Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues

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Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(EGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-EGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them.

Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.

Increased hepatic expression of insulin-like growth factor-Ⅰreceptor in chronic hepatitis C

瞄准：尽管增加像胰岛素的生长因素 -- 我受体(IGF 红外) 基因表示在肝细胞癌被报导了，在长期的丙肝(CHC ) 估计 IGF 红外的研究和肝硬化是少见的。我们因此试图与 CHC 从病人在肝评估 IGF 红外和 IGF-I mRNA 表示。方法：IGF 红外和 IGF-I mRNA 内容被半量的 RT-PCR 决定， IGF 红外蛋白质表示由在以前与 CHC 从病人获得的肝的织物(34 个病人) 并且在以后的 immunohisto 化学是坚定的(10 个病人) 有 interferon-alpha 和 ribavirin 的治疗。结果：IGF 红外 mRNA 内容的增加在从所有 CHC 病人以及从与正常的肝相比跟随 orthopic 移植(评估正常的肝的一次尝试) 的 6 个尸体肝施主获得的肝的织物被观察，当没有相关修正在 IGF-I mRNA 内容被检测时。组织化学的结果显示出的免疫在 IGF 红外 mRNA 的加薪满足，这与 ductular 反应并且到在 hepatocytes 的增加的 IGF 红外表示相关。在 IGF 红外 mRNA 内容的减少在在治疗以后完成了持续 virological 反应的病人被观察，建议处于肝的损坏的改进。结论：在有 CHC 的病人的 hepatocytes 的 IGF 红外表示的起来规定能组成一次尝试刺激 hepatocyte 新生。考虑到那个肝是有 IGF-I 的高水平的机关，我们在尖锐、长期的肝的损坏以后发现增加的 IGF 红外表示加亮需要让另外的研究阐明在肝的 IGF-I 的角色新生。

Effects of ethanol on insulin-like growth factor-Ⅰ system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase

AIM: To evaluate the effects of ethanol on the insulin- like growth factor-Ⅰ (IGF-Ⅰ) system involved in c-Jun N-terminal kinase (JNK1/2) and alcoholdehydrogenase (ADH) activity in primary cultured rat hepatocytes. METHODS: Hepatocytes isolated from male Sprague-Dawley rats were incubated with various concentrations of ethanol for different durations of time. The cells were pretreated with SP600125 (10 μmol/L) and 4-MP (200 μmol/L), and then treated with ethanol (200 mmol/L). We then measured IGF-Ⅰ secretion, IGF-Ⅰ mRNA expression, cell viability and JNK1/2 activity by radioimmunoassay, RT-PCR, MTT assay and Western blot, respectively (n = 6). RESULTS: Ethanol induced the activity of phospho (p)-JNK1/2, reaching a maximum at 60 min and then decreasing at 180 min. The effects of ethanol on the IGF-Ⅰ system were increased at 60 min (secretion: 7.11 ± 0.59 ng/mg protein vs 4.91 ± 0.51 ng/mg, mRNA expression: 150.2% ± 10.2% vs 101.5% ± 11.3%, P = 0.045) and then decreased at 180 min (secretion: 3.89 ± 0.25 ng/mg vs 5.4 ± 0.54 ng/mg protein; mRNA expression: 41.5% ± 10.4% vs 84.7% ± 12.1%, P = 0.04), however cell viability was decreased in a dose- and time-dependent manner. SP600125 blocked the ethanol-induced changes (at 60 min). Additionally, 4-methylpyrazole prevented the ethanol-induced decreases in the IGF-Ⅰ system, cell viability and p-JNK1/2 activity (at 180 min). CONCLUSION: This study suggests that ethanol- induced p-JNK1/2 activation is associated with the IGF-Ⅰ system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-Ⅰ system and cell viability.

The significance of proto-oncogene HGF/SF receptor c-Met mRNA expression in nasopharyngeal carcinoma

Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.

