SMAD3和CD44在甲状腺乳头状癌组织中的表达水平与临床病理特征及预后的关系

目的探讨信号转导分子3(SMAD3)和白细胞分化抗原44(CD44)在甲状腺乳头状癌(PTC)组织中的表达水平与临床病理特征及预后的关系。方法选取2019年6月-2020年6月收治的PTC患者88例为研究对象,同期取距离癌组织3 cm以上癌旁组织作为对照,实时荧光定量PCR(qRT-PCR)检测SMAD3和CD44的mRNA表达水平;免疫组化法检测SMAD3和CD44的阳性表达情况。Spearman相关性分析PTC患者癌组织中SMAD3和CD44的mRNA表达水平的关系。SMAD3和CD44与PTC患者预后的关系采用Kaplan-Meier法进行分析。COX回归分析影响PTC患者预后的危险因素。结果与癌旁组织相比,PTC组SMAD3的表达水平显著降低(t=8.484,P<0.05),CD44表达水平显著升高(t=11.232,P<0.05)。相关性分析显示,PTC患者癌组织中SMAD3和CD44的mRNA表达水平呈负相关(r s=-0.519,P<0.05)。与癌旁组织相比,PTC组SMAD3阳性表达率显著降低(χ^(2)=41.905,P<0.05),CD44阳性表达率显著升高(χ^(2)=62.888,P<0.05)。SMAD3表达与TNM分期(χ^(2)=7.678,P=0.006)、淋巴结转移(χ^(2)=20.398,P<0.05)、侵犯包膜(χ^(2)=9.881,P=0.002)有关。CD44表达与TNM分期(χ^(2)=3.959,P=0.047)、淋巴结转移(χ^(2)=20.702,P<0.05)、侵犯包膜(χ^(2)=10.363,P=0.001)有关。术后随访3年发现,SMAD3阳性表达PTC患者生存率高于阴性表达患者生存率(χ^(2)=4.644,P=0.031)。CD44阳性表达PTC患者生存率显著低于阴性表达患者生存率(χ^(2)=5.331,P=0.021)。多因素COX回归分析显示,淋巴结转移、SMAD3和CD44表达是影响PTC患者预后的危险因素(P<0.05)。结论PTC组织中SMAD3呈异常低表达,CD44呈高表达,其水平与PTC患者临床病理特征及预后有关。

CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as micro-metastasis

AIM： To detect the expression of CD44 correlated with the ability of micro-metastasis in peripheral blood and bone marrow of patients with gastric cancer and to deduce its clinical significance. METHODS： Preoperative peripheral blood and bone marrow specimens from 46 patients with gastric cancer and 6 controls were studied by semi-quantitative RTPCR amplification of CD44v6mRNA. Preoperative and postoperative peripheral blood specimens from 40 patients with gastric cancer and 14 controls were studied by quantitative RT-PCR amplification of CD44v6mRNA in the corresponding period. RESULTS： Semi-quantitative RT-PCR amplification showed that CD44v6mRNA expression of peripheral blood and bone marrow was positive in 39 （84.8%） and 40 （86.9%） of 46 patients with gastric cancer, respectively. In peripheral blood, CD44v6mRNA expression was positive for diffuse type in 30 （93.8%） of 32 patients and for intestinal type in 9 （64.3%） of 14 patients. On the other hand, in bone marrow, CD44v6mRNA expression was positive for diffuse type in 31 （96.9%） of 32 patients and for intestinal type in 10 （71.4%） of 14 patients. There was a significant difference between the diffuse type and intestinal type. Quantitative RTopCR amplification demonstrated that CD44v6mRNA was not expressed in the peripheral blood of controls and CD44v6mRNA expression was positive for preoperative peripheral blood in 40 patients with gastric cancer, the expression levels being from 4.9 × 10^2 to 3.2× 10^5 copies/g RNA. The average expression level of CD44v6mRNA in peripheral blood was 3.9 × 10^10 copies/g RNA. The expression levels of CD44v6mRNA in peripheral blood in gastric cancer patients after curative operation increased from 5.5 × 100 to 7.6 × 10 copies/g RNA （P = 0.00496）. After curative operation, the expression level decreased markedly. CONCLUSION： Semi-quantitative and quantitative RTPCR amplification for CD44v6mRNA is a sensitive and specific method for the detection of micro-metastasis in peripheral blood and bone marrow, which might be used as an indicator of tumor burden and therapeutic effect.

