UQCRC1 downregulation is correlated with lymph node metastasis and poor prognosis in CRC

BackgroundMitochondrial dysfunction is common in cancer. UQCRC1 is a nuclear-encoded protein localized to the inner mitochondrial membrane; however, little is known about it in colorectal cancer (CRC). The purpose of this study was to investigate the expression pattern and the possible clinical significance of UQCRC1 in CRC.MethodsA total of 197 patients with CRC were enrolled in this study. Immunohistochemistry was used to evaluate the expression pattern of UQCRC1. The relationship between UQCRC1 and clinical characteristics, especially lymph node metastasis, was also assessed. In addition, we evaluated the significance of UQCRC1 in the prognosis for CRC patients.ResultsUQCRC1 was downregulated in 28.9% (57/197) of human CRCs. Downregulation of UQCRC1 was correlated with increased lymph node metastasis (p < 0.001) and decreased disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that downregulation of UQCRC1 was an independent prognostic factor both for DFS (HR 3.009; 95% CI: 1.613–8.548, P = 0.009) and OS (HR 4.062; 95% CI: 2.835–8.910, P = 0.001). In addition, downregulation of UQCRC1 was correlated with increased VEGF-C expression (P = 0.002).ConclusionUQCRC1 was downregulated in human CRC. Downregulation of UQCRC1 was correlated with increased lymph node metastasis and finally associated with decreased survival in CRC.     

口腔颌面部淋巴管畸形的VEGF-C和VEGFR-3表达

目的 :观察接受和未接受平阳霉素治疗的淋巴管畸形中VEGF -C和VEGFR - 3表达 ,探讨平阳霉素治疗淋巴管畸形机制。方法 :收集 2 0例接受平阳霉素治疗的淋巴管畸形标本及 10例未接受治疗的标本做组织学观察以及免疫组织化学研究 ,评价形态学变化并分析VEGF -C和VEGFR - 3表达是否存在差异。结果 :两组病变VEGF -C和VEGFR - 3表达有显著性差异 (P <0 .0 5 ) ,并且VEGF -C和VEGFR - 3表达有相关性。结论 :平阳霉素注射治疗淋巴管畸形的分子机制可能是通过抑制VEGF -C -VEGFR - 3系统的信号传导从而达到治疗淋巴管畸形的目的     

VEGF-C及受体mRNA的表达与口腔鳞癌淋巴管生成的关系

目的探讨VEGF-C及受体在口腔鳞癌淋巴管生成中的作用。方法采用RT-PCR方法,检测47例口腔鳞癌组织标本、15例正常口腔黏膜VEGF-C、flt-4的表达;应用酶组织化学方法检测癌周微淋巴管密度(MLVD)。结果口腔鳞癌VEGF-C、flt-4mRNA的表达率分别为57.4%、61.7%,显著高于正常对照组的20%、20%(P<0.025);口腔鳞癌MLVD为14.04±6.92,显著高于正常对照组的5.48±2.62(P<0.001);VEGF-C、flt-4阳性组中,MLVD分别为17.38±4.90和17.34±4.69,显著高于阴性组的9.54±3.79和8.72±2.99(P<0.001),且VEGF-C、flt-4mRNA的表达具有显著相关性。结论VEGF-C、flt-4在口腔鳞癌癌周淋巴管生成中具有重要作用。     