Effect of Bushenwenyanghuayu decoction on nerve growth factor and bradykinin/bradykinin B_1 receptor in a endometriosis dysmenorrhea mouse model

OBJECTIVE:To observe the effects of Bushenwenyanghuayu decoction(BD),a Traditional Chinese Medicine(TCM),on the serum concentration of nerve growth factor(NGF) and bradykinin(BK),and protein and mRNA levels of NGF and bradykinin B_1receptor(BKB1R) in a mouse model of endometriosis dysmenorrhea.METHODS:Seventy-five experimental female BALB/c mice were randomly divided into five groups,15 mice each:sham,model,BD high dose(61.67 g/kg),BD low dose(15.42 g/kg),and gestrinone(0.4 mg/kg) groups.All the mice except for those in the sham group underwent auto-transplantation surgery and were gavaged estradiol valerate(0.5 mg/kg,daily for 12 days) after surgery.On the 12 th day,1 h after administration,writhing response was induced by intraperitoneal injection of oxytocin at 2 U/mouse.The writhing frequency and latency were recorded and the volume of the ectopic foci was measured.The concentration of serum NGF and BK was detected by enzyme-linked immunosorbent assay,the protein expression of NGF and BKB1 R was tested by immunohistochemistry and western blotting,and NGF and BKB1 R mRNAs were detected by real-time PCR.RESULTS:Compared with the model group,the volume of the ectopic foci in the treatment groups was significantly lower(P < 0.01),the writhing frequency was decreased(P < 0.05),and the writhing latency was prolonged(P < 0.01).Compared with the sham group,serum NGF and BK levels in the model group were significantly increased(P <0.01).There were positive correlations for writhing frequency among the NGF and BK groups(P <0.01).The serum NGF and BK levels were significantly lower in the treatment groups than the model group(P < 0.05).The protein expression of NGF,BKB1 R was significantly decreased in the treatment groups compared with the model group(P < 0.01).NGF and BKB1 R mRNA expression was significantly decreased in the treatment groups compared with the model group(P < 0.01).CONCLUSION:NGF and BK/BKB1 R may play an important role in the development of endometriosis-associated dysmenorrhea,and BD was found to inhibit the development of endometriosis and relieve dysmenorrhea by influencing NGF and BK/BKB1 R mRNA and protein levels.

MACC1、HGF和C-met蛋白在卵巢上皮性癌中的表达及其意义

目的探讨结肠癌转移相关基因1(metastasis-associated in colon cancer-1,MACC1)、肝细胞生长因子(HGF)和C-met蛋白在卵巢上皮性癌中的表达及其意义。方法采用免疫组织化学和Western blot技术检测20例正常卵巢组织、19例卵巢良性上皮性肿瘤组织和52例卵巢上皮性癌组织中MACC1、HGF和C-met蛋白的表达情况,分析三者与卵巢癌临床病理指标的关系及三者在卵巢癌组织中表达的相关性。结果 MACC1、HGF和C-met蛋白在卵巢上皮性癌组织中的阳性率分别为73.1%、63.5%和78.8%,相对表达量分别为0.72±0.05、0.64±0.04和0.79±0.04,均显著高于正常卵巢和良性肿瘤组织(P<0.05)。在卵巢上皮性癌中,MACC1、HGF和C-met异常高表达与临床分期、组织分化和淋巴结转移相关,临床分期越晚、组织分化越差、伴随淋巴结转移的癌组织中MACC1、HGF和C-met蛋白表达越高(P<0.05)。卵巢上皮性癌中MACC1蛋白的表达与HGF和C-met蛋白的表达呈正相关(r=0.350,P=0.011;r=0.429,P=0.002),HGF蛋白与C-met蛋白表达呈正相关(r=0.487,P=0.000)。结论 MACC1具有作为晚期卵巢癌分子标志物的潜在价值,MACC1、HGF和C-met异常可能协同参与卵巢上皮性癌的恶性进展。