Expression of CD44v6 gene in normal human peripheral blood

AIM: To investigate if CD44v6 could be used as a molecular marker of cancer progression and metastasis through the detection of CD44v6 gene expression in normal human peripheral blood.METHODS: RNA was extracted from the peripheral blood mononuclear cells of 50 healthy donors, the expression of CD44v6 was investigated using reverse transcriptasepolymerase chain reaction (RT-PCR).RESULTS: CD44v6 mRNA was detected in 58% of healthy volunteers under the proper controls.CONCLUSION: Our results suggest that the measurement of CD44v6 expression in peripheral blood by RT-PCR is not suitable for detection of circulating tumor cells.

EXPRESSION AND CLINICAL SIGNIFICANCE OF CD44 IN THEPERIPHERAL BLOOD OF PATIENTS WITH CASTRIC CANCER

Objective: To investigate the clinical significance of cell adhesive molecule (CD44) expression on periphery blood (PB) of patients with gastric cancer. Methods: Both the level of CD44 and the immunocyte phenotype of the lymphocytes of 110 patients with gastric cancer and 100 healthy subjects were examined by flow cytometry, and the results were analyzed pathologically and statistically. Results: The mean of the CD44% in PB of the healthy subjects was 46.14±3.4 and there were no statistic differences for their age and sex. Site of tumor growth: The significant difference (P<0.01) was present between the patients with the cardiac part (C) or body of gastric (M+C) cancer and normal individuals. The significant difference (P<0.05) was present between patients with the 3 sites involved gastric cancer and normal individuals. Type of tumor mass: The significant difference (P<0.05) was present between patients with mixed type gastric cancer and normal individuals. Size of tumor mass: The significant difference was present between the normal individuals and patients with gastric cancer > 10 cm mass (P<0.01) and 7–10 cm mass (P<0.05). Degree of tumor differentiation: The significant difference (P<0.01) was present between the patients with low differentiation gastric cancer and normal individuals. The significant difference (P<0.01) was present between patients with metastatic stage: The significant difference (P<0.01) was present lymph node gastric cancer and normal individuals. Clinical between the patients with advanced or relapsed gastric cancer and normal individuals. Age: The significant difference (P<0.01) was present between the gastric cancer patients under 59 years and normal individuals. Conclusion: The increased level of CD44 in the PB of patients with gastric cancer indicated the possible existence of relapse, advance or metastasis of tumors. When the tumor was poorly differentiated and bigger in tumor mass, the level of CD44% would be higher. Examining the level of CD44 by flow cytometry in the periphery blood of patients with gastric cancer was useful for the prognosis.

Study of the Peripheral Blood CD44 Expression in the Patients with Non-Small Cell Lung Cancer

Previous study has demonstrated that the peripheral blood CD44 expression level is related with the clinical stage and lymph node metastasis of lung cancer. The present comment was to investigate the relationship between the peripheral blood CD44 expression level and clinic pathological change in 50 patients with non-small cell lung cancer (NSCLC) by flow cytometry method. The results showed that 1) the peripheral blood CD44 expression level in the NSCLC group was higher than that in the benign group (467 ± 15) or the normal group (448 ± 15);2) operation decreased the peripheral blood CD44 expression level in the NSCLC group (533 ± 10 vs. 324 ± 11);3) it also showed same results in NSCLC patients with and without lymph node metastasis (559 ± 12 vs. 477 ± 15) or before and after chemotherapy (550 ± 13 vs. 372 ± 10);4) there were significant differences in the peripheral blood CD44 expression level in non-small cell lung cancer patients of the clinical stage I, II, III and IV (474 ± 14, 526 ± 12, 528 ± 16 and 599 ± 20);And the peripheral blood CD44 expression level was not associated with the clinical pathology parameter including the patient age, gender and tumor size. The data suggested that the peripheral blood CD44 expression level was related with the NSCLC progress, lymphatic metastasis and clinical treatment, and the peripheral blood CD44 expression level as the clinical regular examination should evaluate the progress, lymphatic metastasis and clinical treatment for the patients with NSCLC.

