Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers.

Members of the recently identified family of Homo sapiens Aurora / Ipl1-related kinases (HsAIRKs), homologous to chromosome segregation kinases, fly Aurora and yeast Ipl1, are highly expressed during M phase, and have been suggested to regulate centrosome function, chromosome segregation, and cytokinesis. In the present study, immunohistochemical analyses were performed of HsAIRK1 and HsAIRK3 expression in 78 primary colorectal cancers and 36 colorectal adenomas as well as 15 normal colorectal specimens. In normal colon mucosa, some crypt cells showed weak positive staining in 10 and 12 out of 15 cases for HsAIRK1 and HsAIRK3, respectively, the remaining cases being negative. Elevated expression of HsAIRK1 was observed in 53 (67.9%) of the colorectal cancers, and of HsAIRK3 in 40 (51.3%). Furthermore, colorectal adenomas showed high expression of HsAIRK1 and HsAIRK3 in 11 (30.6%) and 7 (19.4%) cases, respectively, thus being intermediate between colorectal cancers and normal colorectal mucosa. Interestingly, HsAIRK1 overexpression was significantly associated with pT (primary tumor invasion) and p53 accumulation in colorectal cancers. There was no significant correlation between proliferating cell nuclear antigen-labeling index (PCNA-LI) and the levels of these proteins. The results suggest that overexpression of HsAIRK1 and HsAIRK3 might be involved in tumorigenesis and / or progression of colorectal cancers.     

结直肠癌组织中E-钙黏素表达及其临床意义

目的　探讨E -钙黏素在结直肠癌组织中的变化及其与结直肠癌临床病理因素的关系。方法　应用免疫组化方法检测 5 2例结直肠癌、10例结直肠腺瘤、8例正常肠黏膜组织中E -钙黏素的表达情况。结果　结直肠癌E -钙黏素弱表达率或阴性表达率 (3 4.6% ,3 6.6% )明显高于结直肠腺瘤、正常肠组织 (P <0 .0 5 ) ;E -钙黏素表达与结直肠癌远处转移明显相关 (P <0 .0 5 ) ,与肿瘤大小、淋巴结侵犯、浆膜浸润无关 (P >0 .0 5 ) ,低分化者E -钙黏素弱表达率或阴性表达率明显高于中分化、高分化者(P <0 .0 5 ) ,随Duke分期进展 ,E -钙黏素阴性表达率或弱表达率逐渐增高 ,DukeD、C与DukeB、A比较有显著性差异 (P <0 .0 5 )。结论　E -钙黏素与结直肠癌生物学行为密切相关。     

Alternative Splicing of the FHIT Gene in Colorectal Cancers

In the present study, we examined the status of the FHIT gene in 112 colorectal cancer and 137 colorectal adenoma specimens. In a total of 5 specimens (4 colorectal cancers and 1 colorectal adenoma), a common smaller product was detected in addition to the normal size product. This smaller product had lost exon 4, the 5' noncoding region of the FHIT gene, owing to alternative splicing. Moreover, all of the 5 tumors with alternative splicing were located lower on the rectum than the anterior peritoneal reflection.     

bag-1 、bcl-2 在大肠腺瘤和大肠癌中的表达及意义

  目的 探讨抗凋亡基因bag-1、bcl-2在正常大肠黏膜、大肠腺瘤和大肠癌中的表达变化及与大肠癌发生、发展和转移的关系。方法 采用免疫组化SP法，分别检测20例正常大肠黏膜、35例大肠腺瘤和82例大肠癌中bag-1、bcl-2蛋白表达情况。结果 bag-1蛋白在正常肠黏膜、大肠腺瘤、大肠癌中阳性表达率分别为10％、60％、81％。bcl-2蛋白在正常大肠黏膜、大肠腺瘤和大肠癌中阳性表达率分别为25％、80％、65％。大肠腺瘤和大肠癌中bag一1、bcl-2蛋白表达阳性率均显著高于正常大肠黏膜(P<0．05)。bag-1蛋白表达与大肠癌分化程度、Duke‘s分期及淋巴结转移有关(P<0．05)。而bcl-2蛋白表达与性别、年龄、癌肿分化程度、Duke‘s分期及淋巴结转移无关(P>0．05)。结论 bag-1、bcl-2蛋白高表达对大肠癌的发生均起重要作用，而bag-1表达水平与大肠癌的恶性程度有关，可作为预测大肠癌浸润转移潜能的新的生物学指标。     