子宫内膜异位症患者肝细胞生长因子及其受体c-Met的表达

目的研究肝细胞生长因子(HGF)及其受体c-Met在子宫内膜异位症发病机制中的作用。方法采用mRNA原位杂交和免疫组织化学技术检测经腹腔镜手术及病理证实的54位子宫内膜异位症妇女(Ⅰ/Ⅱ期患者28例,Ⅲ/Ⅳ期患者26例)在位和异位内膜组织及24例正常对照组妇女在位内膜HGF、c-Met的分子和蛋白表达。结果子宫内膜异位症患者在位内膜HGF、c-met基因和蛋白阳性表达与异位内膜一致,但阳性切片中,异位内膜阳性细胞数及表达强度高于在位内膜。增生期和分泌期的内膜细胞HGF/c-Met mRNA和蛋白的表达相近,无明显差异。对照组、Ⅰ/Ⅱ期患者在位、异位内膜与Ⅲ/Ⅳ患者在位、异位内膜比较,HGF、c-met基因和蛋白阳性表达频率依次上升,组间差异显著(P<0.01)。Ⅰ/Ⅱ期、Ⅲ/Ⅳ期患者在位和异位内膜与对照组比较,HGF、c-met基因和蛋白阳性表达频率有显著差异;Ⅰ/Ⅱ期患者与Ⅲ/Ⅳ期患者比较,HGF/c-Met阳性表达频率和表达强度均无显著差异。Ⅲ/Ⅳ期患者c-Met强阳性表达频率与对照组比较,有显著差异。结论HGF、c-met基因和蛋白表达与子宫内膜异位症发病机制相关,在位内膜性质的改变可能是子宫内膜异位症发病机制的关键环节。

EGFR激活突变型非小细胞肺癌HGF/MET异质性表达及其临床意义

目的分析不同表皮生长因子受体(EGFR)突变状态,外显子19(E19)缺失(del)和外显子21(E21)L858R基因突变蛋白表达与HGF和MET表达的相关性及其与患者预后和生存之间的关系。方法 S-P免疫组化染色法检测55例EGFR突变的非小细胞肺癌(NSCLC)患者切片中E19 del或E21 L858R、MET和HGF 4种蛋白的表达。Kaplan-Meier绘制生存曲线,log-rank比较生存差异。结果 EGFR突变蛋白阳性者HGF和MET蛋白表达阳性率明显高于EGFR突变蛋白阴性者(P<0.05)。HGF表达阴性者与阳性者比较,其总生存期及无病生存期明显延长(P=0.035和P=0.003)。术后复发或晚期使用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗患者(n=29)中,HGF阴性组较HGF阳性组无疾病进展生存期和总生存期有延长趋势(P=0.19和P=0.10),但差异无统计学意义。结论 HGF可作为EGFR敏感突变NSCLC患者复发和预后生存的判定指标。在EGFR敏感突变的基础上联合HGF指标检测可进一步精确预测EGFR-TKI的疗效和预后生存。

食管癌变进程中HGF、c-met、VEGF蛋白的表达变化及意义

目的研究从正常食管→食管癌前病变→早期食管癌→进展期食管癌过程中,处于不同病变阶段上皮或间质中HGF、c-met及VEGF蛋白的表达变化及意义。方法免疫组化法检测HGF、c-met及VEGF蛋白在正常食管组织20份、低级别上皮内瘤变组织30份、高级别上皮内瘤变组织50份、早期癌组织25份、进展期癌组织25份中的表达。抗体CD34标记血管内皮细胞,测算微血管密度。结果正常食管低级别上皮内瘤变、高级别上皮内瘤变、早期癌变、早期癌、进展期癌上皮组织中,HGF蛋白阳性表达率依次为0(0/20)、3%(1/30)、26%(13/50)、36%(9/25)、60%(15/25);在间质中的阳性表达率依次为0(0/20)、0%(0/30)、30%(15/50)、52%(13/25)、76%(19/25);在食管病变上皮中c-met蛋白阳性表达率依次为0(0/20)、10%(3/30)、30%(15/50)、36%(9/25)、56%(14/25);在间质中VEGF蛋白阳性表达率依次为0(0/20)、3%(1/30)、26%(13/50)、36%(9/25)、52%(13/25);MVD值分别为12.33±1.68、15.72±1.97、20.91±2.20、26.42±1.96、30.01±2.35。5种组织中,HGF、c-met、VEGF蛋白的表达及MVD值差异有统计学意义(P均<0.01)。结论随食管癌变进展,食管上皮组织中HGF、cmet及间质中VEGF蛋白表达均明显升高,HGF/c-met蛋白通路可刺激间质成纤维细胞分泌VEGF蛋白,促进间质微血管形成,加速癌的进展。