CD_(44)表达与乳腺癌淋巴结转移及预后相关因素的关系

目的：探讨ＣＤ４４表达与乳腺癌淋巴结转移与预后的关系。方法：采用ＬＳＡＢ法对７６例乳腺癌伴淋巴结转移和无转移组ＣＤ４４表达进行了免疫组化检测，并结合临床资料、增殖细胞核抗原（ＰＣＮＡ）、雌激素受体（ＥＲ）表达情况进行综合分析。结果：ＣＤ４４阳性率在乳腺癌伴淋巴结转移组为７０６％，无转移组为４５２％，两组间存在显著性差异（Ｐ＜００５），随着组织学分级的增高ＣＤ４４表达呈递增趋势，Ⅰ级与Ⅱ、Ⅲ级间阳性率差异存在显著性（Ｐ＜００５）；ＣＤ４４与ＰＣＮＡ表达存在平行关系，与ＥＲ表达呈负相关趋势。结论：ＣＤ４４表达与乳腺癌淋巴结转移及预后有关。

CD_(44)在IgA肾病中的表达及临床意义

目的 研究 CD4 4在 Ig A肾病各病变阶段肾组织中的表达及其与临床指标之间的关系 ,探讨 CD4 4在 Ig A肾病发病机理中的生物学意义。方法 应用免疫组织化学 S- P法检测 34例 Ig A肾病肾组织、6例正常肾组织中的 CD4 4的表达情况 ,同时测定 Ig A肾病患者的 2 4小时尿蛋白定量、血压、血肌酐 (Cr)、肌酐清除率 (Ccr)等。分析不同临床分组、病理分级、有无高血压、蛋白尿程度、血 Cr水平等对 CD4 4表达的影响。结果 CD4 4主要于系膜增生、新月体、小管间质炎性细胞浸润的部位表达 ,于细胞性新月体表达最强。整个球性硬化时 ,CD4 4表达近消失。 CD4 4表达与蛋白尿程度正相关 (P<0 .0 5 ) ;与血 cr水平无明显相关性 (P>0 .0 5 ) ;有高血压者 CD4 4表达阳性率 92 % (2 3/ 2 5 ) ,无高血压者为 33.3% (3/ 9) ,两者比较有显著性差异 (P<0 .0 1)。 CD4 4在肾组织中的表达与Ig A肾病患者的年龄、性别无相关性。结论 CD4 4与 Ig A肾病的活动性进展有关 ,CD4 4可作为判定 Ig

CD_(44)V_6和CD_(15s)抗原在子宫内膜癌中的表达及其与临床相关性研究

目的 :探讨CD44V6、CD15s抗原表达与子宫内膜癌和侵袭转移的关系。方法 :应用免疫组化SABC方法对 5 0例子宫内膜癌标本进行CD44V6和CD15s抗原检测。结果 :CD44V6和CD15s在子宫内膜癌中阳性表达率分别为 74 %和 72 % ,两者呈正相关。CD44V6和CD15s表达与子宫内膜癌的临床分期和病理分级呈正相关 ,并随肿瘤细胞侵袭肌层深度的增加 ,阳性表达率增高。结论 :CD44V6、CD15s高表达提示子宫内膜癌生物学行为不良 ,联合检测CD44V6、CD15s可作为判断子宫内膜癌恶性程度、预测转移和评估预后的生物学指标。

胃癌患者外周血CD_(44)v_5含量的测定及临床意义

目的 研究测定胃癌患者外周血淋巴细胞 (PBL)CD4 4变异体 5 (CD4 4v5)含量 ,探讨其对胃癌转移诊断的临床意义。方法 应用流式细胞术 (FCM )检测 30例胃癌患者术前PBLCD4 4v5含量和 10例正常对照组PBLCD4 4v5含量。结果 胃癌患者术前PBLCD4 4v5含量为 7 6 1%± 5 5 4% ,比正常对照组明显增高 (P <0 0 1)。有转移的胃癌患者PBLCD4 4v5含量 (8 77%± 5 95 % )明显高于无转移者 (4 44 %± 2 33% ) ,两者差异显著 (P <0 0 1)。结论 PBLCD4 4v5可望作为胃癌患者转移的生物学监测指标。应用FCM检测胃癌患者术前PBLCD4 4v5含量对胃癌转移的诊断和进展的评价具有重要的临床意义。

Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage,histopathological grade of malignancy and clinical features

AIM:This study was designed to compare the levels of v5 and v6 splice variants of CD44 evaluated using EITSA test in the serum of patients with colorectal cancer in different stages of progression of the disease estimated in pT stage according to WHO score,histopathological grade of malignancy and some clinicopathological features. METHODS:The serum obtained from 114 persons with colorectal adenocarcinomas was examined using ELISA method,pT stage and grade of malignancy of the tumour were examined in formalin fixed and paraffin embedded materials obtained during operation. RESULTS:Only the level of CD44 v5 in the serum of patients before operation with G2 pT4 tumour was lower than that in other probes and the difference was statistically significant. We did not find any other correlations between the level of v5 and v6 CD44 variants and other evaluated parameters. CONCLUSION:The level of CD44 v5 and v6 estimated by ELISA test in the serum can not be used as a prognostic factor in colorectal cancer.

E-cadherin与CD_(44)V_6及nm23蛋白在鼻咽癌中的表达及临床病理学意义

目的 :探讨E cadherin、nm2 3及CD4 4V6 蛋白与鼻咽癌 (NPC)的组织病理 ,转移及预后的关系。方法 :采用Elivision免疫组织化学方法检测其 5 9例鼻咽癌组织中E cadherin、nm2 3及CD4 4V6 基因产物的表达情况 ,分析它们与鼻咽癌患者的病理分型、颈部淋巴结转移情况、分期 ,以及生存期的关系。结果 :E cad蛋白在角化型鳞状细胞癌、分化型非角化性癌和未分化型癌组中的缺失表达率分别为 1/ 7、4 1 8% (14 / 34)、72 2 % (13/ 18) ,P <0 0 5。nm2 3蛋白保留表达组颈部淋巴结转移率为 2 3 8% (5 / 2 1) ,缺失表达组为 86 8% (33/ 38) ,P <0 0 5。其中在Ⅲ期鼻咽癌 (2 5例 )中 ,CD4 4V6 蛋白阳性表达组和阴性表达组 5年生存率分别为 15 4 % (2 / 13)和 6 6 7% (8/ 12 ) ,P <0 0 5 ;nm2 3蛋白保留表达和缺失表达组的 5年生存率分别为 6 / 9和 2 5 0 % (4 / 16 ) ,P <0 0 5。结论 :E cad蛋白表达与鼻咽癌的分化有关 ,nm2 3蛋白表达与鼻咽癌的颈淋巴结转移有关 ;CD4 4V6 蛋白阳性表达及nm2 3蛋白缺失表达是鼻咽癌预后不良的因素。

Construction of cell lines with CD44 cDNA and its application in hepatocellular carcinoma

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组织芯片研究CD_(44)s和CD_(44)V_6在乳腺癌组织中的表达

目的 :研究CD44s和CD44V6的表达与乳腺导管癌分化、浸润及转移的关系。方法 :用组织芯片技术及免疫组织化学方法检测 1 2 0例乳腺导管癌标本和 2 0例正常乳腺标本中CD44s和CD44V6表达情况。结果 :CD44s和CD44V6在乳腺癌组织中表达阳性率分别为 4 6 % (5 5 1 2 0 )和 5 3% (6 4 1 2 0 ) ,在正常乳腺组织中均没有表达 ;CD44V6在低、中分化腺癌中表达阳性率分别为 70 % (2 4 34)和 4 6 % (4 0 86 ) ,差异有显著意义 ,χ2 =5 6 8,P <0 0 5。CD44s和CD44V6表达与乳腺导管癌淋巴结转移明显相关 ,P <0 0 1 ;而且与癌细胞浸润有关 ,P <0 0 1。结论 :CD44s和CD44V6过量表达与乳腺导管癌转移和浸润密切相关 ,联合检测CD44s和CD44V6能更准确地判断乳腺导管癌的转移状态。