结直肠肿瘤中端粒酶活性表达及其意义

目的观察端粒酶活性表达与结直肠癌发生及预后的关系。方法应用免疫组织化学法检测48例结直肠癌、19例结直肠腺瘤和11例癌旁正常组织中端粒酶的活性表达,并用统计学方法分析其与结直肠癌临床病理因素间的关系。结果端粒酶在结直肠癌中的阳性率为87.5%,明显高于在19例结直肠腺瘤中的阳性率26.3%（5/19）（P＜0.05）和11例癌旁正常组织中的阳性率0.0%（0/11）（P＜0.01）;且与结直肠癌组织病理学分级、淋巴结转移和临床分期关系密切（P＜0.05）。结论端粒酶表达与结直肠癌的发生呈高度正相关,检测标本中端粒酶活性表达有助于结直肠癌患者的预后评估。     

RCN3 Expression Indicates Prognosis in Colorectal Cancers

Background: Reticulocalbin 3 (RCN3) has been associated with several malignancies. However, its role in colorectal cancer (CRC) remains controversial. Thus, this study aimed to investigate the role of RCN3 in CRC prognosis. Methods: The clinical significance of RCN3 expression in CRC was evaluated in a large cohort of 483 patients. Normal tissues, carcinoma, para-carcinoma, adenoma, and metastatic tissues were evaluated by immunohistochemistry. We investigated the association between RCN3 expression and CRC occurrence in tumors and other tissues. Prognostic factors were also evaluated by Kaplan-Meier survival analysis and the Cox regression model. Results: RCN3 was significantly overexpressed in CRC and metastatic tissues. Patients with high RCN3 expression had shorter disease-free survival than those with low RCN3 expression. Multivariate Cox regression analysis showed a risk ratio HR], 0.607; confidence interval [CI], 0.362–1.016; p < 0.05 after adjusting for other prognostic factors. HighRCN3 expression was also associated with a worse chemotherapeutic response in the colon (p < 0.01) or rectal (p < 0.05) cancer patients who received adjuvant chemotherapy. Conclusion: RCN3 expression level is an independent risk factor and serves as a prognostic biomarker for CRC. High RCN3 expression predicts poor prognosis and chemotherapeutic response.     

Insulin-like Growth Factor-1, IGF-binding Protein-3, C-peptide and Colorectal Cancer: a Case-control Study

Context: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation,and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). Objective: Toexamine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-likegrowth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictivemodels. Materials and Methods: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 andC-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI)statistics were used to assess the discriminatory potential of the models. Results: Serum levels of IGF-1 andIGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01,OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated withrisk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, predictionfor the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 andinverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. Conclusions: The results provide evidence foran association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidatepredictor markers.     

Survivin、caspase-3及AKT1在大肠癌中的表达及意义

目的探讨survivin、caspase-3和AKT1在大肠腺癌中的表达及其临床病理学意义以及三者在大肠腺癌癌变过程中的作用。方法运用免疫组织化学sP法检测58例大肠腺癌、12例大肠腺瘤和10例正常大肠黏膜中survivin、caspase-3和AKT1的表达情况,并分析其与大肠腺癌临床病理特征之间的关系以及三者之间的关系。结果在大肠腺癌中survivin、caspase-3以及AKT1的阳性表达率分别为77．6％（45／58）、32．8％（19／58）及70．7％（41／58）。Survivin在大肠腺癌中的表达高于大肠腺瘤以及正常大肠黏膜（P〈0．05,P〈0．05）,cspase-3在大肠腺癌中的表达低于正常大肠黏膜（P〈0．05）,AKT1在大肠腺癌中的表达高于正常大肠黏膜（P〈0．05）。Survivin的表达与肿瘤分化程度关系密切（P〈0．05）,caspase-3的表达与肿瘤分化程度、淋巴结转移关系密切（P〈0．05,P〈0．05）,AKT1的表达与TNM分期关系密切（P〈0．05）。Survivin的表达与caspase-3的表达呈显著负相关（P〈0．05）,与AKT1的表达呈显著正相关（P〈0．05）。结论Survivin与AKT1在大肠腺癌中高表达,caspase-3在大肠腺癌中低表达,且survivin与caspase-3的表达显著负相关。survivin与AKT1的表达显著正相关,提示survivin可能下调caspase-3的表达而上调AKT1的表达,共同促进大肠腺癌的发生发展。     

