in a synergistic manner. By constructing SW620 cell lines with reduced expression of CXCR3 and/or CXCR4 using microRNA, we investigated in vivo metastatic activities in a mouse rectal transplantation model. Six weeks after inoculation, CXCR3‐, CXCR4‐, and CXCR3/CXCR4 double‐knockdowns significantly reduced metastasis to LNs, liver and lungs, compared to the control (p < 0.05). Importantly, its suppressive effect on LN metastasis was significantly stronger in CXCR3‐ and CXCR3/CXCR4 double‐knockdowns. In addition, CXCR3‐ and CXCR3/CXCR4 double‐knockdowns significantly decreased the dissemination of cancer cells to liver and lungs, even after 2 weeks. These results indicate that targeting CXCR3 and CXCR4 can be a promising therapy against CRC metastasis.     

CXCR1、CXCR2在口腔鳞癌中的表达及意义

目的　探讨CXCR1、CXCR2的表达与口腔鳞癌生物学行为的关系及意义.方法　应用免疫组织化学技术检测57例口腔鳞癌手术切除标本和10例正常口腔黏膜标本中CXCR1、CXCR2的表达情况,分析其与病变类型及临床病理特征的关系.结果　口腔鳞癌标本中41例(71.9％) CXCR1呈阳性表达,35例(61.4％) CXCR2呈阳性表达.CXCR1与口腔鳞癌的病理分级、临床分期及淋巴结转移关系密切,CXCR2与口腔鳞癌的临床分期及淋巴结转移关系密切.结论　CXCR1、CXCR2在口腔鳞癌的发生、发展中起重要作用,是口腔鳞癌早期诊断和预后的潜在生物学参考指标.     

The dynamic yin-yang interaction of CXCR4 and CXCR7 in breast cancer metastasis

The contribution of CXCR7 to the tumor microenvironment has introduced a new level of complexity to CXCL12 signaling in breast cancer. In the previous issue of Breast Cancer Research, Hernandez and colleagues delineate the roles of CXCR4 and CXCR7 in tumor invasion and metastasis. The authors demonstrate that co-expression of CXCR7 and CXCR4 results in inhibition of CXCL12-mediated invasion, reduced intravasation of tumor cells into the vasculature, and fewer lung metastases compared with parental tumors. The results of this study suggest the combination of small molecule inhibitors of CXCR4 and CXCR7 could dramatically reduce invasion, intravasation, and metastasis and could be highly beneficial for the treatment of invasive breast cancer.     

CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion

The aggressiveness of malignant melanoma is associated with differential expression of CXCL-8 and its receptors, CXCR1 and CXCR2. However, the precise functional role of these receptors in melanoma progression remains unclear. In this study, we investigate the precise functional role of CXCR1 and CXCR2 in melanoma progression. CXCR1 or CXCR2 were stably overexpressed in human melanoma cell lines, SBC-2 (non-tumourigenic) and A375P (low-tumourigenic) exhibiting low endogenous expression of receptors. Functional assays were performed to study the resulting changes in cell proliferation, motility and invasion, and in vivo tumour growth using a mouse xenograft model. Our data demonstrated that CXCR1- or CXCR2-overexpressing SBC-2 and A375P melanoma cells had enhanced proliferation, chemotaxis and invasiveness in vitro. Interestingly, CXCR1 or CXCR2 overexpression in SBC-2 cells induced tumourigenicity, and A375P cells significantly enhanced tumour growth as examined in vivo. Immunohistochemical analyses showed significantly increased tumour cell proliferation and microvessel density and reduced apoptosis in tumours generated from CXCR1- or CXCR2-overexpressing melanoma cells. CXCR1- or CXCR2-induced modulation of melanoma cell proliferation and migration was observed to be mediated through the activation of ERK1/2 phosphorylation. Together, these studies demonstrate that CXCR1 and CXCR2 play essential role in growth, survival, motility and invasion of human melanoma.     

乳腺癌中CXCR4的表达及其与Hedgehog信号通路的相关性

目的 检测乳腺癌组织中CXCR4及Smoothened (Smo)、Patched (Ptch)的表达,对CXCR4表达的临床意义进行分析,并评价CXCR4与Smo、Ptch之间的相关性.方法 以免疫组织化学染色法检测124例乳腺癌组织中CXCR4、Smo、Ptch的表达情况,并对其结果进行分析.结果 乳腺癌组织中CXCR4阳性表达率为66.9％,CXCR4与乳腺癌淋巴结转移呈正相关(r=0.181,P=0.044);Smo、Ptch阳性表达率分别为58.9％和64.5％,与CXCR4表达呈正相关(r=0.189,P=0.036;r=0.230,P=0.0l0).结论 CXCR4的表达与乳腺癌淋巴结转移有关,与Smo、Ptch表达呈正相关,当其与Hedgehog信号通路同时表达时或许与乳腺癌的复发风险增高相关.