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Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions

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World Journal of Gastroenterology 2009年第32期15卷 4055-4061页

作者： Chun-Li Da Yan Xin Jing Zhao Xiang-Dong Luo The Fourth Laboratory of Cancer Institute Department of Tumor Pathology of General Surgery Institute the First Hospital of China Medical University Shenyang 11000 1 Liaoning Province China

AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous ***: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric ***: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<***: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.

关键词： Apoptosis Cell proliferation Gastric cancer Immunohistochemistry Neoplastic processes Survivinprotein Yes-associated protein

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Quantitative analysis of tumor mitochondrial RNA using microarray

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World Journal of Gastroenterology 2005年第1期11卷 36-40页

作者： Cheng-BoHan Xiao-YunMao YanXin Shao-ChengWang Jia-MingMa Yu-JieZhao CancerInstitute FirstAffiliatedHospitalChinaMedicalUniversityShenyang1lO001LiaoningProvinceChina BiochlpCenter ChinaMedicalUniversityShenyang110001LiaoningProvinceChina

AIM: To design a novel method to rapidly detect the quantitative alteration of mtRNA in patients with ***: Oligo 6.22 and Primer Premier 5.0 bio-soft were used to design 15 pairs of primers of mtRNA cDNA probes in light of the functional and structural property of mtDNA, and then RT-PCR amplification was used to produce 15 probes of mtRNA from one normal gastric mucosal tissue. Total RNA extracted from 9 gastric cancers and corresponding normal gastric mucosal tissues was reverse transcribed into cDNA labeled with fluorescein. The spotted mtDNA microarrays were made and hybridized. Finally,the microarrays were scanned with a GeneTACTM laser scanner to get the hybridized results. Northern blot was used to confirm the microarray ***: The hybridized spots were distinct with clear and consistent backgrounds. After data was standardized according to the housekeeping genes, the results showed that the expression levels of some mitochondrial genes in gastric carcinoma were different from those in the corresponding non-cancerous ***: The mtDNA expression microarray can rapidly, massively and exactly detect the quantity of mtRNA in tissues and cells. In addition, the whole expressive information of mtRNA from a tumor patient on just one slide can be obtained using this method, providing an effective method to investigate the relationship between mtDNA expression and tumorigenesis.

关键词： Mitochondrial RNA Gastric cancer Microarray technique

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Mutations of mitochondrial 12S rRNA in gastric carcinoma and their significance

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World Journal of Gastroenterology 2005年第1期11卷 31-35页

作者： Cheng-BoHan Jia-MingMa YanXin Xiao-YunMao Yu-JieZhao Dong-Yingwu Su-MinZhang Yu-KuiZhang CancerInstitute theFirstAffiliatedHospitalChinaMedicalUniversityShenyang110001LiaoningProvinceChina BiochipsCenter ChinaMedicalUniversityShenyang110001LiaoningProvinceChina

AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric ***: PCR amplified mitochondrial 12S rRNA of 44 samples including 22 from gastric carcinoma tissues and 22 from adjacent normal tissues, was detected by direct DNA sequencing. Then laser capture microdissection technique (LCM) was used to separate the cancerous cells and dysplasia cells with specific mutations. Denaturing high performance liquid chromatography (DHPLC) plus allele-specific PCR (ASPCR), nest-PCR and polyacrylamide gel electrophoresis (PAGE)were used to further evaluate this mutant property and quantitative difference of mutant type between cancerous and dysplasia cells. Finally, RNAdraw biosoft was used to analyze the RNA secondary structure of mutant-type 12S ***: Compared with Mitomap database, some new variations were found, among which np652 G insertion and np716 T-G transversion were found only in cancerous *** was a statistic difference in the frequency of 12S rRNA variation between intestinal type (12/17, 70.59%) and diffusive type (5/17, 29.41%) of gastric carcinoma (P＜0.05).DHPLC analysis showed that 12S rRNA np652 G insertion and np716 T-G transversion were heteroplasmic *** frequency of 12S rRNA variation in cancerous cells was higher than that in dysplasia cells (P＜0.01). 12S rRNA np652 G insertion showed obviously negative effects on the stability of 12S rRNA secondary structure, while others such as T-G transversion did ***: The mutations of mitochondrial 12S rRNA may be associated with the occurrence of intestinal-type gastric carcinoma. Most variations exist both in gastric carcinomas and in normal tissues, and they might not be the characteristics of tumors. However, np652 G insertion and np716 T-G transversion may possess some molecular significance in gastric carcinogenesis. During the

关键词： Gastric carcinomas Mitochondrial 12S rRNA Variation

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Loss of heterozygosity and microsatellite instabilities of fragile histidine triad gene in gastric carcinoma

