两种方法检测胃癌患者CHFR基因启动子区甲基化的状态

背景与目的:目前认为CpG岛甲基化导致转录抑制是恶性肿瘤发生的重要机制之一.微管抑制剂诱发有丝分裂应激时,CHFR基因能够控制细胞分裂的进行.本研究检测胃癌中CHFR基因启动子区甲基化状态,探讨该基因甲基化状态与胃癌临床病理特征的关系;并比较甲基化特异性PCR方法(methylationsoecific polymerase chain reaction, MSP)和结合重亚硫酸盐的限制性内切酶法(combined bisulfite restriction analysis, COBRA)在检测胃癌组织CHFR基因甲基化状态的差异性.方法:首先采用MSP方法检测64例胃癌患者胃癌组织和相对应的癌旁正常组织中CHFR基因肩动子区的甲基化状态,然后采用COBRA方法检测64例胃癌患者胃癌组织中CHFR基因启动子区的甲基化状态,并将检测结果结合各病例的临床特征进行分析.结果:MSP方法检测结果显示,51.6%的胃癌组织和18.8%的癌旁正常组织中存在CHFR基因异常甲基化,两者之间的差异有统计学意义(P<0.001);CHFR基因启动子区异常甲基化状态在不同临床病理学特征(包括年龄、性别、肿瘤大小、病理分期、Borrman分型、肿瘤浸润深度、组织分化程度和淋巴转移程度)的胃癌组织和癌旁组织中的差异无统计学意义(P值均>0.05).COBRA方法检测结果显示.肿瘤组织CHFR甲基化阳性率为42.2%(27/64.),与MSP方法检测结果的差异无统计学意义(P>0.05).结论:CHFR基因异常甲基化是胃癌发生过程中的频发事件,检测胃黏膜组织中CHFR基因异常甲基化状态可能有助于胃癌的诊断.对于胃癌组织CHFR基因启动子区甲基化的检测,MSP与COBRA两种方法没有明显差异.     

CDH11甲基化在宫颈癌中的表达及临床意义

目的:探讨钙黏附蛋白11（cadherin-11,CDH11)甲基化在宫颈癌中的表达及临床意义。方法:应用甲基化特异性聚合酶链反应检测 CDH11 基因在 3株宫颈癌细胞系、1 株人表皮永生化细胞株、30 例宫颈癌组织、17 例正常宫颈组织中的甲基化状态。统计患者临床资料,分析甲基化同临床病理特征之间的联系。结果:CDH11 在3 株宫颈癌细胞系中,均出现不同程度甲基化;在1 株人表皮永生化细胞株中未检测到甲基化。CDH11 在宫颈癌组织中的甲基化率为 56.7%（17/30）,显著高于正常宫颈组织23.5%（4/17）,差异具有统计学意义（P＜0.05）。CDH11 基因甲基化在不同分期的宫颈癌组织中检出率无统计学意义（P＞0.05）;在不同年龄段、是否有淋巴结转移以及分化级别上,CDH11 基因的甲基化率差异无统计学意义（P＞0.05）。结论:宫颈癌组织中CDH11 基因甲基化水平高于正常宫颈组织,差异有统计学意义。CDH11 基因甲基化可能是宫颈癌独特的基因甲基化谱成员之一,可以成为宫颈癌早期诊断的新的标志物。     

Clinical significance of stanniocalcin expression in tissue and serum of gastric cancer patients

Purpose： Stanniocalcin（STC） has been recognized as a potential biomarker in a variety of cancers. The aim of this study was to examine STC1 and STC2 expression in tumor and serum samples from gastric cancer（GC） patients.
Methods： A total of 83 GC patients treated with radical resection were enrolled in this study. Immunohistochemistry was used to detect STC protein expression in paired tumor and adjacent normal tissues. Serum STC levels were determined by enzyme-linked immunosorbent assay（ELISA）. The receiver operating characteristics（ROC） curve was constructed to describe diagnostic specificity and sensitivity.
Results： Both of STC1 and STC2 protein expression were upregulated in GC tissues compared with that in normal ones. Moreover, the high/moderate of STC1 protein was significantly associated with lymph metastasis, clinical stage and adverse 3-year progression-free survival（PFS）. In addition, serum STC1 and STC2 expression in GC patients were much higher than that in patients with benign gastric disease, which decreased at postoperative 7-10 days. The sensitivity of serum STC protein also showed superiority over CEA and CA19-9.
Conclusions： STC upregulation plays an important role in GC development, and serum STC1 and STC2 might function as promising tumor markers for GC diagnosis and prognosis.     