基质金属蛋白酶9及其抑制物与大肠癌分期和预后的相关性研究

目的:探讨基质金属蛋白酶9及其抑制物的表达与大肠癌分期和预后的相关性,以期在分子水平上更准确判断患者的预后及寻找相应的基因治疗方法提供依据.方法:采用免疫组化SP法对70例大肠癌术后标本的MMP-9及TIMP-1蛋白进行检测.结果:大肠癌MMP-9和TIMP-1蛋白表达存在显著正相关(r=0.397,P＜0.05).MMP-9蛋白阳性表达在不同Dukes分期、浸润深度及淋巴结转移中的大肠癌有显著性差异(P＜0.05,P＜0.01).TIMp-1蛋白阳性表达在不同的组织学类型及分化程度的大肠癌中存在显著性差异(P＜0.05).不同年龄的大肠癌患者MMP-9和TIMP-1蛋白的表达存在显著性差异(P＜0.05).MMP-9蛋白阳性表达组5年生存率低于阴性组(P＜0.05).结论:大肠癌Dukes C期肿瘤组织中MMP-9蛋白的表达明显高于Dukes A期及B期,肿瘤浸润越深,MMP-9蛋白的表达越高.有淋巴结转移的大肠癌患者MMP-9蛋白阳性表达率明显高于无转移患者.在恶性度较低或分化程度较高的肿瘤组织中,其TIMP-1蛋白的阳性率明显较高.MMP-9蛋白阳性表达患者预后较差.MMP-9可作为预测大肠癌侵袭转移及预后的独立指标.     

Glut-1蛋白在结直肠癌组织中的表达及其临床意义

目的探讨葡萄糖转运蛋白1(Glut-1蛋白)在人结直肠癌组织表达情况及其临床意义。方法应用免疫组化方法检测60例结直肠癌及26例正常肠组织标本中Glut-1蛋白表达水平。结果在正常肠组织中未见Glut-1蛋白的表达,结直肠癌组织中Glut-1蛋白表达率为80.0%。Glut-1蛋白的表达量与结直肠癌分化程度有关(P<0.01)。结论结直肠癌组织中Glut-1蛋白表达水平异常增高在结直肠癌发生、发展中起重要作用,与结直肠癌预后不良有关。     

转化生长因子β1＋915G/C基因多态性与大肠腺瘤及大肠癌的关系

目的探讨转化生长因子β1（TGF-β1）基因＋915位点G/C多态性与大肠腺瘤及大肠癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,检测52例大肠腺瘤、70例大肠癌和102例正常对照者TGF-β1基因＋915位点G/C等位基因及基因型分布,并对该基因多态性与大肠癌临床病理特征之间的关系进行分析。采用酶联免疫吸附试验（ELISA）检测大肠腺瘤、大肠癌和正常对照者血清TGF-β1水平。结果 TGF-β1等位基因频率及基因型频率在病例组和对照组的总体分布无显著性差异。大肠腺瘤组按病变部位分组,大肠癌组按病变部位、分化程度、Dukes分期等临床病理特征分组后,未见TGF-β1＋915位点多态性分布存在显著性差异。大肠腺瘤和大肠癌组血清TGF-β1水平显著高于对照组,但大肠腺瘤和大肠癌组TGF-β1＋915位点各基因型的血清水平无显著性差异。结论 TGF-β1＋915位点多态性与大肠腺瘤及大肠癌无关。TGF-β1＋915位点基因型与血清TGF-β1水平无关。     