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World Journal of Gastroenterology 2006年第23期12卷 3766-3769页

作者： Yu-Ping Xiao Dong-Ying Wu Lei Xu Yan Xin Cancer Insititute No.1 Hospital of China Medical University Shenyang 110001Liaoning Province China Fourth Laboratory of Cancer Institute No.1 HospitalChina Medical University Shenyang 110001 Liaoning ProvinceChina

AIM： To detect the loss of heterozygosity （LOH） and microsatellite instabilities （MSI） of fragile histidine triad （FHIT） gene in gastric carcinoma and to study their association with the clinical pathological characteristics of gastric carcinoma. METHODS： LOH and MSI of FHIT gene were detected at four microsaterllite loci D3SI3H, D3S4103, D3SI481 and D3S1234 using PCR in matched normal and cancerous tissues from 50 patients with primary gastric cancer. RESULTS： The average frequency of LOH and MSI of FHIT gene in gastric cancer was 32.4% and 26.4% respectively. LOH and MSI of FHIT gene in gastric cancer had no association with histological, Borrmann, and Lauren＇s classification. LOH of FHIT gene in gastric cancer was related to invasive depth. The frequency of FHIT LOH in gastric cancer with serosa-penetration was obviously higher than that in gastric cancer without serosa-penetration （73.5% vs 37.5%, P 〈 0.05）. MSI of FHIT gene in gastric cancer was associated with the lymph node metastasis. The frequency of MSI in gastric cancer without lymph node metastasis was significantly higher than that in gastric cancer with lymph node metastasis （66.7% vs 34.3%, P 〈 0.05）. CONCLUSION： LOH of FHIT gene is correlated with invasive depth of gastric carcinoma. MSI of FHIT gene is correlated with lymph node metastases. LOH and MSI of FHIT gene play an important role in carcinogenesis of gastric cancer.

关键词： Gastric cancer FHIT gene Microsatellite instabilities

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Pathobiological behavior and molecular mechanism of signet ring cell carcinoma and mucinous adenocarcinoma of the stomach:A comparative study

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World Journal of Gastroenterology 2004年第5期10卷 750-754页

作者： Xue-FeiYang LinYang Xiao-YunMao Dong-YingWu Su-MinZhang YanXin TheFourthLaboratory CancerInstituteTheFirstAffiliatedHospitalofChinaMedicalUniversityShenyang110001LiaoningProvinceChina DepartmentofPathology CancerHospitalChineseAcademyofMedicalSciencesBeijing100021China

AIM:To elucidate the distinctive pathobiological behavior between signet ring cell carcinoma (SRC) and mucinous adenocarcinoma of the ***: Based on the histological growth patterns and cell-functional differentiation classifications of stomach carcinoma, we conducted a series of comparative *** paraffin-embedded and frozen blocks were collected from the files of Cancer Institute of China Medical University. On the basis of histopathological observation, we applied enzymatic and mucous histochemistry, immunohistochemistry,flow cytometry (FCM) and molecular biology to compare these two categories of gastric cancers in terms of the DNA ploidy, proliferative kinetics, the expression of gastric carcinoma associated gene product and instabilities of mitochondrial DNA (mtDNA).RESULTS:Gastric SRC was commonly seen in females below 45 years, mostly presenting diffuse growth and ovary or uterine cervix metastasis. The majority of SRC were absorptive and mucus-producing functional differentiation type (AMPFDT), which growth relied on estrogen. Meanwhile,stomach mucinous adenocarcinomas were mostly observed in males over 50 years, prone to massive growth or nest growth and extensive peritoneal infiltration, showing two categories of cell-functional differentiation types: AMPFDT and mucus-secreting functional differentiation type (MSFDT).Expressions of ER, enzyme c-PDE and 67kDaLN-R in SRC were evidently higher than that in mucinous adenocarcinoma,while expressions of LN, CN-Ⅳ, CD44v6, and PTEN protein were obviously lower in SRC than that in mucinous adenocarcinoma (P0.05) between the above two gastric ***: Though SRC and mucinous adenocarcinoma were both characterized by abundant mucus-secretion, they were quite different in morphology, ultrastructure, cell-functional differentiation and protein expression, indicating different mechanisms of carcinogenesi

关键词：环状体细胞癌粘蛋白状腺癌胃癌病理形态学分子机制细胞增殖

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MSI/LOH and extron expression of the FHIT gene in gastric carcinoma

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Frontiers of Medicine 2007年第1期1卷 99-103页

作者： XIAO Yuping MAO Lili HAN Chengbo LI Jinyi XU Lei XIN Yan Cancer Institute the First Affiliated HospitalChina Medical UniversityShenyang 110001China