CD_(44)V_6和PCNA在食管癌中的表达及相关性研究

目的 :研究CD4 4V6 和PCNA表达与食管癌分级、浸润、转移和预后的关系 ,以及CD4 4V6 表达与PCNA表达的相互关系。方法 :应用微波 SP免疫组化法 ,检测 65例食管鳞状细胞癌组织中CD4 4V6 和PCNA表达水平。结果 :在食管癌中CD4 4V6 和PCNA表达阳性率分别为 5 8 5 %和 69 2 %。CD4 4V6 和PCNA表达均与肿瘤分级、浸润、淋巴结转移和预后相关。CD4 4V6 表达与PCNA表达呈正相关 (r =0 4 5 ,P <0 0 0 5 )。结论 :CD4 4V6 和PCNA是食管癌高度恶性和预后不良的重要生物学指标。食管癌CD4 4V6

大肠癌患者外周血细胞CD_(44)s和CD_(44)V_5及CD_(44)V_6表达的研究

目的 :探讨大肠癌患者外周血细胞CD44s、CD44V5和CD44V6的表达与肿瘤转移和预后的关系。方法 :采用流式细胞术对 6 2例大肠癌患者外周血细胞CD44s、CD44V5和CD44V6的表达率进行检测 ,并分析他们之间的相关性。结果 :大肠癌患者外周血细胞的CD44V5+ 细胞和CD44V6+ 细胞检出率均显著高于正常对照组 ,P <0 0 1;且转移者显著高于未转移者 ,P <0 0 1;而CD44s+ 细胞检出率却显著低于正常对照组 ,P <0 0 5 ;且伴转移者显著低于未转移者 ,P <0 0 1;肿瘤患者外周血细胞CD44V5+ 和CD44V6+ 细胞表达率与CD44s+ 细胞检出率呈显著的负相关 ,r1=0 84 ,P1<0 0 5和r2 =- 0 .87,P2 <0 .0 1。结论 :CD44V5及CD44V6的表达与肿瘤转移密切相关 ,检测大肠癌患者外周血中的CD44s、CD44V及CD44V6的表达可为肿瘤的发生、发展及预后判断提供依据。

CD_(44S)在脑内胶质瘤和转移瘤的表达

目的 探讨 CD4 4S对脑胶质瘤侵袭的影响。 方法 利用免疫组织化学 SP法和半定量方法研究 CD4 4S在脑胶质瘤、脑内转移瘤的表达强度。 结果 CD4 4S在 10例正常人脑组织表达强度为“±”,主要定位在星形细胞膜上 ,在 4 5例脑胶质瘤中显胞膜和 /或细胞质染色 4 3例。 11例脑内转移瘤表达则全部阳性 ,但表达强度均为“+”。高度恶性胶质瘤表达强度较脑内转移瘤和中低度恶性胶质瘤强 ,以“ ”多见 (P<0 .0 1)。 结论 CD4 4S可能与胶质瘤侵袭有关 。

结直肠癌中CD_(44) V_6 PCNA的表达及其与浸润转移的关系

目的 探讨CD44V6和PCNA在结直肠癌中的表达及其与肿瘤浸润转移的关系。方法 应用免疫组织化学S P法检测 87例结直肠癌组织中CD44V6和PCNA的表达情况。结果 87例结直肠癌组织中CD44V6蛋白的表达阳性率为 5 8.6 % ,PCNALI为 5 6 .5 1± 18.82。CD44V6阳性表达率和PCNALI在侵及浆膜层者明显高于侵及肌层者 ,淋巴结转移阳性组高于淋巴结转移阴性组 ,DukesC、D期明显高于A、B期 ,差异均有显著性 (P <0 .0 5 )。PCNA高LI者CD44V6阳性率明显高于PCNA低LI者 ,有显著性差异 (P <0 .0 5 )。结论 CD44V6和PCNA在结直肠癌浸润转移过程中发挥重要作用 ,可作为反映结直肠癌恶性程度的生物学标记物。

