胃癌组织Skp2表达的意义及与p27表达的关系

目的探讨人胃癌S期激酶相关蛋白2(S-phase k inase-assoc iated prote in 2,Skp2)表达的意义及与p27表达的关系。方法采用免疫组化方法检测138例原发性胃癌,配对癌旁胃黏膜,102例配对淋巴结转移胃癌组织,30例非典型增生,30例肠上皮化生(肠化),10例慢性浅表性胃炎和5例正常胃黏膜Skp2的表达及138例原发性胃癌p27的表达。结果Skp2表达的阳性率(%),肠化(12.68±0.86)及癌旁胃黏膜(19.32±1.22)均明显高于慢性浅表性胃炎(0.53±0.13)及正常胃黏膜(0.47±0.19)(P=0.000),后两者差异无显著性(P=0.716);非典型增生(16.74±0.82)明显高于肠化(P=0.000);原发性胃癌(31.34±2.17)明显高于非典型增生及癌旁胃黏膜(P值均=0.000);淋巴结转移胃癌组织(39.76±2.00)明显高于原发性胃癌(P=0.037)。胃癌Skp2的阳性率与分化程度(rho=0.315,P=0.000)、脉管内瘤栓(rho=0.303,P=0.000)及淋巴结转移(rho=0.254,P=0.000)呈正相关。胃癌Skp2表达与靶蛋白p27表达呈负相关(rho=-0.451,P=0.000)。结论Skp2蛋白过表达与胃癌的发生及转移有关;胃癌Skp2蛋白过表达与p27蛋白降解有关,提示Skp2蛋白过表达在胃癌发生、发展过程中可能起重要作用。     

前列腺癌中泛素降解途径蛋白的表达及与临床病理特征的相关性

目的 探讨泛素降解途径蛋白Skp2、p27kipl和PTEN在前列腺癌中的表达及与前列腺癌各项临床病理特征的关系,并探讨三者的相关性.方法 应用免疫组织化学法和图像分析系统研究41例前列腺癌标本、20例开放手术切除良性前列腺增生标本中Skp2、p27kipl和PTEN的表达情况.并使用Mann-Whitney检验、Spearman等级相关分析临床病理资料与免疫组化的结果及Skp2、p27kipl和PTEN之间的相关性.结果 在前列腺癌中,Skp2蛋白染色阳性率显著高于良性前列腺增生(P<0.001),p27kipl蛋白染色阳性率显著低于良性前列腺增生(P<0.001),PTEN蛋白染色阳性率显著低于良性前列腺增生(P<0.001).Skp2 蛋白表达与前列腺癌术前PSA水平、肿瘤穿透前列腺被膜、肿瘤分期、病理分级密切相关(P<0.05).而p27kipl和PTEN蛋白表达与上述临床病理特征负相关(P<0.05).Spearman 等级相关分析表明,Skp2与p27kipl蛋白表达呈负相关(r=-0.572, P<0.001),Skp2与PTEN 蛋白表达呈负相关(r=-0.433, P=0.005).结论 Skp2蛋白在前列腺癌中表达增加,与术前PSA水平、局部浸润、临床分期和病理分级呈正相关,而p27蛋白在前列腺癌中表达降低,与上述临床病理特征呈负相关,Skp2蛋白表达与p27蛋白表达之间呈负相关.Skp2表达与抑癌基因PTEN蛋白表达呈负相关.     

喉鳞状细胞癌中Skp2、PTEN及p27蛋白的表达及其意义

目的探讨Skp2、PTEN及p27蛋白表达与喉鳞状细胞癌(LSCC)发生、发展的关系。方法采用免疫组化SABC法检测65例LSCC组织中Skp2、PTEN及p27蛋白的表达情况。结果Skp2、PTEN及p27蛋白在LSCC组织中总的阳性表达率分别为60.0%,49.2%和41.5%,Skp2过表达与LSCC的临床分期及淋巴结转移正相关(P均<0.05),低分化、伴颈部淋巴结转移及Ⅲ～Ⅳ期LSCC组织中PTEN阳性率明显降低(P均<0.05),p27在颈部淋巴结转移组中阳性率显著降低(P<0.05)。结论联合检测Skp2、PTEN及p27的表达有助于综合评估LSCC的生物学行为。     