肝细胞生长因子及其c-Met受体表达与原发性小肝癌术后复发关系的初步研究

目的 探讨原发性小肝癌 (SHCC)切除术后血清肝细胞生长因子 (HGF)水平和癌组织中c Met受体表达与术后复发的关系。方法 采用ELISA对手术前后血清HGF浓度变化进行检测 ,并利用Western、Northern印迹杂交方法 ,测定肿瘤与非肿瘤组织内c Met蛋白表达量。结果 术前血清HGF浓度为 0 64± 0 15ng/ml,术后 3天为 1 41±0 2 8ng/ml,二者差异有显著性意义 (P <0 0 0 1)。术后 3天血清HGF浓度是术前的 2 3 2± 0 5 5倍。术后HGF的增长倍数与肿瘤组织内c Met蛋白的过度表达在术后复发与未复发者中差别有显著性意义(P <0 0 5 ) ,两年内复发者明显高于两年后复发及未复发者。结论 SHCC切除术后血清HGF水平明显增高 ,肿瘤组织本身c Met蛋白过度表达 。

肝细胞生长因子受体c-met在骨肉瘤中的表达及其临床意义

目的:探讨骨肉瘤组织中肝细胞生长因子受体c-met蛋白的表达情况,分析其临床意义及与预后的关系。方法:应用免疫组织化学方法检测行手术的35例骨肉瘤及13例骨样骨瘤患者标本肝细胞生长因子受体c-met的表达,并分析其与临床因素和预后的关系。结果:骨肉瘤组织中肝细胞生长因子受体c-met的阳性表达率为80%(28/35),而在骨样骨瘤中的表达率为7.7%(1/12),两者比较显著差异(P<0.01);结合临床资料分析,其表达与患者性别、年龄、发病次数、肿瘤体积、病理分型无关(P>0.05),而与临床分期、有无转移有关(P<0.05)。结论:C-met可能在骨肉瘤细胞侵袭、转移的过程中起重要作用;肝细胞生长因子受体c-met可以作为骨肉瘤诊断和预测转移的指标。

HGF/C-Met在舌部鳞状细胞癌的表达及其临床意义

目的:探讨肝细胞生长因子及其受体C-Met蛋白在舌鳞癌中的表达与其临床病理特征之间的关系。方法:通过免疫组化法检测10例正常舌组织、14例舌癌前病变及63例舌鳞癌中肝细胞生长因子、C-Met的表达,数据通过SPSS13.0统计软件非参数秩和检验统计。结果:肝细胞生长因子和C-Met在舌癌、舌癌前病变及正常舌组织的阳性表达率分别为84.1%、57.1%、40.0%和76.2%、35.7%、20.0%,其表达差异均具有统计学意义(P<0.05)。在中、低分化组(90.3%)及有淋巴结转移组(100%)舌鳞癌中肝细胞生长因子的阳性表达率显著高于高分化组(78.1%)及无转移淋巴结组(76.7%);在Ⅲ、Ⅳ期(82.1%)及有淋巴结转移组(85.0%)的舌鳞癌中C-Met阳性表达率显著高于Ⅰ、Ⅱ期(71.4%)及无转移淋巴结组(72.1%),表达差异均具有统计学意义(p<0.05);63例舌癌组织切片中46例HGF及C-Met都有阳性表达,其在舌鳞状细胞癌中的表达显著正相关(P<0.01)。结论:过度表达的HGF/C-Met可作为判断舌鳞状细胞癌生物学行为、恶性潜能和预测淋巴结转移趋势的参考指标。

加味左金丸对大鼠胃癌前病变胃黏膜EGFR、VEGF、C-met、Bcl-2、P53表达的影响

目的:观察加味左金丸对大鼠胃癌前病变胃黏膜EGFR,VEGF,C-met,Bcl-2,P53表达的影响．方法:采用MNNG,0．3 g／L雷尼替丁、56℃ 150 g／L盐水、8．5 g／L脱氧胆酸钠、400 mL／ L乙醇、饥饱失常等多因素造模,存活的43只大鼠随机分为自然恢复组、维甲酸组、加味左金丸高、中、低剂量组,各组大鼠作相应的处理后,免疫组化法检测各组大鼠胃黏膜组织 EGFR,VEGF,C-met,Bcl-2,P53表达水平．结果:加味左金丸高、中组EGFR(25．0％,0 vs 100％,P<0．05,P<0．01),中、低组VEGF(12.5％, 25．0％ vs 100％,均P<0．05)、以及高、中、低组Bcl-2蛋白(12．5％,0,25．0％ vs 100％,P<0．01 或P<0．05)阳性率与自然恢复组比较差异有统计学意义,与维甲酸组比较差异无统计学意义 (P>0．05):加味左金丸各组C—met蛋白阳性率与自然恢复组、维甲酸组比较差异均无统计学意义(P>0．05);各组均未见P53表达．结论:加味左金丸通过下调EGFR,VEGF, Bcl-2蛋白表达而抑制细胞增殖和诱导细胞凋亡,进而发挥治疗大鼠胃癌前病变的作用．

c-Met在食管鳞状细胞癌组织中的表达及其与临床病理的相关性

目的检测食管鳞状细胞癌组织及配对癌旁组织中c-Met蛋白的表达情况,探讨c-Met的表达与食管鳞状细胞癌患者临床病理特点的相关性。方法收集87对甲醛固定,石蜡包埋的食管鳞状细胞癌及配对的癌旁组织标本,所有病例均经病理证实,同时收集患者的临床资料。采用免疫组化的方法检测组织中c-Met的表达情况。结果 c-Met主要表达于细胞膜,表现为胞膜呈棕黄色染色。87例食管鳞癌组织中有29例(33.3%)呈阳性表达。配对癌旁组织中未见c-Met表达。c-Met的表达与食管鳞状细胞癌患者的肿瘤浸润深度、淋巴结转移及临床病理分期(tumor-node-metastasis,TNM)存在显著相关性(分别为P=0.017,P=0.000,P=0.000),而与患者的性别、年龄、肿瘤细胞分化程度、肿瘤大小等无明显相关性(P>0.05)。结论 c-Met在部分食管鳞癌组织中呈高表达,且与患者的肿瘤浸润深度、淋巴结转移及TNM分期存在显著相关性,c-Met的高表达可以作为高侵袭性食管鳞癌的分子标志物。

肝细胞生长因子及C-Met的表达与宫颈癌浸润和转移的关系

目的:研究肝细胞生长因子(HGF)及其受体C-Met在宫颈癌组织中的表达,探讨二者与宫颈癌浸润和转移的关系。方法:采用RT-PCR检测36例宫颈癌组织手术标本及31例正常宫颈组织标本中HGFmRNA和C-MetmRNA的表达,并进行相对定量研究。结果:宫颈癌组织中C-Met的阳性表达率显著高于正常宫颈组织。宫颈癌组织中,淋巴结转移组C-Met的表达水平高于未转移组;临床分期Ⅱ期组的表达水平高于ⅠB期组;中、低分化组的表达水平高于高分化组。结论:宫颈癌组织中存在C-Met的高表达,肿瘤细胞丰富的C-Met受体可能是通过与旁分泌途径获得的HGF结合而在宫颈癌浸润和转移的过程中发挥重要作用。

肝细胞生长因子及其受体c-Met表达与胃癌肝转移的相关性

目的:探讨肝细胞生长因子及其受体c-Met的表达及临床病理因素与胃癌肝转移的关系。方法:应用免疫组化方法检测HGF和及其受体c-Met在胃癌和肝转移癌组织中的表达情况,通过对比两者在原发癌和肝转移癌组织中的不同表达状态,探讨二者及临床病理因素与胃癌肝转移发生的关系。结果:实验组与对照组胃癌组织中HGF呈阳性表达率分别为68%和60%,两组比较差异具有统计学意义。实验组与对照组胃癌组织中c-Met呈阳性表达率分别为86%和68%,两组比较差异具有统计学意义。胃癌患者的淋巴结转移、HGF表达、c-Met表达与胃癌肝转移有关;而浸润深度、分化程度与胃癌肝转移无关。原发癌和肝转移癌HGF表达一致性分析存在显著差异。原发癌和肝转移癌c-Met表达一致性分析无显著差异。结论:HGF和c-Met的高表达与胃癌肝转移机制有关,对于c-Met表达程度的评估可能成为预测胃癌肝转移有价值的预后指标。