微小RNA-185水平对结直肠癌术后无进展生存有评估价值

摘要 目的: 探讨微小RNA(miRNA)-185表达与结直肠癌临床病理特点的关联及其对预后的评估价值。方法： 回顾性分析手术治疗的130例结直肠癌患者的临床资料,使用荧光定量聚合酶链反应（PCR）技术检测癌组织标本和癌旁正常组织中的miRNA-185表达水平,分析不同临床病理资料特征下miRNA-185表达水平差异。通过受试者工作特征（ROC）曲线和Cox多因素回归分析miRNA-185对预后的评估价值。结果： 结直肠癌组织中miRNA-185水平低于癌旁正常组织（0.176±0.085 vs 0.364±0.113,P<0.05）,不同性别、年龄、分化程度、肿瘤位置和肿瘤大小特征下miRNA-185表达水平无统计学差异（P均>0.05）,miRNA-185在Ⅲ~Ⅳ期结直肠癌、淋巴结转移肿瘤组织中表达水平更低（P均<0.05）。对评估术后肿瘤是否进展进行ROC曲线分析显示,miRNA-185的曲线下面积为0.816,95%CI：0.716~0.923,灵敏度为70.21%,特异性为83.23%,多因素Cox结果显示,TNM分期为Ⅲ~Ⅳ期 (HR=2.417, 95%CI:1.362~4.289),miRNA-185低表达(HR=3.121, 95%CI：1.603~6.077)是预后的危险因素。结论： miRNA-185在结直肠癌组织中表达水平下调,并能作为潜在的评估结直肠癌术后无进展生存的标志物。     

结直肠癌AIM2和血清CEA表达水平及其临床意义

目的探讨结直肠癌患者黑色素瘤缺乏因子2（AIM2）和血清癌胚抗原（CEA）表达水平及其临床意义。 方法收集辽宁省肿瘤医院2010年1月~2013年3月118例结直肠癌患者的肿瘤组织标本及其50例癌旁正常组织标本,采用免疫组织化学法测定组织中AIM2的表达,回顾性搜集患者临床病理参数及术前通过电化学发光法（ECUA）测定的血清CEA水平。通过相关性分析癌组织中AIM2表达水平和血清CEA水平的相关性,分析两种指标与临床病理参数的关系。采用Kaplan-Meier法对不同AIM2、CEA水平组别进行生存分析。 结果118例肿瘤组织中有42例AIM2呈高表达,有39例癌旁正常组织呈高表达,差异具有统计学意义（χ²=25.295,P<0.001）;结直肠癌患者术前血清CEA阳性率为44.07%（52/118）。Spearman等级相关性分析结果显示,结直肠癌组织AIM2和血清CEA表达呈负相关（r=-0.660,P<0.001）。肿瘤的浸润深度、TNM分期以及淋巴结转移是影响癌组织AIM2表达水平的相关因素（χ²=4.847,7.794,3.961;均P<0.05）;肿瘤大小、TNM分期以及分化程度是影响患者术前血清CEA水平的相关因素（χ²=17.14,5.779,5.293;均P<0.05）。K-M生存分析显示,AIM2高表达组生存时间明显长于低表达组,术前CEA阴性组生存时间明显长于阳性组,AIM2高表达联合CEA阴性患者生存时间明显长于AIM2低表达联合CEA阳性患者,差异具有统计学意义。 结论结直肠癌患者AIM2和血清CEA表达可能与结直肠癌的进展有关,联合分析两个指标有助于评估结直肠癌患者预后。     

结直肠癌组织中Tob mRNA的表达变化

用荧光定量RT-PCR技术检测76例结直肠癌组织及其相应癌旁正常组织中的Tob mRNA。结果显示,癌组织Tob mRNA的表达高于癌旁正常组织（P〈0.05）;Tob mRNA表达随着结直肠Duke分期的进展有增加趋势（P〈0.05）。认为在结直肠癌的发病中,Tob基因可能发挥致癌基因的作用。     