We detected loss of heterozygosity(LOH)and microsatellite instabilities(MSI),as well as extron expression of the fragile histidine triad(FHIT)gene in gastric carcinoma(GC),in order to evaluate their association with clinicopathological processes in gastric *** and MSI of the FHIT were detected by using PCR at 4 microsatellite loci:D3S 1300,D3S 4103,D3S 1481,D3S 1234 in cancer tissues from 50 patients with primary GC,with normal mucosa acting as matched *** transcripts were detected by nested RT-PCR in 30 cases of GC and their products were *** show that the average frequencies of LOH and MSI of the FHIT gene in GC were 32.4%and 26.4%,*** was no correlation between LOH and MSI of the FHIT gene in GC and the histological characteristics of gastric carcinoma(Bormann’s or Lauren’s classification).LOH of the FHIT gene in GC was related to depth invasiveness,and its frequency in GC where serosa was penetrated was significantly higher than that in GC without serosa penetration(73.5%vs 37.5%,P<0.05).The frequency of MSI in GC without lymph node metastasis was significantly higher than that in GC with lymph node metastasis(66.7%vs 34.3%,P<0.05).Aberrant transcripts were found in 11/30 GC *** analysis of the aberrant fragments found a RT-PCR product missing exons 5–7 in one case of GC,and another product missing exons 4–*** of 10(40.0%)cases of primary GC showed absent or decreased expression of the FHIT protein as compared to their matched normal *** findings in this study suggest that LOH and MSI of FHIT gene may induce aberrant extron expression,which might play a role in gastric carcinogenesis.

关键词： gene expression regulation neoplastic microsatellite instabilities loss of heterozygosity fragile histidine triad protein stomach

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利用组织芯片技术研究COX-2在胃癌中的表达及其与血管生成的关系

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世界华人消化杂志 2006年第6期14卷 550-556页

作者：吕晓君毛晓韵李锦毅韩琤波吴东瑛张淑敏辛彦中国医科大学附属第一医院肿瘤研究所第四研究室辽宁省沈阳市110001 武警总医院中心实验室北京市海淀区100039

目的:研究COX-2在胃癌中的表达及其与血管生成的关系,探讨其在胃癌转移中的作用及与胃癌病理生物学行为的关系．方法:采EnVision方法检测胃癌组织芯片中 COX-2的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性．... 详细信息

目的:研究COX-2在胃癌中的表达及其与血管生成的关系,探讨其在胃癌转移中的作用及与胃癌病理生物学行为的关系．方法:采EnVision方法检测胃癌组织芯片中 COX-2的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性．结果:COX-2在胃癌中的表达明显高于正常胃黏膜(P=0．001)．COX-2的高表达与胃癌的转移(P=0．019)和胃壁浸润深度(0．031)呈正相关,与胃癌的组织病理分型无关(P=0．495), 与Borrmann分型无关(P=0．109)组织MVD (65．49±20．64)明显高于正常胃黏膜组织 (36．21±18．47,P=0．001)．MVD值与胃癌的组织病理分型(P=0．003)和转移有关(P=0．043), 与胃癌胃壁浸润深度(P=0．627)和Borrmann 分型(P=0．634)无明显相关性．COX-2表达阳性组的MVD指数明显高于COX-2表达阴性组 (68．59±19．8 vs 25．82±7．76．P<0．05),COX-2 表达与MVD呈正相关(P=0．001)．结论:组织芯片技术对于快速检测胃癌及其他肿瘤的分子病理学改变是一个强有力的工具．COX-2表达可能通过促进血管形成对胃癌的发生、发展起重要作用,其可作为判断预后和指导治疗的有效指标．

关键词：胃癌环氯合酶组织芯片微血管密度血管生成胃黏膜

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胃癌前病变及胃癌组织中survivin和caspase-3蛋白表达的意义

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世界华人消化杂志 2005年第16期13卷 1951-1955页

作者：吕晓君吴东瑛杨琳张淑敏辛彦中国医科大学附属第一医院肿瘤研究所第四研究室辽宁省沈阳市110001 中国医学科学院中国协和医科大学肿瘤医院病理科北京市100021

目的:检测survivin和caspase-3蛋白在胃癌前病变及胃癌组织中的表达情况,探讨其与胃黏膜癌变的关系及作用机制.方法:采用Envision免疫组化学二步法检测不同胃黏膜病变组织131例(包括慢性炎症44例、单纯肠化生31例,异型增生40例和胃癌16... 详细信息

目的:检测survivin和caspase-3蛋白在胃癌前病变及胃癌组织中的表达情况,探讨其与胃黏膜癌变的关系及作用机制.方法:采用Envision免疫组化学二步法检测不同胃黏膜病变组织131例(包括慢性炎症44例、单纯肠化生31例,异型增生40例和胃癌16例)中survivin和caspase-3蛋白的表达情况.结果:慢性炎症,单纯肠化生,异型增生和胃癌中的survivin蛋白阳性表达率分别为4.5%(2/44),51.6%(15/31),100.0%(40/40)和93.8%(15/16).胃癌组织和异型增生组survivin蛋白表达显著高于单纯肠化生组(P<0.05).胃癌survivin蛋白表达阳性组caspase-3蛋白表达(3/13,23.1%)显著低于survivin蛋白表达阴性组(2/3,66.7%,P<0.05).结论:胃癌survivin蛋白表达水平与异型增生相当,高于单纯肠化生,survivin可能通过阻抑caspase-3促进胃癌的演进.