Skp2和P27kip1在前列腺癌组织中的表达与临床病理特征的相关性研究

背景及目的:F-box蛋白Skp2参与细胞周期抑制蛋白P27kip1泛素化降解,研究发现Skp2在乳腺癌、胃癌、前列腺癌等多种恶性肿瘤中表达增加.本研究旨在探讨Skp2和P27kip1在前列腺癌组织中的表达及与前列腺癌各项临床病理特征的关系,并探讨两者的相关性.方法:用免疫组化EnVisionTM方法检测Skp2和P27 kip1蛋白在41例前列腺癌和20例良性前列腺增生组织中的表达情况.结果:在前列腺癌中的Skp2蛋白阳性率[(8.52±2.40)%]显著高于良性前列腺增生[(0.21±0.15)%](P＜0.001).Skp2蛋白表达与前列腺癌术前血清前列腺特异性抗原(PSA)水平(r=0.360,P=0.021)、局部浸润(r=0.570,P＜0.001)、肿瘤分期(r=0.531,P＜0.001)、病理分级(r=0.514,P=0.001)呈正相关.在前列腺癌中的P27kip1蛋白阳性率[(70.71±4.25)%]显著低于良性前列腺增生[(97.21±2.10)%](P＜0.001).P27kip1蛋白表达与前列腺癌术前PSA水平(r=-0.399,P=0.010)、局部浸润(r=-0.329,P=0.036)、肿瘤分期(r=-0.453,P=0.003)、病理分级(r=-0.290,P=0.046)呈负相关.前列腺癌中P27kip1蛋白与Skp2表达呈负相关(r=-0.572,P＜0.001).结论:前列腺癌中Skp2蛋白表达与靶蛋白P27 kip1蛋白降解有关,提示Skp2蛋白可能与前列腺癌的发生发展有关.     

PTEN抑癌基因在人胃癌组织中的表达及意义

目的探讨抑癌基因PTEN在胃癌组织中的表达水平及与其生物学行为的关系。方法应用免疫组织化学EnVision法检测116例胃癌组织,35例癌旁异型组织,56例癌旁正常黏膜组织中的PTEN蛋白表达情况。结果胃癌组织中PTEN阳性率为53.4 %(62/116),显著低于异型增生、癌旁正常黏膜组织中的阳性率71.4 %(25/35)、100 %(56/56)(P<0.001)。在各组织学类型中,高中分化腺癌PTEN蛋白阳性表达率最高(72.7 %,32/44),显著高于印戒细胞癌(29.2 %,7/24),P<0.001。PTEN蛋白的表达与淋巴结转移、侵袭程度密切相关(P<0.05)。结论PTEN基因的异常改变与胃癌的发生发展密切相关,可能是胃癌进一步恶化的标志之一,可作为胃癌生物学行为的参考指标,为胃癌的基因治疗提供参考依据。     

pAkt、Skp2和P27kip1蛋白在肝细胞癌中的表达及意义

目的探讨人肝细胞癌组织中pAkt、Skp2和P27kip1蛋白的表达及其临床意义。方法应用免疫组织化学方法检测78例肝细胞癌及21例正常肝组织中pAkt、Skp2和P27kip1蛋白的表达,分析其与肝细胞癌临床病理特征及预后的关系。结果肝细胞癌组织中pAkt及Skp2蛋白的高表达率分别为43.6%和47.4%,显著高于正常肝组织(P＜0.05),P27kip1蛋白的阳性表达率为34.6%,显著低于正常肝组织(P＜0.05)。pAkt蛋白的表达与肿瘤直径、侵犯周围脏器或淋巴结转移及TNM分期有关(P＜0.05);Skp2蛋白的表达与肿瘤直径、门静脉癌栓及TNM分期有关(P＜0.05);P27kip1蛋白的表达与肿瘤直径、数目及TNM分期有关(P＜0.05)。Skp2与pAkt蛋白表达呈正相关(r=0.356,P=0.001),与P27kip1蛋白表达呈负相关 (r=-0.313, P=0.005)。pAkt、Skp2蛋白高表达患者术后生存率明显低于低表达患者(P=0.000),P27kip1蛋白的表达与患者术后生存率无关。Cox模型多因素分析结果显示,TNM分期、pAkt及Skp2蛋白的表达是影响肝细胞癌预后的独立因素。结论肝细胞癌组织中pAkt、Skp2及P27kip1蛋白的表达失调与肝细胞癌的恶性生物学行为密切相关,pAkt及Skp2可以作为评价患者预后的指标。     