CKS2在结直肠癌中的表达和临床意义

背景：细胞周期蛋白依赖性激酶亚基（CKS）家族在细胞周期调节中起重要作用。研究发现其家族成员CKS2在一些恶性肿瘤中呈高表达,并与肿瘤的高侵袭性行为和预后不良相关。目前关于CKS2与结直肠癌关系的文献报道较罕见。目的：研究CKS2在结直肠癌中的表达和临床意义。方法：应用realtimeliT—PCR和蛋白质印迹法检测23例临床结直肠癌手术标本癌组织、癌旁非癌组织和正常组织中的CKS2mRNA和蛋白表达。结果：CKS2mRNA和蛋白在结直肠组织中的相对表达量依次为：癌组织〉癌旁组织〉正常组织,癌组织与正常组织问差异有统计学意义（P〈0．01）。性别对CKS2mRNA在不同结直肠组织中的表达趋势无明显影响。癌组织中的CKS2蛋白表达与肿瘤大小和pTNM分期呈正相关（P〈0．01）,与肿瘤部位无关。结论：CKS2蛋白在结直肠癌中呈高表达并与肿瘤临床病理特征相关,有望成为结直肠癌新的分子标记物和治疗靶点。     

Nup88在结直肠癌组织中的表达及意义

目的研究核孔蛋白复合体蛋白88（Nup88）蛋白和mRNA在结直肠癌组织中的表达及其与临床病理特征的关系。方法免疫组化方法检测181例结直肠癌标本、18例淋巴结转移癌及84例匹配的癌旁无瘤黏膜组织中Nup88蛋白表达;RT-PCR法检测Nup88 mRNA在29例结直肠癌标本及配对的癌旁2 cm组织、切缘黏膜中的表达水平。结果结直肠癌组织和淋巴结转移癌中Nup88蛋白阳性率均高于癌旁无瘤黏膜组织（P〈0.01）;Nup88蛋白的表达与结直肠癌组织分化程度有关。Nup88 mRNA在肿瘤组织中的表达水平高于癌旁无瘤黏膜和切缘黏膜（P均〈0.01）。结论 Nup88蛋白及mRNA与结直肠癌的发生发展有关,其蛋白表达可作为评估结直肠癌生物学行为的指标之一。     

结直肠癌组织中VEGF、PINCH mRNA的表达变化及意义

目的观察结直肠癌组织中VEGF、PINCH mRNA的表达变化,探讨其在结直肠癌发生、发展中的作用。方法采用RT-PCR法检测40例结直肠癌组织、配对的癌旁无瘤黏膜组织、手术近端及远端切缘正常黏膜组织中的VEGF、PINCH mRNA。结果结直肠癌组织中VEGF、PINCH mRNA的表达量分别为0.975±0.397、0.772±0.591;癌旁无瘤黏膜组织中分别为0.351±0.255、0.494±0.327;近端切缘黏膜中分别为0.441±0.360、0.518±0.298;远端切缘黏膜中分为为0.423±0.248、0.488±0.335,P均〈0.01。结直肠癌组织中VEGF mRNA的表达与组织学分级、浸润深度及淋巴结转移密切相关（P均〈0.05）,PINCH mRNA表达与组织类型有关（P〈0.05）;结直肠癌组织中VEGF mRNA的表达与PINCH mRNA的表达呈显著正相关（r=0.431,P=0.022）。结论结直肠癌组织中VEGF、PINCH mRNA的表达上调。VEGF和PINCH mRNA与结直肠癌的发生、发展及转移密切相关。     

结直肠癌组织COX-2 mRNA表达的临床病理意义

目的检测环氧合酶-2(COX-2)mRNA在结直肠癌、癌旁及正常组织中的表达情况.探讨其表达与临床病理特征的关系.方法应用逆转录聚合酶链反应(RT-PCR)技术检测24例结直肠癌、癌旁和正常组织中COX-2的mRNA表达.结果 24例结直肠癌中,COX-2 mRNA表达阳性者17例,癌旁和正常组织阳性者分别为9例和3例,癌组织中的表达率明显高于癌旁和正常组织(P＜0.01);COX-2 mRNA的阳性表达与结直肠癌的淋巴结转移、远处转移、Duke′s分期呈正相关.结论结直肠癌组织中COX-2 mRNA表达水平高于癌旁和正常组织,其表达与结直肠癌侵袭转移密切相关.因此COX-2mRNA可作为预测结直肠癌细胞转移潜能的敏感指标.     