FOXO3在结直肠癌组织中的表达及临床意义

目的 探讨叉头框蛋白O3(forkhead box class O3,FOXO3)在结直肠癌(colorectal cancer,CRC)组织中的表达及其临床意义.方法 选择手术切除的结直肠癌标本100份,采用实时定量PCR (real-time quantitative PCR,RT-qPCR)检测结直肠癌组织及相应正常癌旁组织中FOXO3基因mRNA水平表达,采用蛋白免疫印迹法(Western blot,WB)检测上述患者FOXO3蛋白的表达,采用免疫组织化学方法(immunohistochemistry,IHC)检测肠癌组织样本与正常肠粘膜组织FOXO3蛋白的表达.结果 肠癌肿瘤组织中FOXO3 mRNA、蛋白表达水平显著低于远端癌旁组织(P＜0.05);FOXO3阴性组生存率较FOXO3阳性组和FOXO3强阳性组生存率显著降低(P＜0.05);FOXO3强阳性组与FOXO3阳性组生存率比较无明显差异(P＞0.05);FOXO3表达与肿瘤分化(x2=32.7468,P=1.05e-08)、浸润深度(x2=4.0921,P=0.04308)、淋巴结转移(x2=5.7301,P=0.01668)、TNM分期(x2=9.2374,P=0.01451)及组织学分类(x2=8.5963,P=0.01359)密切相关.结论 FOXO3表达可能与结直肠癌的肿瘤分化、浸润深度、淋巴结转移、TNM分期和组织学分类有关.FOXO3表达可能成为判定结直肠癌严重程度及预后效果的预测因子.     

大肠癌组织中EGFR、c-erbB-2、CD44V6和p53异常表达与3年生存率分析

目的：同时检测癌基因EGFR、c-erbB-2、CD44v6和p53在大肠癌组织中的异常表达，分析不同表达水平患者组的3年生存率差异。方法：对63例存档大肠癌石蜡组织标本进行重新切片，分别采用EGFR、c-erbB-2、CD44v6和p53单克隆抗体进行免疫组化染色（SABC法）。所有病例均随访3年以上。结果：全部63例大肠癌中除4例（6．3％）无任何1种癌基因蛋白表达外，11例（17．5％）表达1种癌基因蛋白的患者3年生存率88．8％；19例（30．2％）表达2种癌基因蛋白的患者3年生存率70．5％；15例（23．8％）表达3种癌基因蛋白的患者3年生存率57．8％；14 例（22．2％）表达全部4种癌基因蛋白患者3年生存率22．2％，与前3组患者的3年生存率比较均有显著性差异（P＜0．01）。结论：同时检测大肠癌组织4种癌基因蛋白异常表达可准确判断患者不良预后。     

PD-L1在结直肠癌原发灶中的表达及对肝转移微波消融术后复发的预测价值

目的探讨程序性死亡配体1(PD-L1)在结直肠癌(CRC)肝转移患者原发灶肿瘤细胞(TC)和肿瘤浸润免疫细胞(TIC)中的表达情况,及其对肝转移微波消融(MWA)术后复发的预测价值。方法回顾性收集28例CRC肝转移患者原发灶的石蜡包埋标本,采用免疫组织化学法检测其中PD-L1表达水平,分析其与临床特征的关系。Kaplan-Meier法和Log rank检验进行无复发生存(RFS)分析,Cox比例风险回归模型进行影响复发的多因素分析。结果PD-L1在CRC原发灶TC和TIC中的阳性率分别为14.3%(4/28)和46.4%(13/28)。CRC肝转移患者原发灶TIC的PD-L1表达与肝转移瘤最大径有显著关联(P<0.05),与肝转移MWA术后更差的RFS相关(P<0.05)。CRC肝转移患者原发灶TIC的PD-L1表达、肝转移瘤最大径>3 cm是影响肝转移MWA术后复发的危险因素(P<0.05)。结论CRC肝转移患者原发灶TIC的PD-L1表达可能会增加肝转移MWA术后复发的风险。     

Colorectal Cancers with both p16 and p14 Methylation Show Invasive Characteristics

Recent studies indicated that p16 and p14 inactivation owing to promoter methylation was important for colorectal tumorigenesis. In this study, we examined the methylation status of these genes in 86 primary colorectal cancers using methylation-specific PCR (MSP) and correlated the results with the clinicopathological features of the patients. Aberrant promoter methylation of p16 and p14 genes was detected in 43 of 86 (50%) and 25 of 86 (29%) colorectal cancers, respectively. Next, we examined the correlation of methylation status with the clinicopathological features. We found a significant difference in maximal tumor size ( P =0.022) when patients with both p16 and p14 methylation were compared to other patients. On the other hand, there was no significant difference in other factors, such as the extent of tumor and Dukes stage. These results suggested that colorectal cancer with both p16 and p14 methylation has the same invasiveness at a smaller size compared to that of the cancer with neither p16 nor p14 methylation. Inactivation of both p16 and p14 genes may result in a malignant change in colorectal cancer cells, leading to advanced cancers with a smaller size than those with p16 or p14 activity.     