胃癌组织MACC1表达及其临床意义分析

目的:研究结肠癌转移相关基因1(MACC1)在胃癌组织中的表达及其临床意义。方法:采用RT-qPCR检测胃癌组织株和67例胃癌组织及癌旁正常组织中MACC1mRNA的表达,免疫组化技术检测67例胃癌组织及癌旁正常组织中MACC1蛋白的表达,并分析其与临床病理资料的关系。结果:BGC823、SGC7901和MGC803 3种胃癌细胞株中MACC1mRNA的相对表达量分别为3.458 4±0.047 9、4.768 5±0.100 6和4.257 5±0.029 5,差异有统计学意义,F=295.131,P<0.05。癌组织MACC1mRNA表达量(5.560 0±2.853 1)较癌旁正常组织(2.190 1±1.675 9)显著增高,t=6.907,P=0.000。肿瘤组织中MACC1蛋白的阳性率为64.18%(43/67),显著高于癌旁正常组织5.97%(4/67),χ2=49.844,P<0.05,且MACC1蛋白的异常高表达与分化程度(χ2=14.492,P=0.000)、腹膜转移(χ2=4.251,P=0.039)、淋巴转移(χ2=11.978,P=0.001)、临床分期(χ2=11.024,P=0.001)密切相关,而与年龄(χ2=0.129,P=0.720)、性别(χ2=0.407,P=0.523)、肿瘤大小(χ2=0.017,P=0.897)、部位(χ2=3.021,P=0.082)及远处转移(χ2=0.000,P=1.000)无关。结论:MACC1可以作为预测腹膜转移、淋巴转移,评价胃癌进展的有效指标,可为胃癌患者的临床诊疗提供依据。     

非小细胞肺癌Survivin和Skp2的表达及其临床意义

目的 检测Survivin和Skp2蛋白在非小细胞肺癌中的表达,探讨其相互关系及临床意义.方法 用实时定量PCR的方法检测30例非小细胞肺癌组织及其对应的癌旁组织中survivin mRNA的表达,应用免疫组织化学法检测50例非小细胞肺癌组织中Survivin和Skp2的表达,统计Survivin与病理特征及Skp2的关系.结果 76.7%(23/30)肿瘤组织survivin mRNA表达量明显高于对应的癌旁组织.Survivin蛋白在癌组织的阳性表达率(74.0%)显著高于癌旁组织(16.7%),χ2=25.9,P<0.001.Skp2在非小细胞肺癌组织中的阳性表达率(70.0%)也显著高于癌旁组织(20.0%),χ2=18.8,P<0.001).Survivin表达与非小细胞肺癌的病理类型、分化程度、肿瘤分期以及是否有淋巴结转移无统计学意义的相关性(P>0.05).Survivin表达与Skp2表达呈正相关(χ2=8.32,P<0.05).结论 Survivin在肺癌组织中高表达,其阳性表达率与肿瘤病理类型、肿瘤分期、细胞分化程度和淋巴结转移无明显相关性,与Skp2表达呈正相关.     