关键词：胃癌 Survivin Caspase-3 癌前病变 caspase-3蛋白 survivin蛋白蛋白表达水平胃癌组织胃癌前病变 Envision

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胃癌组织KAI 1和nm23-H_1蛋白的表达意义

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世界华人消化杂志 2005年第23期13卷 2726-2730页

作者：孟丽辉辛彦吴东瑛张淑敏中国医科大学附属第一医院肿瘤研究所第四研究室辽宁省沈阳市110001

目的:观察胃癌组织中KAI 1和nm23-H1蛋白的表达与临床病理生物学的关系,探讨KAI 1蛋白在胃癌发生、发展中的作用．方法:应用兔抗人KAI 1多克隆抗体和鼠抗人nm23-H1 单克隆抗体对87例手术切除胃癌标本以PV-9000免疫组化二步法进行染色,... 详细信息

目的:观察胃癌组织中KAI 1和nm23-H1蛋白的表达与临床病理生物学的关系,探讨KAI 1蛋白在胃癌发生、发展中的作用．方法:应用兔抗人KAI 1多克隆抗体和鼠抗人nm23-H1 单克隆抗体对87例手术切除胃癌标本以PV-9000免疫组化二步法进行染色,用x2检验进行统计学分析．结果:伴有淋巴结转移的胃癌组织中KAI 1蛋白表达阳性率(60％,39／65)明显低于无淋巴结转移的胃癌组织(95％,21／22,P<0．05),早中期胃癌组织中KAI 1蛋白表达阳性率(94％,16／17)显著高于晚期胃癌组织(63％, 44／70,P<0．05),KAI 1蛋白高表达者其生存期亦较长 (P<0．05);伴有淋巴结转移的胃癌组织中nm23-H1蛋白表达阳性率明显低于无淋巴结转移的胃癌组织(18％ vs 77％,P<0．05),早中期胃癌组织nm23-H1蛋白表达阳性率明显高于晚期胃癌组织(65％vs26％,P<0．05)．结论:KAI 1和nm23-H1蛋白均与胃癌侵袭转移有关, 且KAI 1表达与胃癌患者预后密切相关,将两种指标联合检测,可作为正确判断胃癌患者预后,指导临床治疗的分子生物学指标．

关键词： KAI 1 nm23-H1 胃癌预后

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FHIT及nm23-H_1基因编码蛋白表达与胃癌临床病理生物学行为

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世界华人消化杂志 2004年第11期12卷 2534-2538页

作者：高余佳毛晓韵吴东瑛张淑敏辛彦中国医科大学附属一院肿瘤研究所第四研究室辽宁省沈阳市110001

目的:观察脆性组氨酸三联体(FHIT)基因和nm23基因在胃癌中的表达,探讨其与胃癌临床病理因素的关系. 方法:采用PV9000免疫组化二步法检测98例胃癌组织中FHIT和nm23蛋白的表达. 结果:FHIT和nm23在胃癌中表达率分别为38.8%(38/98)和33%(28/... 详细信息

目的:观察脆性组氨酸三联体(FHIT)基因和nm23基因在胃癌中的表达,探讨其与胃癌临床病理因素的关系. 方法:采用PV9000免疫组化二步法检测98例胃癌组织中FHIT和nm23蛋白的表达. 结果:FHIT和nm23在胃癌中表达率分别为38.8%(38/98)和33%(28/87).FHIT蛋白的缺失在胃癌中占62.1%.胃癌中FHIT的缺失与组织学类型,Lauren分型和淋巴结转移相关(P0.05).nm23蛋白阳性表达与临床病理分期,淋巴结转移呈负相关(P<0.05). 结论:胃癌组织中FHIT蛋白的缺失是频发事件,FHIT可能是胃癌发生中重要的侯选抑癌基因.FHIT及nm23基因编码蛋白在胃癌中的表达与胃癌淋巴结转移密切相关,且可能共同起作用,可作为临床预测转移及估计预后的重要指标.

关键词： FHIT nm23-H1 基因编码蛋白表达胃癌病理生物学

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