Methylation profiling of normal individuals reveals mosaic promoter methylation of cancer-associated genes

Epigenetic silencing by promoter methylation of genes associated with cancer initiation and progression is a hallmark of tumour cells. As a consequence, testing for DNA methylation biomarkers in plasma or other body fluids shows great promise for detection of malignancies at early stages and/or for monitoring response to treatment. However, DNA from normal leukocytes may contribute to the DNA in plasma and will affect biomarker specificity if there is any methylation in the leukocytes. DNA from 48 samples of normal peripheral blood mononuclear cells was evaluated for the presence of methylation of a panel of DNA methylation biomarkers that have been implicated in cancer. SMART-MSP, a methylation specific PCR (MSP) methodology based on real time PCR amplification, high-resolution melting and strategic primer design, enabled quantitative detection of low levels of methylated DNA. Methylation was observed in all tested mononuclear cell DNA samples for the CDH1 and HIC1 promoters and in majority of DNA samples for the TWIST1 and DAPK1 promoters. APC and RARB promoter methylation, at a lower average level, was also detected in a substantial proportion of DNA samples. We found no BRCA1, CDKN2A, GSTP1 and RASSF1A promoter methylation in this sample set. Several individuals had higher levels of methylation at several loci suggestive of a methylator phenotype. In conclusion, methylation of many potential DNA methylation biomarkers can be detected in normal peripheral blood mononuclear cells, and is likely to affect their specificity for detecting low level disease. However, we found no evidence of promoter methylation for other genes indicating that panels of analytically sensitive and specific methylation biomarkers in body fluids can be obtained.     

Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and cancer tissues

Promoter hypermethylation of the ADAM23 gene, which is normally involved in cell‐to‐cell and cell‐to matrix adhesion, has been reported in pancreatic, breast and brain cancer, and recently the role of this gene was examined in gastric cancer. In this study, we analyzed ADAM23 expression in colorectal cancer cell lines and examined its methylation by methylation‐specific PCR (MSP) and bisulfate‐modified DNA sequencing analysis. Methylated cells were treated with 5‐aza‐2′‐deoxycytidine to restore the ADAM23 expression. We then examined ADAM23 methylation status in colorectal cancer tissues and their corresponding normal tissues. We found that ADAM23 was aberrantly silenced or expressed at very low levels in 28 of the 32 (88%) colorectal cancer cell lines. MSP analysis showed that ADAM23 was methylated in 29 of 32 (91%) colorectal cancer cell lines and attenuated expression of ADAM23 was found to be related to hypermethylation in its promoter region. Moreover, the CpG dinucleotide methylation threshold of 70–90% was found to be required for complete silencing. In addition, when some cell lines without ADAM23 expression were treated with 5‐aza‐2′‐deoxycytidine, ADAM23 was reexpressed. In colorectal cancer tissues, the promoter region of ADAM23 was hypermethylated in 36 of 76 (47%). These results demonstrated that ADAM23 may be down‐regulated by aberrant promoter hypermethylation during the progression of colorectal cancer. © 2008 Wiley‐Liss, Inc.     

IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells

Invasion and metastases of cancer cells are the main causes of treatment failure in cancer. IQ motif-containing GTPase activating protein 1 (IQGAP1), plays pivotal roles in intercellular adhesion, migration, invasion and metastases in various cancer cells. However, the role of another family member, IQGAP2, in carcinogenesis remains unknown. Here, we investigated IQGAP2 functions in gastric cancers. We found that IQGAP2 protein expression was lost in 5 of the 9 gastric cancer cell lines. Through analysis by the methylation-specific PCR, aberrant IQGAP2 methylation was detected in 3 gastric cancer cell lines. IQGAP2 mRNA was found to be activated after 5-aza-2'-deoxycytidine treatment of the methylation-positive cells. Moreover, IQGAP2 methylation was detected in 28 of the 59 (47%) primary gastric cancer tissues, but not in 12 normal gastric mucosa samples. Immunohistochemical staining revealed that 7 of the 8 (88%) gastric cancer tissues without methylation signals displayed IQGAP2 expression, whereas among 10 with methylation signals none expressed IQGAP2 (p = 0.0002), indicating that IQGAP2 methylation is highly associated with loss of the IQGAP2 expression in the primary gastric cancer tissues as well as gastric cancer cell lines. Furthermore, IQGAP2 methylation was also associated with tumor invasion and a poor prognosis. IQGAP2 knockdown with small interfering RNA increased the invasive capacity of a gastric cancer cell line. These results suggest that silencing of IQGAP2 by promoter methylation may contribute to gastric cancer development.     