组织芯片检测p16蛋白在不同胃组织中的表达意义

[目的]分析胃癌相关差异表达蛋白p16在不同胃组织中的表达意义,为临床早期发现胃癌及评估胃癌患者预后提供有价值的资料.[方法]采用免疫组织化学染色,检测胃组织芯片(包括正常胃黏膜、癌旁、非典型增生、胃癌及淋巴结转移癌组织)中p16蛋白的表达,分析其在胃癌组织中表达与临床病理特征的关系.[结果] p16蛋白在正常胃黏膜、癌旁、非典型增生和胃癌组织中的表达率分别为76.47％ (26/34)、79.59％( 39/49)、34.62％ (9/26)和8.64％(7/81);p16蛋白在胃癌组织中阳性表达率较正常胃黏膜、癌旁组织和非典型增生组织降低(P＜0.01),而非典型增生组织中阳性表达率较正常胃黏膜和癌旁组织降低(P＜0.05);p16蛋白表达与胃癌患者年龄、肿块大小和淋巴结转移有关(P＜0.05).[结论] p16蛋白表达与胃癌的发生发展、患者年龄、肿块大小及淋巴结转移有关.     

胃癌组织Cystatin SN mRNA表达及其临床意义的探讨

目的:研究半胱氨酸蛋白酶抑制剂1 (Cystatin SN)在胃癌组织中的表达及临床意义.方法:荧光定量PCR方法检测40例胃癌组织和40例癌旁组织中Cystatin SN的表达.结果:胃癌组织中Cystatin SN mRNA的表达水平为5.370 0±3.034 5,相应的癌旁组织为1.705 0±0.738 8,癌组织显著高于癌旁组织,t=8.297,P=0.000.Cystatin SN的表达与肿瘤大小(t=-0.646,P=0.001)、淋巴转移(t=3.393,P=0.002)、TNM分期(t=-3.798,P=0.001)和浸润程度(t=4.904,P=0.000)相关,与肿瘤的分化程度、患者年龄和性别无关,P＞0.05.结论:Cystatin SN在胃癌组织中的高表达与胃癌的发生发展密切相关.     

Significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression

Objective： S-phase kinase-associated protein 2 （Skp2） is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods： Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results： Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa （P=0.000, all the same）. Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma （P=0.037）. Skp2 labeling frequency % was positively associated with differentiated degree （rho=0.315, P=0.000）, vessel invasion （rho=0.303, P=0.000） and lymph node metastasis （rho=0.254, P=0.000） respectively. An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma （rho=-0.451, P=0.000） and with its putative negative regulator, the PTEN tumor suppressor protein （rho=-0.480, P=0.000）. p27 expression had positive relationship with PTEN expression in gastric carcinoma （rho=0.642, P=0.000）. Conclusion： Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma： elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression. These suggest that PTEN may regulate expression of p27 through the Skp2 pathway, and the effects of Skp2, p27 and PTEN together play an important role in carcinogenesis and progression of gastric carcinoma.     

PTEN、p27蛋白在胃癌组织中的表达及其相关性

 目的　研究胃癌组织中PTEN和p27蛋白的表达及二者间的相关性。方法　应用免疫组织化学方法检测49例胃癌组织、49例癌旁组织和13例正常胃黏膜中PTEN和p27蛋白的表达情况。结果　胃癌组织中PTEN和p27蛋白的阳性表达率分别为61.22 %（30／49）和57.14 %（28／49）,较癌旁组[91.84 %（45／49）、93.88 %（46／49）]和正常组织[100 %（13／13）、100 %（13／13）]明显降低（均P＜0.05）。两者在胃癌中的表达有相关性（r＝0.580,P＝0.000）,且均与肿瘤的分化程度、淋巴结转移和PTNM分期有关。结论　PTEN和p27基因的异常改变可能参与胃黏膜细胞的恶性转化过程,且两者之间存在相关性。联合检测两者表达水平可作为评价胃癌病理生物学行为的客观指标之一。     

