乳腺癌患者血清中sCD44v6检测的临床意义

目的：探讨乳腺癌患者血清中可溶性CD44v6（sCD44v6）蛋白的含量及其临床意义。方法：采用酶联免疫吸附实验（ELISA）检测48例乳腺癌患者手术前后及10例健康对照组血清中sCD44v6蛋白的含量。结果：48例乳腺癌患者血清中sCD44v6蛋白的含量为（546.45±63.79）ng/ml,显著高于健康对照组（167.32±50.06ng/ml,P〈0.01。乳腺癌患者行根治性手术后sCD44 v6蛋白的含量明显下降,有统计学意义,P〈0.05。并与淋巴结转移、组织学分级、TNM分期及低龄（≤35岁）密切相关。结论：sCD44v6水平可作为诊断、治疗乳腺癌及预测乳腺癌患者转移复发风险及预后的辅助指标。     

非小细胞肺癌患者血清sCD44v6检测的临床意义

目的:探讨检测血清sCD44v6在非小细胞肺癌(NSCLC)诊断中的价值. 方法: 以酶联免疫吸附测定(ELISA)法检测50例NSCLC患者血清中sCD44v6的浓度,观察其与NSCLC的诊断、预后的相关性.结果: 肺鳞癌组 sCD44v6的水平[(307.47±79.00)ng/ml],肺腺癌组sCD44v6水平[(369.53±114.19)ng/ml],明显高于正常对照组[(95.60±17.50)ng/ml],差异有显著性P<0.001,NSCLC Ⅲ Ⅳ期患者sCD44v6的水平[(412.60±68.02) ng/ml]明显高于正常对照组[(95.60±17.50)ng/ml], 差异有显著性P<0.001;结论: sCD44v6水平与NSCLC及其转移有明显关联,可作为判断NSCLC组织类型和分期的辅助指标,对早期诊断的价值不大.     

血清CD44v6表达在结直肠癌中的临床应用价值

目的 探讨血清可溶性细胞表面黏附分子sCD44v6在结、直肠癌中的临床应用价值.方法 96例不同Duke分期结、直肠癌患者和24例健康者,分别采用酶联免疫吸附法(ELISA)定量检测其血清sCD44v浓度,化学发光免疫法检测血清CEA浓度;并结合临床资料进行分析.结果 结、直肠癌患者sCD44v6浓度为275.3±115.8 ng/ml,明显高于健康对照组(61.3±7.8 ng/ml)(P＜0.05),若以健康对照组的(-x)+2s(76.9 ng/ml)作为正常上限值,其阳性率为73.96%;sCD44v6水平随癌肿Duke分期的升级和肿瘤细胞的转移而呈现递增趋势,各组之间比较差异有统计学意义(P＜0.05).与CEA相比,sCD44v6水平在反映癌组织浸润和转移程度上更直接、敏感.结论 结、直肠癌患者sCD44v6水平和阳性率均显著增高,并与肿瘤的分期和扩散转移程度密切相关;术前sCD44v6水平检测可作为结、直肠癌患者病程和转移预测的一个重要指标.     

腹水中TB-AB、ADA和sCD44v6的检测及意义

目的:探讨可溶性CD44v6(sCD44v6)、腺苷脱氨酶(adenosine deaminase,ADA)和结核抗体(mycobac-terium tuberculosis antibody,TB-AB)联合检测对良、恶性腹水的鉴别诊断价值。方法:取48份结核性腹水、39份恶性腹水,分别用酶联免疫吸附试验(ELISA)、酶速率法及胶体金标法检测腹水sCD44v6、ADA及TB-AB水平。结果:恶性腹水组sCD44v6水平为(102.2±30.6)ng/ml,明显高于结核性腹水组(43.5±15.3)ng/ml(P<0.01);结核性腹水组ADA水平为(55.3±22.4)U/L,明显高于恶性腹水组(21.6±12.7)U/L(P<0.01)。结核患者血清ADA水平为(44.5±17.1)U/L,明显高于恶性肿瘤患者血清ADA水平(25.6±13.8)U/L(P<0.01)。以60.5ng/ml为阳性界值,sCD44 v6诊断恶性腹水的敏感度为82.1%、特异度为87.5%。以45U/L为阳性界值,ADA诊断结核性腹水的敏感度为83.3%、特异度为87.2%。以腹水/血清ADA比值>1.0为阳性界值,诊断结核性腹水的敏感度、特异度分别为89.6%、92.3%。TB-AB诊断结核的敏感度及特异度分别为85.4%及87.2%,诊断恶性肿瘤的敏感度为5.1%。TB-AB、ADA及P-ADA/S-ADA联合检测,诊断结核性腹水的敏感度、特异度分别为95.8%、94.9%。结论:TB-AB、ADA和sCD44v6对于良、恶性腹水的鉴别诊断有重要价值。     