大肠癌组织中unc5c基因启动子甲基化的分析

目的分析大肠癌(colorectal cancer,CRC)组织中unc5c基因启动子区域甲基化的改变状况及其临床意义。方法运用甲基化特异性PCR技术,检测73例大肠癌患者手术切除的癌组织和相应的癌旁组织及28例正常组织、36例腺瘤患者手术切除的腺瘤组织中unc5c基因启动子区域甲基化的改变情况,并分析与临床病理特征之间的关系。结果73例癌组织样本中甲基化检出率为75％(55/73),相应的癌旁组织为7％(5/73),腺瘤组织为63％(23/36),而正常组织中未检出unc5c基因甲基化。unc5c基因甲基化检出率与年龄、分化程度及TNM分期有关。结论检测unc5c基因启动子区域异常甲基化是大肠癌早期辅助诊断的分子标志物之一。     

Overweight as an Additional Risk Factor for Colorectal Neoplasia in Lean Population

Background: Overweight in Thailand is not as common as in Western countries. We sought to evaluate overweightas the additional risk factor that can increase the prediction of colorectal neoplasia (CRN) detection in Thais apart fromthe Asia-Pacific Colorectal Screening (APCS) score. Methods: We prospectively enrolled asymptomatic 338 subjectswho underwent screening colonoscopy between November 2016 and September 2017. All risk factors according toAPCS, BMI and the presence of metabolic syndrome were collected. Overweight was defined as BMI ≥23 kg/m2. ByAPCS score, subjects were categorized into 1) high-risk and 2) average-risk. Using the combination of APCS scoreand overweight, subjects were stratified into 4 groups; high-risk with overweight (G1), average-risk with overweight(G2), high-risk with normal weight (G3) average-risk and with normal weight (G4). Logistic regression analysis wasused to estimate the risk of detecting CRN. Results: The prevalence of CRN in the high-risk subjects was higherthan that of in the average-risk subjects (49%vs.32%; OR, 2.00; 95%CI, 1.17-3.41). After adjustment for APCS riskfactors and metabolic syndrome, overweight significantly increased the risk of detecting CRN (OR, 2.52; 95%CI,1.57-4.05). Among the 4 groups, the detection rates of CRN were significantly different (G1=64%, G2=40%, G3=32%and G4=21%, p<0.01). The relative risk of detecting CRN increased when G1 (OR 6.49; 95%CI, 2.87-14.67), and G2(2.42; 1.39-4.21) were compared with G4. Conclusions: In addition to the APCS score, overweight is an independentrisk factor for detecting CRN. In Thai population, combining overweight and APCS score may be useful to improvethe prediction for CRN.     

癌蛋白c—erbB—2在大肠癌中表达的意义

探讨癌蛋白ｃ－ｅｒｂＢ－２在大肠部中表达情况及其意义。方法采用免疫组织化学方法检测大肠癌组织中ｃ－ｅｒｂＢ－２蛋白的表达。结果本组７２例大肠癌中有２０例表达ｃ－ｅｒｂＢ－２蛋白,当肿瘤浸润至肠壁外或发生淋巴结或肝脏时,其ｃ－ｅｒｂ－２蛋白阳性性率明显高于无转移或浸润滑未及浆膜的大肠癌。     

大肠癌nm23H1基因表达及其临床意义

目的：研究大肠恶性肿瘤nm23H1基因表达及其临床意义。方法：应用免疫组化SP法检测1990年8月－1996年2月间收治的60例大肠恶性肿瘤。Dusk‘s分期为A期10例,B期25例,C期16例,D期9例。结果：大肠恶性肿瘤nm23H1强阳性23例,中度阳性18例,阴性19例,表达阳性率随分期的进展逐渐下降,有淋巴结转移的表达阳性率明显低于无转移者。结论：抑癌基因nm23H1表达,在大肠癌病期、淋巴结转移和预后研究中可作为判断指标。     

老年大肠腺瘤恶变的临床病理分析

 目的 探讨老年大肠腺瘤恶变及其病理特点。方法 对185例老年大肠脉瘤患者进行分析,观察大肠腺瘤与恶变的关系。结果 老年大肠腺瘤恶变与腺瘤大小、部位、形态、数目、组织学类型及年龄等因素有关,与性别无关。结论 老年大肠腺瘤易恶变,对可疑恶变腺瘤做全瘤切除,术后密切而有规律随访。