miR-377-5p通过下调VEGF-C对结肠癌的血管和淋巴管生成的影响研究

目的探讨miR-377-5p通过下调VEGF-C对结肠癌的血管和淋巴管生成的影响研究。方法该实验分为3组,miR-377-5p干扰组、miR-377-5p阴性对照组和miR-377-5p过表达组。采用实时荧光RT-PCR、Western blot、CCK-8、流式细胞、细胞划痕、Transwell、血管生成实验检测miR-377-5p m RNA和蛋白表达、细胞增殖、凋亡、迁移、侵袭、血管和淋巴管生成。结果与正常结肠组织对比,结肠癌组织中miR-377-5p m RNA和miR-377-5p蛋白的表达明显低于正常结肠组织(均P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组中的m RNA及蛋白显著升高(均P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的m RNA及蛋白明显增加(P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组的结肠癌细胞增殖能力明显降低(P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的结肠癌细胞增殖能力显著降低(P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组的结肠癌细胞增殖凋亡明显升高(P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的结肠癌细胞凋亡能力显著升高(P<0.05);伤口愈合实验显示,miR-377-5p过表达组的结肠癌细胞的迁移能力显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05);miR-377-5p过表达组的结肠癌细胞的侵袭能力也明显低于miR-377-5p干扰组和miR-377-5p阴性对照组(P <0.05);miR-377-5p过表达组的VEGF-A、VEGF-C和P-Akt、VEGFR-3蛋白水平显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05);miR-377-5p过表达组的MVD(微血管密度)和LMVD(淋巴微血管密度)显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05)。结论 miR-377-5p在结肠癌中低表达,抑制了结肠癌细胞的增殖、细胞迁移和侵袭,促进了结肠癌细胞的凋亡能力,并直接靶向VEGF-C抑制肿瘤的血管和淋巴管生成。     

肝细胞生长因子对人舌鳞癌 Tca8113细胞 VEGF-C 表达的影响及作用机制的初步研究

目的：研究 HGF 对人舌鳞癌 Tca8113细胞中 VEGF-C 表达的影响并探讨其作用机制。方法：体外培养 Tca8113细胞,应用 ELISA 方法测定不同浓度 HGF 作用下以及分别用 LY294002、U0126、SP600125、SB203580信号通路抑制剂阻断PI3K/Akt、P44/P22MAPK、JNK、P38MAPK 信号通路后 VEGF-C 的表达水平。结果：随着培养液中 HGF 浓度的增加,Tca8113细胞中 VEGF-C 的表达水平出现先增高后降低的趋势,当 HGF 浓度为40 ng/ml 时,VEGF-C 表达水平最高。PI3K/Akt 信号通路抑制剂（LY294002）和 P42/44MAPK 信号通路抑制剂（U0126）显著抑制了 HGF 刺激下 Tca8113的 VEGF-C 蛋白的表达（P ＜0．01）;而 JNK 信号通路抑制剂（SP600125）和 P38MAPK 信号通路抑制剂（SB203580）对 HGF 刺激下 Tca8113的 VEGF-C 蛋白的表达影响甚微（P ＞0．05）。结论：在人舌鳞癌 Tca8113细胞中,随着 HGF 浓度的增加,VEGF-C 的表达先增高后降低。PI3K/Akt 和 P44/P22MAPK 信号通路在口腔鳞状细胞癌淋巴转移中可能发挥作用。     

子宫内膜癌中VEGF-C及其受体mRNA的表达及临床意义

目的 研究子宫内膜癌组织中血管内皮生长因子C及其受体mRNA的表达情况,分析其在肿瘤转移中的作用.方法 采用RT-PCR法分析48例新鲜子宫内膜癌组织标本中VEGF-C/KDR/Flt-4mRNA的表达情况,并分析其与各临床病理参数之间的关系.结果 48例子宫内膜癌组织中的VEGF-C及其受体mRNA表达率明显高于正常子宫内膜组织,肿瘤组织中VEGF-CmRNA表达与Flt-4mRNA的表达呈显著正相关.结论 VEGF-C可能在子宫内膜癌转移尤其是淋巴转移中起重要作用,是一个反映病人淋巴转移和预后的良好指标.     