非小细胞肺癌患者血清sCD44v6检测的临床意义

目的：探讨检测血清sCD44v6在非小细胞肺癌（NSCLC）诊断中的价值。方法：以酶联免疫吸附测定（ELISA）法检测50例NSCLC患者血清中sCD44v6的浓度，观察其与NSCLC的诊断、预后的相关性。结果：肺鳞癌组sCD44v6的水平[（307．47±79．00）ng／ml]，肺腺癌组sCD44v6水平[（369．53±114．19）ng／m1]，明显高于正常对照组[（95．60±17．50）ng／m1]，差异有显著性P〈0．001，NSCLCⅢ＋Ⅳ期患者sCD44v6的水平[（412．60±68．02）ng／m1]明显高于正常对照组[（95．60±17．50）ng／ml]，差异有显著性P〈0．001；结论：sCD44v6水平与NSCLC及其转移有明显关联，可作为判断NSCLC组织类型和分期的辅助指标，对早期诊断的价值不大。     

血清sCD44v6检测在肺癌中的临床意义

 目的 探讨血清可溶性CD44v6（sCD44v6）检测在肺癌的诊断和治疗中的临床意义。方法 对75例肺癌患者和30名正常健康者（正常组）的血清标本，采用ELISA定量法检测sCD44v6含量。结果 肺癌患者血清sCD44v6含量为（314.77±84.83）ng／ml，显著高于正常组（101.10±9.18）ng／ml（P＜0.000）。肺癌患者根治术后血清sCD44v6较术前明显下降（P＜0.000）；化疗后血清sCD44v6较化疗前明显下降（P＜0.000）。早期（Ⅰ期＋Ⅱ期）肺癌患者血清sCD44v6显著低于晚期（Ⅲ期＋Ⅳ期）患者（P＜0.01）。不同组织类型的肺癌患者血清sCD44v6含量差异无统计学意义（P＞0.05）。结论 血清sCD44v6检测在肺癌的辅助诊断、手术疗效和化疗疗效以及预后判断方面具有重要价值     

乳腺癌患者血清Her-2/neu蛋白的临床意义

[目的]探讨血清Her-2/neu蛋白在乳腺癌患者诊疗中的临床意义.[方法]应用化学发光法(chemiluminescence immunoassay,CLIA)对60例健康人、100例其他肿瘤患者和195例乳腺癌患者样本进行Her-2/neu蛋白检测.[结果]健康对照组、其他肿瘤对照组和乳腺癌组血清Her-2/neu浓度分别为10.3± 1.7ng/ml、10.9±2.6ng/ml和23.7±38.8ng/ml,乳腺癌组浓度明显高于健康对照组(P=0.003)和其他肿瘤组(P=0.005).Ⅰ～Ⅱ期乳腺癌血清Her-2/neu浓度明显低于Ⅲ～Ⅳ期,差异有统计学意义(P=0.001).乳腺癌Her-2阴性、+、++和+++4组患者血清Her-2/neu蛋白浓度分别为32.3±56.2ng/ml、27.9±31.4ng/ml、17.7±29.2ng/ml和23.1 ±39.6ng/ml;血清Her-2/neu蛋白阳性率分别为26.67％ 、33.33％、11.11％和15.38％.转移性乳腺癌患者血清Her-2/neu检测结果与临床状态总体符合率为82.98％(39/47).[结论]血清Her-2/neu蛋白水平与乳腺癌患者临床分期相关,化学发光法检测血清Her-2/neu蛋白在乳腺癌临床诊疗中有重要应用价值.     

血清肝细胞生长因子水平与乳腺癌转移的关系

目的:研究血清肝细胞生长因子(hepatocytegrowthfactory,HGF)与乳腺癌转移的关系。方法:应用双抗体夹心ELISA方法检测80例术后复发转移乳腺癌患者,50例术后无复发乳腺癌患者和20例献血员的血清肝细胞生长因子水平。结果:术后复发转移组血清HGF水平(0.90±0.52ng/ml)显著高于无复发组(0.38±0.30ng/ml;P<0.01)和正常对照组(0.22±0.36ng/ml;P<0.01)。肝转移组患者血清HGF水平(1.25±0.57ng/ml)显著高于其它转移组(0.78±0.48ng/ml;P<0.01)。多处转移组血清HGF水平(1.10±0.66ng/ml)显著高于其它转移组(0.78±0.48ng/ml;P<0.05)。结论:血清HGF水平与乳腺癌肝转移和多处转移发生密切相关。     

结直肠癌患者血清VEGF和sCD44v6检测的意义

[目的]研究结直肠癌患者血清中VEGF和sCD44v6的水平和临床意义.[方法]应用EILSA法检测比较106例结直肠癌患者和32例正常人血清中VEGF和sCD44v6的水平.[结果]大肠癌患者血清中VEGF和sCD44v6水平均高于正常对照组,且与肿瘤的分期、转移和浸润程度相关(P＜0.01).但与癌细胞分化程度无明显相关(P＞0.05).[结论]血清中VEGF和sCD44v6是观察大肠癌病程进展及肿瘤浸润和转移的较好的指标.     