乳腺癌中BRCA1、GSTP1和MGMT基因甲基化检测的临床意义

背景与目的：DNA甲基化是1种调节基因表达的重要机制,在肿瘤发生、发展中起重要作用。研究表明,在肿瘤诊断、预后及疗效判断方面,DNA甲基化是1种有潜在应用价值的肿瘤标志物。本研究通过对乳腺癌中组织标本中BRCA1,GSTP1和MGMT这3种与DNA修复功能有关基因的甲基化状态进行检测,探讨其临床应用价值。方法：在106例配对的乳腺癌及癌旁组织中,运用甲基化特异性PCR法,对BRCA1、GSTP1和MGMT基因的甲基化状况进行检测,统计分析它们与乳腺癌主要临床病理特征之间的关系。结果：在乳腺癌组织标本中,BRCA1、GSTP1和MGMT的甲基化频率分别为24.5%(26/106)、29.2%(31/106)和18.9%(20/106),明显高于对应癌旁组织7.5%(8/106)、11.3%(12/106)和4.7%(5/106)的甲基化频率,差异有统计学意义(P<0.01)。在肿瘤组织和癌旁组织中,至少有1种基因发生甲基化的分别为50.9%(54/106)和19.8%(21/106),每个标本的平均甲基化数分别为0.73和0.24,差异有统计学意义(P<0.000 1)。BRCA1基因甲基化与患者的年龄及ER(-)呈显著正相关(P=0.007和0.020);MGMT基因甲基化与乳腺癌分期、组织学分级和淋巴结转移呈显著正相关(P=0.016,0.025和0.030);GSTP1基因甲基化与淋巴结转移、肿瘤大小呈显著正相关(P=0.028和0.033);同时有超过1种基因甲基化与乳腺癌较晚的病理分期及淋巴转移正相关(P=0.028和0.007)。结论：BRCA1、GSTP1和MGMT基因甲基化状况与乳腺癌临床病理特征显著相关,同时存在多个基因甲基化预示着乳腺癌具有侵袭性表型,联合检测3者的甲基化状况可能对乳腺癌预后预测具有重要价值。     

胃癌患者外周血与胃癌组织中BRCA1基因甲基化的关系及其意义

目的:检测胃癌患者外周血及胃癌组织中BRCA1基因启动子甲基化状态,并探讨两者的关系及意义。方法:采用甲基化特异性PCR(methylation-specific polymerase chain reaction,MSP)技术检测37例胃癌患者外周血及胃癌组织中BRCA1基因启动子甲基化状态。结果:胃癌患者外周血和胃癌组织中BRCA1基因启动子甲基化率分别为40.5%(15/37)和48.6%(18/37),二者相关系数r=0.848(P=0.0004)。结论:胃癌患者外周血与胃癌组织中BRCA1基因启动子存在高比例的甲基化,而且两者甲基化率有良好的一致性。胃癌患者外周血BRCA1基因启动子甲基化的检测具有简便、快捷、可靠的特点,外周血BRCA1基因启动子甲基化有可能成为治疗胃癌的靶点。     