Survivin在早期胃癌及癌前病变中的表达及其与PTEN表达的关系

目的：探讨Survivin在早期胃癌及癌前病变中的表达及其与PTEN表达的关系。方法：采用免疫组化SP法检测Survivin、PTEN基因蛋白在30例正常胃黏膜、20例不完全型大肠化生,93例轻、中、重度不典型增生和54例早期胃癌中的表达。结果：Survivin在正常胃黏膜不表达（0/30）,在不完全型大肠化生的阳性表达率为5.00%（1/20）;在轻、中和重度不典型增生的阳性率分别为6.25%（2/32）、8.57%（3/35）和65.73%（17/26）,其中轻、中度不典型增生与重度不典型增生的差异有统计学意义,P〈0.05。在早期胃癌中阳性表达率为68.51%（37/54）。Survivin基因在早期胃癌中的阳性与阴性表达中PTEN的阳性表达呈明显负相关,r=-0.564,P=0.0000。结论：Survivin在早期胃癌中表达上调,说明该基因在早期胃癌的发生过程中作用重要,Survivin表达越高,早期胃癌的分化程度越低。早期胃癌中Survivin的阳性表达与PTEN阳性表达密切相关。     

Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis.

PURPOSE: The F-box protein S-phase kinase-associated protein 2 (Skp2) positively regulates the G(1)-S phase transition by controlling the stability of several G(1) regulators, such as p27Kip1. However, the clinical significance of Skp2 in patients with acute myelogenous leukemia (AML) remains unknown. EXPERIMENTAL DESIGN: We examined the clinical and biological significance of Skp2 expression in AML and evaluated the relationship between Skp2 and p27Kip1 expression and phosphatase and tensin homologue (PTEN) phosphorylation. RESULTS: Western blot analysis showed that high Skp2 expression was observed in 57 (57.6%) cases and significantly correlated with unfavorable cytogenetics (P = 0.035) but not with age, white blood cell count, serum lactic dehydrogenase level, and the French-American-British subtype. An inverse correlation was not observed between Skp2 and p27Kip1 expression. However, p27Kip1 protein was preferentially localized to cytoplasm in the high-Skp2-expression group. The cytoplasmic to nuclear ratio of p27Kip1 expression was significantly correlated with the levels of Skp2 expression (P < 0.001). The frequency of PTEN phosphorylation was significantly higher in the high-Skp2-expression group compared with the low- Skp2-expression group (P = 0.035). The Skp2 overexpression was significantly associated with shorter disease-free survival and overall survival (P = 0.0386 and P = 0.0369, respectively). Multivariate analysis showed that Skp2 expression was an independent prognostic factor both in the disease-free survival and overall survival. CONCLUSION: These findings suggest that Skp2 expression is an independent marker for a poor prognosis in AML. The presence of a positive correlation between Skp2 and phosphorylated PTEN suggests that an aberration in the PTEN/Skp2 signaling pathway might be operating in AML.     

P16INK4A和PTEN在高危型HPV相关宫颈癌组织中的表达及意义

背景与目的:高危型人乳头状瘤病毒(high-risk human papillomavirus,HR-HPV)是宫颈癌最主要的致病因素,目前研究发现,在宫颈上皮癌变过程中,P16INK4A的异常表达和HR-HPV感染密切相关;同时,另一抑癌基因PTEN也参与了宫颈上皮肿瘤的形成.本研究旨在探讨宫颈上皮癌变过程中P16INK4A、PTEN表达与HR-HPV感染的关系及其意义.方法:应用免疫组织化学方法检测P16INK4A蛋白和PTEN蛋白在30例正常宫颈组织、11例原位癌、24例宫颈浸润癌组织中的表达.用第二代杂交捕获法(HC-2)检测每一病例的13种HR-HPV DNA.结果:HR-HPV和P16INK4A阳性率浸润癌组(91.7%、87.5%)和原位癌组(90.9%、81.8%)都明显高于正常宫颈组(30.0%、6.7%),差异有统计学意义(P＜0.001).P16INK4A过表达(中、强阳性)和HR-HPV阳性同时出现有30例,其中原位癌组9例,浸润癌组21例;两者同时阴性有23例,其中正常宫颈组20例,原位癌组1例,浸润癌组2例.相关性分析结果显示,HR-HPV感染与P16INK4A表达呈正相关(rs=0.690,P＜0.001).26例PTEN中、强阳性表达均在正常宫颈组,其阳性率在浸润癌组(37.5%)和原位癌组(36.4%)明显低于正常宫颈组(83.3%),差异有统计学意义(P＜0.01).相关性分析证实,HR-HPV感染与PTEN表达的相关性无统计学意义(rs=-0.174,P=0.167).结论:在HR-HPV感染的宫颈癌中,P16INK4A出现过表达,其蛋白的肿瘤抑制功能不明显;PTEN独立于HR-HPV途径,以其功能下调促进宫颈癌的发生、发展.     

Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression,possibly via p27 proteolysis

Reduced expression level of p27, a cyclin-dependent kinase inhibitor, is associated with high aggressiveness and poor prognosis of various malignant tumors, including gastric carcinoma. S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of substrate-recognition subunits of Skp1-Cullin-F-box ubiquitin-protein ligase complexes, is necessary for p27 ubiquitination and degradation. In the present study, we examined the clinical and biological significance of Skp2 expression in human gastric carcinoma and the relationship between the expression of Skp2 and p27. Northern blot analysis showed that Skp2 mRNA was overexpressed in carcinoma tissues (P < 0.05), and the high Skp2 expression group showed significantly poorer prognosis in 98 patients with gastric carcinoma (P < 0.05). Immunohistochemical analysis showed that Skp2 protein was expressed predominantly in carcinoma cells. We also found an inverse correlation between the expression of Skp2 mRNA and p27 protein in vivo (P < 0.01). To analyze the biological behavior of Skp2, we established stably Skp2-transfected gastric carcinoma cell lines. Western blot analysis showed that Skp2-transfected cells expressed lower levels of p27 protein than the control cells. Skp2-transfected cells showed significantly higher levels of growth rate (P < 0.05), percentage of bromodeoxyuridine-positive cells after serum starvation (P < 0.01), resistance to apoptosis induction by actinomycin D treatment (P < 0.05), and invasion potential (P < 0.01) than the control cells. These findings indicate that Skp2 expression can modulate the malignant phenotype of gastric carcinoma, possibly via p27 proteolysis. Skp2 can play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinoma as well as a strong prognostic marker.     

Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas

Hypoxia-inducible factor-1 (HIF-1)alpha expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20), Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The relationship between HIF-1alpha expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1alpha expression was not observed in normal gastric mucosa but increased in density (P<0.01) and intensity (P<0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for cancer-specific survival (P=0.019). In univariate analysis and in comparison with tumours not expressing HIF-1alpha, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0-2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5-1.2). Hypoxia-inducible factor-1alpha lost prognostic significance in multivariate analysis. The results suggest HIF-1alpha is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.     

抑癌基因PTEN、一氧化氮合酶与胃癌的关系及临床意义

目的检测抑癌基因PTEN编码蛋白、iNOS在正常胃粘膜及胃癌组织中的表达情况,探讨PTEN、iNOS与胃癌发生发展的关系及作用机理.方法采用免疫组织化学S-P法进行检测.结果 10例正常胃粘膜均可见PTEN蛋白的强表达,40例胃癌组织中28例PTEN蛋白表达较正常胃粘膜明显下降或缺失,差异有显著性(P＜0.01),与胃癌的分化程度、浸润深度、TNM分期、淋巴结转移显著相关(P＜0.05).iNOS在胃癌组织中的表达显著高于正常胃粘膜组,(72.5%vs10%,P＜0.01),与胃癌的浸润深度、淋巴结转移、TNM分期显著相关(P＜0.05).在PTEN蛋白阴性的胃癌组中,iNOS阳性率为93.8%,显著高于PTEN阳性组(P＜0.05).结论抑癌基因PTEN编码蛋白在胃癌及胃癌发展过程中表达逐渐下降或缺失,与iNOS之间可能存在相互作用,协同参与了胃癌的发展、转移及浸润.PTEN蛋白表达可作为判定胃癌生物学行为的临床参考指标.