CD44v6与可溶性CD44v6在胃癌中的表达及与预后的关系

目的 探讨CD44v6与可溶性CD44v6(sCD44v6)在胃癌中的表达及与胃癌生物学行为和预后的关系.方法 应用免疫组化S-P法检测103例胃癌组织和10例正常胃黏膜标本的CD44v6表达,并对患者进行术后随访,随访期为3～91个月;应用酶联免疫吸附(ELISA)法检测86例胃癌、30例胃溃疡患者和30例健康人外周血血清中sCD44v6的浓度,并对患者进行术后随访,随访期为1～91个月.结果 (1)CD44v6在正常胃黏膜中不表达,而在胃癌中的表达率为60.2%;CD44v6的表达与淋巴结转移、TNM分期、脉管是否存在癌栓以及Borrmann分型有关(P＜0.05),而与胃癌浸润深度、是否远处转移、分化程度以及患者的生存率无关(P＞0.05);9例伴有肝转移的胃癌患者中,有7例CD44v6为强阳性表达.(2)胃癌患者外周血血清中sCD44v6的浓度明显高于胃溃疡组和健康对照组(P＜0.01);胃癌根治术后患者血液中sCD44v6的浓度比术前明显下降(P＜0.01),而姑息术后患者的浓度变化却不明显(P＞0.05);sCD44v6的浓度与胃癌浸润深度、淋巴结转移、是否远处转移、脉管是否存在癌栓、Borrmann分型以及分化程度无关;sCD44v6浓度较高组的生存率较sCD44v6浓度较低组高,且差异有统计学意义(P=0.0281),但经Cox回归分析显示,sCD44v6的浓度与生存期有关(P=0.415),而手术方式却与生存期有关(P=0.000).(3)胃癌组织中CD44v6的表达与外周血血清中sCD44v6的表达无明显平行关系(P＞0.05).结论 CD44v6的表达对评估胃癌生物学行为有参考价值,但是否与预后有关仍需探讨;sCD44v6的表达对胃癌辅助诊断、手术彻底性判定及生物学行为评估有一定的意义;CD44v6与sCD44v6的表达无明显平行关系.     

不能手术的非小细胞肺癌同步放化疗对血清CD44v6 和VEGF表达水平的影响及其临床意义*

目的:检测不能手术的非小细胞肺癌（NSCLC ）患者同步放化疗前、后血清CD44v6 和VEGF（sCD 44v6,sVEGF ）表达水平,探讨其动态变化规律与不能手术NSCLC 病理生理特征、疗效及预后的相关性。方法:采用生物素- 亲和素系统ELISA 双抗体夹心法定量检测50例不能手术NSCLC 患者同步放化疗前、后血清CD44v6 和VEGF的表达水平。结果:1）治疗前CD44v6 水平（570.89± 63.30）ng/L 和VEGF水平（241.09± 85.96）ng/L 均显著高于对照组（356.32± 97.68）ng/L（P<0.01）与（103.72± 39.22）ng/L（P<0.05）。 2）治疗前VEGF表达水平与原发肿瘤大小、远处转移、细胞分化及临床分期等有显著相关性（P<0.05）,与原发部位、淋巴结转移和组织学类型等无明显相关性（P>0.05）。 而CD44v6 表达水平与原发肿瘤大小、远处转移、细胞分化、临床分期、淋巴结转移及组织学类型等有显著相关性（P<0.05）,与原发部位、性别和年龄无明显相关性（P>0.05）。 3）治疗前CD44v6 水平（570.89±63.30）ng/L 和VEGF 水平（241.09± 85.96）ng/L 均分别高于治疗后的水平（281.44± 74.28）ng/L（P<0.01）和（133.64± 67.69）ng/L（P<0.01）。 4）治疗后CD44v6 和VEGF平均水平与治疗前比较,CR组显著降低（P<0.01）,PD组降低不明显（P>0.05）,而PR组和SD组降低介于两者之间（P<0.05）。 5）治疗前、后CD44v6 和VEGF 水平呈正相关（r=0.291,P<0.05）。 结论:同步放化疗前后CD44v6/VEGF水平与不能手术NSCLC 的多项临床病理特征密切相关。它们的水平变化是预测不能手术NSCLC 生物学行为的有用指标,可为临床判断疗效及预后提供依据。      

Soluble CD44 v5 and v6 in serum of patients with breast cancer. Correlation with expression of CD44 v5 and v6 variants in primary tumors and location of distant metastasis