胃癌中PCDH8基因启动子甲基化状态及其临床意义

目的:本研究旨在明确胃癌中PCDH8表达水平以及PCDH8基因启动子甲基化情况,分析PCDH8的甲基化差异表达与胃癌临床病理因素的关系。方法:我们通过RT-PCR、Western blot方法检测了65例胃癌组织标本和30例正常胃黏膜标本中PCDH8 mRNA及蛋白的表达,然后分析了其在不同组织中的表达差异。并运用甲基化特异性PCR(MSP)技术检测PCDH8基因启动子区在不同组织中的甲基化情况,并分析其基因启动子区甲基化情况与胃癌临床病理因素的关系。结果:PCDH8 mRNA、蛋白在正常胃组织中为阳性表达,而在胃癌组织中则表达缺失或下调,其差异有统计学意义(P<0.05)。PCDH8甲基化情况在胃癌组织(55.38％,36/65)与正常组织(0％,0/65)、癌旁组织(41.54％,27/65)与正常组织间存在显著差异（P< 0.05)。65例胃癌患者中,其甲基化情况与胃癌患者性别、年龄、肿瘤大小、远处转移及TNM分期均无关(P>0.05)。多因素回归分析结果表明,淋巴结转移为PCDH8基因启动子区甲基化的独立因素(P=0.026,95%CI 1.12~86.84)。结论:PCDH8甲基化及表达情况与胃癌患者肿瘤分化程度及淋巴结转移有关。PCDH8在调节胃癌的发生和转移过程中具有重要作用,它有可能作为胃癌的抑癌基因而发挥作用,并作为标记物对胃癌的诊断、预后判定及治疗提供研究方向。     

Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype. The status of APC gene promoter hypermethylation was investigated in DNA from normal breast tissues, IBC and non-IBC by both conventional and real-time quantitative methylation-specific PCR (MSP). APC methylation levels were compared with APC mRNA and protein levels. Hypermethylation of the APC gene promoter was present in 71% of IBC samples (n=21) and 43% of non-IBC samples (n=30) by conventional MSP (P=0.047). The APC gene also showed an increased frequency of high methylation levels in IBC (in 74% of cases, n=19) vs non-IBC (in 46% of cases, n=35) using a qMSP assay (P=0.048). We observed no significant association between APC methylation levels by qMSP and APC mRNA or protein expression levels. In conclusion, for the first time, we report the association of aberrant methylation of the APC gene promoter with the IBC phenotype, which might be of biological and clinical importance.     

BRCA1基因启动子甲基化在三阴性乳腺癌中的表达及其临床意义

目的:评估三阴性乳腺癌（TNBC）患者中乳腺癌易感基因1（BRCA1）甲基化的表达及与患者预后的关系。方法:收集在我院甲乳科治疗的乳腺癌患者手术切除标本524例,应用联合亚硫酸氢钠限制性内切酶分析法,观察BRCA1启动子甲基化状态。应用定量逆转录聚合酶链反应评估BRCA1 mRNA表达,应用免疫组织化学法评估BRCA1蛋白表达。结果:共有157（30.0%）例TNBC患者,有25（4.77%）例存在BRCA1启动子甲基化,所有BRCA1启动子甲基化的肿瘤均为TNBC。TNBC患者中,BRCA1启动子甲基化患者的BRCA1 mRNA水平显著低于BRCA1启动子未甲基化患者［（0.019±0.005） vs （0.095±0.013）,P<0.001］,免疫组化分析未在BRCA1启动子甲基化患者中检测出BRCA1蛋白表达。BRCA1启动子甲基化患者的总生存率（OS）显著低于非甲基化患者（logrank P=0.038）。BRCA1蛋白低表达患者的OS与RFS均低于高表达组,但差异没有统计学意义（分别logrank P=0.526,P=0.467）。结论:BRCA1启动子甲基化导致了BRCA1表达的下降,并与TNBC患者较差预后相关。BRCA1启动子甲基化是一种促成BRCA1功能丧失的重要机制。     

乳腺癌WIF-1基因表达及其临床病理特征与该基因启动子区域甲基化的关联

  目的  研究WIF-1（Wnt inhibitory factor-1）mRNA在乳腺癌组织中的表达及其启动子区域甲基化情况,进一步探讨WIF-1基因甲基化与乳腺癌临床病理特征的关系。   方法  收集2009年9月1日至2009年12月30日青岛大学附属医院乳腺外科手术切除新鲜组织标本69例,其中良性病变组织9例,乳腺癌及癌旁组织各30例,应用RT-PCR及甲基化特异性PCR（methylation specific PCR,MSP）检测乳腺癌组织、相应癌旁组织和乳腺良性病变组织中WIF-1mRNA表达及其启动子甲基化情况。   结果   癌组织中WIF-1基因表达率明显低于相应癌旁组织及乳腺良性病变组织,具有显著性差异（χ2=41.786,P < 0.05）;与其他两组相比甲基化率在癌组织中明显升高（矫正χ2=16.484,P < 0.05）;WIF-1基因表达下降与其异常甲基化存在明显关联（P=0.023）;WIF-1异常甲基化与乳腺癌发病年龄、肿瘤分级、组织分型和淋巴结转移无相关性（P>0.05）。   结论  异常甲基化可能是乳腺癌WIF-1基因表达下降的重要原因,是乳腺癌发生、发展的重要机制。      