大肠癌VEGF和CD_(44)V_6及E-cadherin表达的差异及意义

目的 :探讨大肠癌术前活检、浸润前缘和转移灶癌组织血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)、CD44选择性拼接变异体 6(CD44Variant 6,CD44V6)和E上皮型钙黏附素 (E cadherin)表达的差异以及与大肠癌浸润转移的关系。方法 :检测 94例大肠癌术前活检、浸润前缘癌组织和 48例转移灶癌组织VEGF、CD44V6和E cadherin的表达。结果 :术前活检癌组织VEGF、CD44V6的阳性表达率低于浸润前缘癌组织 ( 4 6 8%、3 8 3 %vs 5 6 4%、48 9% ) ;转移灶癌组织VEGF、CD44V6的阳性表达率与浸润前缘癌组织相近 ( 5 8 3 %、5 0 %vs 5 6 4%、48 9% )。术前活检癌组织VEGF的阳性表达率与大肠癌Duke’s分期、淋巴结转移有关 ;浸润前缘癌组织VEGF的阳性表达率与大肠癌Duke’s分期、浸润深度、淋巴结转移有关。术前活检和浸润前缘癌组织CD44V6的阳性表达率与大肠癌Duke’s分期、浸润深度、淋巴结转移有关。E cadherin在术前活检、浸润前缘和转移灶癌组织中的阳性表达率相近 ( 5 9 6%、5 2 1%和5 8 3 % ) ,E cadherin的表达与大肠癌生物学行为无关。结论 :浸润前缘癌组织和术前活检癌组织VEGF和CD44V6的表达与大肠癌生物学行为有关。VEGF。

结直肠癌中cyclin D1和CD_(44)V_6及E-cadherin蛋白的表达及其意义

目的 :探讨结直肠癌中cyclinD1、CD44V6、E cadherin(E cad)蛋白的表达。方法 :采用免疫组化SP法测定 48例结直肠癌中cyclinD1、CD44V6、E cad蛋白的表达。结果 :48例结直肠癌中cyclinD1、CD44V6、E cad表达的阳性率分别为5 8 3 % ( 2 8/4 8)、75 0 % ( 3 6/4 8)和 45 8%( 2 2 /4 8)。cyclinD1蛋白表达的阳性率 60岁以上年龄组高于 60岁以下年龄组 ,P<0 0 5 ,cyclinD1蛋白的表达与肿瘤组织分化程度呈负相关 ,P <0 0 1。CD44V6高表达及E cad低表达与结直肠癌Duke’s分期、浆膜浸润、淋巴结转移呈正相关 ,P<0 0 5。结论 :cyclinD1蛋白的表达与分化程度相关 ;CD44V6、E Cad蛋白的表达与结直肠癌浸润转移密切相关 ,检测cyclinD1、CD44V6、E cad蛋白是判断结直肠癌预后的客观指标。

宫颈癌CD_(44V6)表达与局部肿瘤血管生成、癌细胞增殖及浸润转移的关系

目的 探讨 CD4 4V6 在宫颈癌中表达与局部肿瘤血管生成、癌细胞增殖及浸润转移的关系。 方法 应用免疫组织化学 SP法检测 15例正常宫颈上皮 (NCE)、18例宫颈上皮内瘤样病变 (CIN)和 75例宫颈癌 (ICC)中CD4 4V6 蛋白、癌细胞增殖指数 (Ki- 6 7标记 )及微血管密度 (MVD,CD34 标记 )的表达情况。 结果 CD4 4V6 在 NCE、CIN和 ICC中的阳性表达率分别为 2 0 .0 0 % ,5 5 .5 6 %和 6 9.33% ,从 NCE到 CIN再到 ICC,CD4 4V6 的阳性表达率显著升高 (P<0 .0 5 )。 CD4 4V6 在宫颈癌中表达与盆腔淋巴结转移、脉管浸润和 Ki- 6 7表达有关 (P<0 .0 5 ) ,而与年龄、FIGO分期、组织学分级、间质浸润和 MVD无关。有淋巴结转移、脉管浸润和 Ki- 6 7高度表达者 CD4 4V6 的阳性表达率显著高于无淋巴结转移、脉管浸润和 Ki- 6 7中度以内表达者。 结论 CD4 4V6 阳性表达可能在宫颈癌发生发展和浸润转移中起重要作用。检测宫颈癌中 CD4 4V6 表达对于了解其生物学行为和判断预后有一定的价值。