Primary breast cancers were shown to overexpress CD44 v5 and v6 at the plasma membrane. However, the clinical significance of this overexpression remains unclear. Overexpression of CD44 v5 and v6 in primary breast cancers was found to correlate with metastasis and poor prognosis by some investigators, yet this correlation could not be confirmed by others using different antibodies. In this study the influence of metastatic disease, the site of metastasis, and the amount of CD44 v5 and v6 expression in the primary tumor on serum levels of the soluble forms of CD44 v5 and v6 (sCD44 v5 and v6) in breast cancer patients was investigated. Soluble CD44 v5 and v6 serum levels were measured by enzyme linked immuno sorbent assay in a group of breast cancer patients who developed metastases in various organs and in another group of patients with single organ metastasis. For control, sCD44 v5 and v6 levels were measured in breast cancer patients who remained free of metastasis and in healthy blood donors. Expression of plasma membrane bound CD44 v5 and v6 in the primary tumors of the patients with metastasis in various organs was correlated to sCD44 v5 and v6 levels in serum. Furthermore the size of sCD44 v6 was analyzed by immunoblot using a monoclonal antibody directed against CD44 v6. When metastases were detected, sCD44 v5 and v6 serum levels were increased as compared to levels measured one month after tumor surgery in patients free of metastases (p = 0.0025 and p = 0.0004). Six of 19 and 6 of 20 patients had sCD44 v5 and v6 serum levels above a cut-off level of 85 and 275 ng/mL, respectively. In these cases expression of CD44 v5 and v6 in the primary cancers was also elevated. Low sCD44 v5 and v6 serum levels were associated with weak expression of CD44 v5 and v6 in the respective primary cancers. As shown by statistical analysis of sCD44 v5 and v6 levels in 57 patients with single organ metastases, elevated sCD44 v6 levels but not sCD44 v5 levels were associated with metastases in liver or bone (p = 0.0025). Immunoblot analysis of soluble CD44 proteins in serum revealed two CD44 v6 specific signals of approximately 120 and 170 kDa. Increased sCD44 v5 and v6 serum levels in patients with breast cancer were influenced by the amount of CD44 v5 and v6 expression in the primary tumor by the site of metastasis. Elevated sCD44 v6 serum levels were preferentially found in patients with metastases in liver or bone.     

Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer

The expression of CD44v6 is well known as a useful marker of tumor progression and prognosis in colorectal cancer. In this study, we evaluated the serum levels of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the histological expression of CD44v6 in patients with colorectal cancer. Serum samples were obtained from 44 primary colorectal cancer patients before surgery. We used enzyme-linked immunosorbent assay to determine the serum levels of sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of the primary tumors obtained from the same patients. Both the serum concentration of sCD44v6 and the expression of CD44v6 were significantly associated with lymph node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in those patients with CD44v6-positive tumor tissues (154.4 +/- 34.8 ng/ml) than in those with CD44v6-negative ones (130.7 +/- 32.3 ng/ml; p < 0.05). The 5-year survival rate was significantly lower in patients with high serum levels of sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and it was also significantly lower in patients with CD44v6-positive cancer (42.1%) than in those with CD44v6-negative cancer (84%; p < 0. 01). We concluded that preoperative elevation in the serum levels of sCD44v6 might be a prognostic indicator for patients with colorectal cancer.     

Serological Evaluation of Soluble CD44 in Renal Cancer

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme-linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico-pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745±170 ng/ml vs. 563±159 ng/ml, P =0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287±121 vs. 220±59, P =0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico-pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth-type cancers than in the slow growth-type cancers (3.95±2.12 vs. 2.63±0.82, P =0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth-type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth-type cancers.     

Soluble CD44 splice variants in metastasizing human breast cancer

The local expression of CD44 splice variants in human breast cancer tissue has been previously shown to be associated with metastasis. We show here that elevated systemic serum levels of CD44 splice variants occur in breast cancer and may represent a new tool for staging and differential diagnosis. Sera of node-negative and node-positive breast cancer patients in comparison with healthy control subjects were analyzed for serum CD44 (sCD44) and 2 different splice variants (v5 and v6). Node-positive breast cancer patients showed significantly (p < 0.01) elevated levels of sCD44-v5 and -v6 splice variants in comparison to node-negative patients and healthy controls. None of the node-negative breast cancer patients or healthy controls showed elevated levels of both sCD44-v5 and -v6. Interestingly, no differences were seen for serum levels of non-spliced sCD44-standard between the 3 groups. Soluble forms of CD44 variants may promote migration of tumor cells. This may occur through interference with tumor cell adhesion or by modulation of immune defense mechanisms. Int. J. Cancer 74:443–445, 1997. © 1997 Wiley-Liss, Inc.     

Evaluation of soluble CD44 in patients with breast and colorectal carcinomas and non-Hodgkin's lymphoma.

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.