胃癌患者外周血与胃癌组织中ERCC1基因甲基化的关系及其意义

背景与目的：胃癌的发生基于基因和表观遗传学机制,表观遗传学的改变在胃癌的发展中起到重要作用。DNA甲基化是目前研究最多、最为深入的一种表观遗传学表达机制。DNA甲基化是一个可逆性过程。核苷酸切除修复交叉互补基因1(excision repair cross-complementing gene 1,ERCC1)是一种DNA损伤修复基因。本研究检测胃癌患者外周血与胃癌组织中ERCC1基因启动子CpG岛甲基化状态,探讨两者的关系及其意义。方法：采用甲基化特异性PCR技术,检测30例胃癌患者外周血、胃癌组织中ERCC1基因启动子CpG岛甲基化状态。结果：胃癌组织中ERCC1基因启动子CpG岛甲基化率为76.7%(23/30),外周血中ERCC1基因启动子CpG岛甲基化率为63.3%(19/30),差异无统计学意义。结论：胃癌患者外周血中的ERCC1基因启动子CpG岛甲基化率与胃癌组织中相似,检测胃癌患者外周血中的ERCC1基因启动子CpG岛甲基化状态为治疗胃癌提供一个简便、快捷、可靠的途径,同时也为以ERCC1基因启动子CpG岛甲基化作为靶点治疗胃癌提供了可靠的理论依据。     

癌结节在胃癌患者预后中的价值

目的 探讨癌结节在胃癌根治术后患者预后中的价值。方法 收集2015年4月至2016年1月137例胃癌根治术的患者资料,分析癌结节状态与胃癌临床病理特征的关系,并随访患者1年无病生存率。结果 137例胃癌患者的癌结节阳性率为24.8％（34／137）。单因素分析发现,T／N分期越晚、神经／脉管浸润胃癌患者的癌结节阳性率越高。癌结节组与无癌结节组的1年无病生存率分别为59％和85％。对于Ⅰ／Ⅱ期患者,癌结节组和无癌结节组的1年无病生存率分别为40％和91％。结论 胃癌根治术后患者的癌结节与分期、神经／脉管浸润呈正相关。癌结节阳性提示胃癌术后高复发风险,其预后价值在Ⅰ／Ⅱ期胃癌中更显著。     

Reprimo与P16甲基化在胃癌诊断中的价值及其临床意义

目的 探讨胃癌组织中Reprimo与P16基因启动子甲基化在胃癌诊断中的价值及其临床意义.方法 选取68例确诊胃癌患者、50例慢性萎缩性胃炎伴肠上皮化生患者,所有患者均采用内镜取胃黏膜组织进行甲基化检测,对比两组Reprimo与P16基因启动子甲基化阳性率,并探讨其与患者临床病理特征的关系.结果 胃癌组胃黏膜组织标本中Reprimo基因启动子甲基化阳性率为64.71％,明显高于胃炎组的26.00％(P﹤0.01);胃癌组胃黏膜组织标本中P16基因启动子甲基化阳性率为42.65％,高于胃炎组的24.00％(P﹤0.05);胃癌组中发生淋巴结转移、TNM分期为Ⅲ期及Ⅳ期、低分化患者胃黏膜组织标本中Reprimo基因启动子甲基化率高于未发生淋巴结转移、TNM为Ⅰ期及Ⅱ期、高分化和中分化患者(P﹤0.05);不同年龄、性别、癌胚抗原(CEA)水平、肿瘤部位、TNM分期、淋巴结转移情况、分化程度、肿瘤直径的胃癌患者胃癌组织中P16基因启动子甲基化率比较,差异均无统计学意义(P﹥0.05).结论 胃癌组织中Reprimo基因启动子甲基化率明显升高,并且与胃癌的发生发展有关;P16基因启动子甲基化在胃癌组织中甲基化阳性率与胃炎组织相比较,无明显增加.     