FBXO5在结直肠癌中的表达及临床意义

目的探讨FBXO5在结直肠癌中的表达及临床意义。方法采用RT-PCR和Western blot方法检测癌和癌旁组织配对的结直肠癌临床标本中的FBXO5 mRNA和蛋白的表达水平,采用免疫组织化学技术检测240例石蜡包埋的结直肠癌标本,统计学分析FBXO5表达与临床病理学指标、预后的关系。结果与相应配对的癌旁组织相比,癌组织标本中FBXO5 mRNA和蛋白明显上调。统计学分析结果显示,FBXO5表达与结直肠癌患者的临床病理特征密切相关:临床分期(P=0. 004),T分期(P=0. 009),M分期(P=0. 003)。进一步的多因素分析显示,FBXO5表达可作为结直肠癌独立的预后因素(P=0. 045,HR 1. 53,95%CI 1. 01～2. 31)。结论 FBXO5在结直肠癌中表达升高预示结直肠癌患者的不良预后。FBXO5可以成为判断结直肠癌预后的一个新指标。     

结直肠癌组织中RhoC mRNA的表达及意义

目的 观察RhoC mRNA在结直肠癌组织中的表达变化,探讨RhoC mRNA的表达在结直肠癌发生、发展和侵袭转移中的作用.方法 实时荧光定量PCR(FQ-PCR)检测RhoC mRNA在结直肠癌、癌旁组织及大肠正常黏膜中的表达及其与结直肠癌临床病理学指标的关系.结果 RhoC mRNA在结直肠癌组织中的表达较癌旁组织及正常黏膜组织明显增高(P<0.05).RhoC mRNA的表达与结直肠癌的淋巴结转移、肝转移及肠壁浸润深度有关(P<0.05).结论 RhoC mRNA表达与结直肠癌的发生、发展和侵袭转移密切相关.     

整合素β3表达与结直肠癌淋巴结转移的相关性

目的探讨结直肠癌患者肺转移重要的血管内皮细胞标志物整合素β3（ITGB3）表达与结直肠癌转移之间的相关性。 方法采用免疫组织化学染色法检测49例原发性结直肠癌患者癌组织、癌旁正常肠黏膜组织以及相应淋巴结组织中ITGB3的表达。其中37例患者有淋巴结转移。分析ITGB3表达与患者结直肠癌转移的相关性。 结果免疫组化染色结果显示,ITGB3主要在原发性结直肠癌组织、癌旁正常肠黏膜细胞质以及相应淋巴结的间质中表达。ITGB3在不同组织的表达不同,在癌组织中的表达低于癌旁正常肠黏膜组织,且差异有统计学意义（P<0.01）;有淋巴结转移患者淋巴结ITGB3表达高于无淋巴结转移患者,且差异有统计学意义（P<0.001）。淋巴结上皮细胞ITGB3的表达与淋巴结间质组织的表达呈正相关（r=0.395,P=0.005）;且有淋巴结转移患者癌组织上皮细胞ITGB3表达与淋巴结上皮细胞ITGB3表达呈正相关（r=0.514,P=0.001）。ITGB3在淋巴结表达、上皮细胞表达以及间质表达均与淋巴结转移呈正相关（r=0.659,P<0.0001;r=0.661,P<0.0001;r=0.354,P=0.013）。 结论ITGB3淋巴结表达与结直肠癌淋巴结转移呈正相关。ITGB3可能是原发性结直肠癌患者淋巴结转移的潜在分子标志物。     

Tissue microarray for high-throughput analysis of gene expression profiles in hepatocellular carcinoma

AIM: To study the expression profiles of HBsAg, HBcAg, p21WAF1/CIP1 (p21), Rb genes in hepatocellular carcinoma (HCC) and to investigate their roles in the hepatocar-cinogenesis. METHODS: HCC tissue microarray containing 120-min tissues of 40 HCC cases was constructed. HBsAg, HBcAg, p21 and Rb proteins were immunohistochemically stained by streptavidin-peroxidase conjugated method (S-P). The expression loss of these genes in cancerous, para-cancerous tissues and adjacent normal liver tissues of 40 HCCs were comparatively examined. RESULTS: The positive rate of HBsAg expression in cancerous tissues of 40 HCCs was 7.5%, which was lower than that in para-cancerous and adjacent normal liver tissues (X2=12.774, P<0.01; X2=18.442, P<0.01). The positive rate of HBcAg expression in cancerous tissues of 40 HCCs was 20.0%, which was also lower than that in para-cancerous and adjacent normal liver tissues (X2=9.482, P<0.01; X2=14.645, P<0.01). p21 protein deletion rate in cancerous tissues of 40 HCCs was 27.5%, which was higher than that in para-cancerous and adjacent normal liver tissues (X2=7.439, P<0.01; X2=11.174, P<0.01). p21 protein deletion correlated remarkably with the pathological grade of HCC (X2=0.072, P<0.05). Rb protein deletion rate in cancerous tissues of 40 HCCs was 42.5%, which was also higher than that in para-cancerous and adjacent normal liver tissues (X2=10.551, P<0.01; X2=18.353, P<0.01). Rb protein deletion rate did not correlate remarkably with tumor size or pathological grade of HCC (X2=0.014, P>0.05; X2=0.017, P>0.05). CONCLUSION: Expression deletion of HBsAg, HBcAg, p21 and Rb proteins in HCCs may play important roles in the carcinogenesis of HCC. Tissue microarray is an effective high-throughput technique platform for cancer research.     

15-LOX-1蛋白在大肠癌中的表达及临床意义

目的探讨15-LOX-1蛋白表达与大肠癌临床病理因素和患者预后的关系,并探索其可能的作用机制。方法采用免疫组化SP法,检测15-LOX-1蛋白在103例大肠癌组织、56例大肠癌癌旁正常组织中的表达,结合患者的临床病理因素、预后情况及大肠癌组织中其他与侵袭转移相关的指标进行分析。结果 15-LOX-1蛋白在大肠癌组织中的阳性表达率显著低于大肠癌癌旁正常组织(P<0.05);15-LOX-1蛋白的表达与大肠癌的组织病理类型、淋巴结转移、其他器官侵袭转移以及Dukes分期密切相关(P<0.05),病理分化程度低、Dukes分期晚以及有淋巴结或其他器官侵袭转移者肠癌组织中15-LOX-1蛋白表达水平降低;大肠癌组织中15-LOX-1阳性表达患者1年、3年、5年生存率及中位生存时间明显高于15-LOX-1阴性表达患者(P<0.05),多因素COX回归分析结果提示15-LOX-1表达水平、患者年龄及手术时有无淋巴结转移可以作为评估大肠癌患者预后的独立因素(P<0.05);大肠癌中15-LOX-1与VEGF、MMP-2、MMP-7的表达均呈负相关(P<0.05)。结论 15-LOX-1对大肠癌具有抑癌作用,对反映大肠癌生物学行为和判断预后有重要意义。     

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM: To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma.METHODS: Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma.RESULTS: The survivin positive unit (PU) was higher in cancerous tissues (38.76±5.14)than in para-cancerous (25.17±7.26) or normal tissues (0.57±0.03) (P<0.05).The apoptosis index (AI) of para-cancerous tissues was(7.51±2.63%) higher than cancerous tissues (4.65±1.76%).The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma.CONCLUSION: Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.     

结直肠癌组织HHLA2、 TMIGD2表达及其临床病理意义

目的 探讨结直肠癌组织中人内源性逆转录病毒-H长末端重复关联蛋白2(HHLA2)、跨膜和免疫球蛋白结构域2(TMIGD2)表达及其与患者临床病理特征及预后的关系.方法 选取2016年10月至2017年10月于北京老年医院住院治疗的168例结直肠癌患者(结直肠癌组);选取结直肠癌患者相应癌旁正常组织作为对照组.采用免疫组...     

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM: To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS: Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS: The survivin positive unit (PU) was higher in cancerous tissues (38.76±5.14) than in para-cancerous (25.17±7.26) or normal tissues (0.57±0.03) (P<0.05). The apoptosis index (AI) of para-cancerous tissues was (7.51±2.63%) higher than cancerous tissues (4.65±1.76%). The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION: Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.     

miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer

AIM: To determine the expression of miR-422a in colorectal cancer (CRC) tissues and to further explore the prognostic value and function of miR-422a in CRC carcinogenesis.METHODS: miR-422a expression was analyzed in 102 CRC tissues and paired normal mucosa adjacent to carcinoma by quantitative real-time PCR. The relationship of miR-422a expression with clinicopathological parameters was also analyzed. Kaplan-Meier analysis and Cox multivariate analysis were performed to estimate the potential role of miR-422a. Cell proliferation, migration, and invasion were used for in vitro functional analysis of miR-422a.RESULTS: The levels of miR-422a were dramatically reduced in CRC tissues compared with normal mucosa (P < 0.05), and significantly correlated with local invasion (P = 0.004) and lymph node metastasis (P < 0.001). Kaplan-Meier survival and Cox regression multivariate analyses revealed that miR-422a expression (HR = 0.568, P = 0.015) and clinical TNM stage (HR = 2.942, P = 0.003) were independent prognostic factors for overall survival in CRC patients. Furthermore, in vitro experiments showed that overexpression of miR-422a inhibited the proliferation, migration, and invasion of SW480 and HT-29 cells.CONCLUSION: Down-regulation of miR-422a may serve as an independent prognosis factor in CRC. MiR-422a functions as a tumor suppressor and regulates progression of CRC.     

Slug和E-cadherin在结直肠癌组织中的表达及临床意义

目的探讨Slug和E-cadherin在结直肠癌组织中的表达及预后意义。方法应用免疫组化SP法检测65例结直肠癌组织,25例癌旁正常结直肠组织中Slug和E-cadherin的表达,分析两者表达水平与临床病理特征及患者预后的关系。结果 Slug在结直肠癌组织中异常表达率为47.1%,而在正常结直肠组织中表达率为12%,差异有统计学意义(P<0.01);E-cadherin在结直肠癌组织中异常表达率为55.4%,而在正常结直肠组织中表达率为8%,差异有统计学意义(P<0.01);两者阳性表达率与肿瘤浸润深度、分化程度、淋巴结转移、Dukes分期相关性均有统计学意义(P<0.05)。Slug、E-cadherin、淋巴结转移、Dukes分期可成为影响结直肠癌预后的独立因素(P<0.05)。结论 Slug和E-cadherin的表达异常可能与结直肠癌的发生发展、转移相关并可作为评价结直肠癌生物学行为和预后的重要指标。     

结直肠癌患者组织中miR-99a和miR-100表达水平与肿瘤转移的关系

目的 探讨结直肠癌组织中miR-99a、miR-100的表达水平与肿瘤转移的关系.方法 收集2014年1月至2019年1月台州市第一人民医院收治的84例行手术治疗的结直肠癌患者的肿瘤组织、癌旁组织和正常组织标本,采用实时荧光定量PCR法检测各组织中miR-99a、miR-100的表达水平,收集患者的临床病理参数及随访情...     

Prognostic value of c-Met in colorectal cancer:A metaanalysis

AIM: To assess the prognostic value of c-Met status in colorectal cancer. METHODS: We conducted a search in Pub Med, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0.RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios(HR)indicated that patients with high c-Met expression have a significantly poorer overall survival(OR)(HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival(PFS)(HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported(HR = 1.41, 95%CI: 1.08-1.74).CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.     

Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients

AIM: To investigate microRNA-133a (miR-133a) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis.METHODS: Quantitative real-time polymerase chain reaction was used to measure levels of miR-133a in tumor samples and adjacent non-cancerous tissues from 169 patients undergoing radical resection for CRC. The associations between miR-133a expression and patient age, sex, as well as clinicopathologic parameters, such as tumor size, differentiation, location, invasion depth, metastasis, tumor-node-metastasis (TNM) stage and overall patient survival, were analyzed by Mann-Whitney U and Kruskal-Wallis tests. The Kaplan-Meier method and Cox proportional hazards regression analyses were performed to estimate the prognostic factors for patient survival prediction.RESULTS: The expression of miR-133a was significantly downregulated in CRC tissues compared with adjacent non-cancerous tissues (P < 0.05). This reduction was associated with the depth of the local invasion, poor differentiation, lymph node metastasis and advanced disease (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-133a expression had poorer overall survival (OS) than those with high miR-133a expression (P < 0.001). Univariate analysis revealed statistically significant correlations between OS and miR-133a level, tumor local invasion, lymph node metastasis and TNM stage (P < 0.001). Furthermore, miR-133a levels and TNM stage were independently associated with OS (HR = 0.590, 95%CI: 0.350-0.995, P < 0.05; and HR = 6.111, 95%CI: 1.029-36.278, P < 0.05, respectively).CONCLUSION: The downregulation of miR-133a may play an important role in the progression of CRC and can be used as an independent factor to determine CRC prognosis.