血管内皮生长因子C及其受体与宫颈癌临床和预后的关系

目的:观察血管内皮生长因子C(VEGF-C)与血管内皮生长因子受体3(VEGFR-3)在宫颈癌组织中的表达并分析其与临床及预后的关系。方法:免疫组织化学SP法检测80例宫颈癌组织中VEGF-C与VEGFR-3的表达,以30例正常宫颈组织为对照组。结果:VEGF-C在癌组织中呈高表达,癌周组织表达相对较低,但两组表达均高于对照组(P<0.05);癌组织中VEGF-C的表达与肿瘤的临床分期相关,淋巴结转移组VEGF-C的阳性表达率为69.6%明显高于无淋巴结转移组的49.1%,差异有统计学意义(P<0.05)。VEGFR-3在癌周组织表达较高,癌组织中表达较低,但都明显高于对照组(P<0.05);淋巴结转移组中的VEGFR-3在癌周组织标记的淋巴管密度为19.67±3.72明显高于无淋巴结转移组10.78±2.65,差异有统计学意义(P<0.05);Ⅰb期组VEGFR-3的表达15.78±5.67明显高于Ⅰa2期9.87±1.95,低于Ⅱa期18.78±4.32,随着宫颈癌临床分期及病理组织学分级的提高,VEGFR-3表达也随之增强,差异有统计学意义(P<0.05)。结论:VEGF-C和VEGFR-3与宫颈癌的发生发展密切相关,癌组织VEGF-C和癌周组织VEGFR-3表达水平的检测可能有利于临床评估宫颈癌的预后。     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

胰岛素样生长因子1受体和血管内皮生长因子C表达及其与宫颈癌淋巴结转移的关系

目的 研究宫颈癌中胰岛素样生长因子1受体(IGF-1R)和血管内皮生长因子C（VEGF-C）的表达及其与淋巴结转移关系。方法 选取河南科技大学第一附属医院2008年9月至2011年5月50例宫颈鳞癌组织为研究组，30例正常宫颈组织为对照组，应用SP免疫组化法研究IGF-1R、VEGF-C的表达情况。结果 研究组淋巴结转移与IGF-1R、VEGF-C阳性表达有关(P< 0.05)。D2-40标记的淋巴管密度（LVD）在IGF-1R、VEGF-C阳性表达组明显高于阴性组，且两者的阳性表达在研究组呈正相关。结论 IGF-1R、VEGF-C的表达与宫颈癌的淋巴转移有关，对于早期判断淋巴结转移有一定价值，联合检测二者有助于判断预后，指导临床治疗。     

宫颈癌中iNOS的表达与肿瘤新生淋巴管及VEGF-C的关系

目的:探测人宫颈癌中的诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、血管内皮生长因子-C(vascular endothelial growth factor,VEGF-C)的表达与D2-40标记的淋巴管密度的关系.方法:采用免疫组化SP法检测宫颈鳞状细胞癌中iNOS、VEGF-C的表达情况,并用D2-40进行癌组织淋巴管染色,测定其淋巴管密度(lymphatic vessel density,LVD),另取正常宫颈组织10例作对照,观察上述因子在宫颈癌及正常宫颈中的表达及其与肿瘤病理参数之间的相关性.结果:与正常宫颈组织相比,宫颈癌组织中具有更高的iNOS、VEGF-C的表达率及淋巴管密度(t=2.39、3.08,P=0.021、0.003).与无淋巴结转移组相比,淋巴结转移组具有更高的iNOS、VEGF-C阳性表达率(P =0.044、0.035)及淋巴管密度(t=3.79,P＜0.001);iNOS、VEGF-C阳性共表达与肿瘤淋巴结转移之间存在正相关(P=0.046),宫颈癌组织中iNOS、VEGF-C的表达具有相关性(P＜0.001).结论:iNOS、VEGF-C在宫颈癌组织中呈过表达,其与宫颈癌的淋巴转移关系密切;iNOS可能通过催化产生NO上调VEGF-C的表达,诱导肿瘤淋巴管生成,导致宫颈癌的淋巴道转移.iNOS、VEGF-C均参与宫颈的发展、浸润和转移,可作为评估宫颈癌的生物学行为和判断预后的指标.针对iNOS、VEGF-C的靶向治疗可成为宫颈癌治疗的新靶点.