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer

Aim： This study explored the correlation between the expression of excision repair cross-complementation group 1 （ERCC1） and the prognosis of gastric cancer patients. Methods： From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry （IHC） was used to assess the expression of ERCCI in resected samples. The relationship between ERCCI expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time （MST） and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. Results： ERCC1 expression was positive in 412 patients （68.1%）. There is no significant difference between ERCCl-positive group and ERCCl-negative group in terms of the MST and 5-year survival rate （P=0.455）. The MST and 5-year survival rate have no significant difference （P=0.162） between group with chemotherapy and group with no chemotherapy in patients with ERCCl-positive expression. However, the MST and 5-year survival rate in patients with ERCCl-negative expression benefited more from with chemotherapy （P=0.019）. The ERCCl-positive patients survived longer than those ERCCl-negative patients （P=0.183） in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC 1 expression had no significant relationship with overall survival in patients with stage II or llI gastric cancer （P〉0.05）. Conclusions： ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCC     

PVT1基因在胃癌患者血液中的表达及其临床意义

目的:检测人浆细胞瘤转化迁移基因1(plasmacytoma variant translocation 1,PVT1)在胃癌患者血液中的表达水平及临床常用肿瘤标志物的含量,探讨PVT1与肿瘤标志物和临床分期分级的关系.方法:采集2015年1月至12月石河子大学医学院一附院收住院的51例胃癌、63例慢性萎缩性胃炎患者与54名正常人外周静脉血,提取血液总RNA.实时定量PCR(qRT-PCR)技术检测血液中PVT1 mRNA表达水平;电化学发光法检测胃癌患者血清中AFP、CEA、CA19-9的含量.结果:PVT1 mRNA在胃癌、慢性萎缩性胃炎患者血液中的表达量较高,胃癌组与正常组相比PVT1 mRNA表达量差异有统计学意义(t=0.000,P＜0.01),慢性萎缩性胃炎组与正常组相比PVT1 mRNA表达量差异也有统计学意义(t=0.000,P＜0.01),但是胃癌患者与慢性萎缩性胃炎患者比较其差异无统计学意义(f =0.459,P＞0.05).PVT1 mRNA表达与淋巴结转移有明显相关(r =0.024,P＜0.05).此外,PVT1 mRNA的表达与血清肿瘤标记物CA19-9具有相关性(r=0.429,P＜0.01).结论:PVT1 mRNA在胃癌、慢性萎缩性胃炎患者血液中表达高于正常人,且与CA19-9具有相关性,提示PVT1 mRNA可能成为胃癌早期诊断及预后的分子标志物之一.     

ONECUT2 基因在人胃癌中的表达及其临床意义

目的：探讨ONECUT2（one cut homeobox 2,OC-2）基因在人胃癌组织中的表达水平及其临床意义。方法：基于生物信息学技术全面检索Oncomine、GEPIA、CCLE、EBI 数据库,分析OC-2 在胃癌和其他种类肿瘤中的表达水平,用Kmplot 数据库验证其表达水平与胃癌患者预后的关系,用STRING数据库构建蛋白互作网络（protein protein interaction network,PPI network）,分析与胃癌相关的OC-2 共表达基因。结果：在OC-2 差异表达的不同种类肿瘤中,其表达水平一般上调。在胃癌组织和细胞中OC-2 表达水平均显著升高（均P<0.05）,且可能与组织分型和肿瘤分期无关（均P>0.05）。OC-2 表达水平与胃癌患者的预后有关,OC-2 低表达组胃癌患者的中位总生存期和中位无病生存期均显著高于高表达组（40.0 vs 26.5 个月,26.2 vs 16.1 个月;均P<0.01）。筛查获得了15 个OC-2 的共表达基因;构建的PPI 网络预测了30 个功能蛋白与OC-2 蛋白相互作用,其中有11 个蛋白基因也与胃癌的发生发展有关,Pearson 相关分析后得出4个与OC-2密切正相关的蛋白基因：PDX1（R=0.49）、CREB1（R=0.31）、MAPK1（R=0.26）、CTSS（R=0.25）。结论：OC-2 在胃癌发生发展及侵袭转移过程中可能起重要的作用,有望成为胃癌诊治和判断预后的重要指标和新的筛查靶点。     

Prognostic significance of cyclin A in gastric cancer

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in > or =5% of the tumor cells was considered the cut-off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the chi2-test, Fisher's exact test, Kaplan-Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279 of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR.