淋巴结阳性乳腺癌中的C-MET过表达预后不佳

美国芝加哥大学的林格耶尔(Emst Lengyel)和同事在2月10日《癌症》杂志(Int J Cancer,2005；113：678—682)上报告，对淋巴结阳性的乳癌病人，不管Her-2/neu如何，酪氨酸激酶C—MET过表达与临床预后不佳有关。“将来以C—MET为靶标可能是Her2/neu之外的治疗或补充”。

乳腺癌CIP2A蛋白表达及与预后关系的研究

目的探讨乳腺癌蛋白磷酸酶2A癌性抑制因子(CIP2A)蛋白表达情况及其与患者预后的关系。方法采用免疫组织化学法检测76例乳腺癌患者乳腺癌组织和癌旁组织中CIP2A蛋白的表达情况,并以正常乳腺组织作为对照组。记录患者3年生存状况,分析CIP2A表达情况与生存状况的关系。结果乳腺癌组织中CIP2A表达阳性率显著高于癌旁组织和正常组织(P<0.05),癌旁组织CIP2A表达阳性率显著高于正常组织(P<0.05)。CIP2A蛋白表达阳性与乳腺癌患者组织学分级和病理分期具有相关性,随分级和分期的提高而增加,与患者年龄和肿瘤大小无关。CIP2A表达阳性患者3年疾病无进展率显著低于阴性患者(P<0.05)。结论 CIP2A在乳腺癌发生发展中发挥重要作用,是影响患者预后的重要因素。

E2F-1在肝细胞癌中的表达情况及其对患者预后的影响研究

目的分析E2F-1在肝细胞癌中的表达，探讨E2F-1对患者预后的影响。方法收集2006年1月至2011年12月行根治性切除术的79例肝癌患者的病理标本为研究对象。取距离癌灶〉5cm的癌旁组织30例作为对照。采用免疫组化法检i^qE2F．1的表达情况。对比肿瘤组织与癌旁组织E2F－1的表达差异，分析E2F－1的表达与临床病理参数间的相关性及对术后生存时间的影响。结果79例肿瘤组织中E2F－1阳性表达39例，阳性率为49．4％；30例癌旁组织中未见E2F－1表达。肿瘤组织与癌旁组织中的E2F－1阳性表达率具显著性差异（P〈0．05）。E2F－1的表达与AFP水平、TNM分期及肿瘤直径相关，随着AFP水平的下降，TNM分期的降低及肿瘤直径的减小，E2F－1的表达越高（P〈0．05）；而与患者的年龄、HBsAg感染情况、GGTTZ肿瘤数量等无关（P〉0．05）。E2F－1阳性组总体1、3、5年生存率分别为61．5％、59．0％、46．2％，阴性组总体1、3、5年生存率分别为37．5％、32．5％、17．5％，组间比较E2F－1阳性组总体1、3、5年生存率均高于E2F-1阴性组（P〈0．05）。结论E2F－1在肝癌组织中呈高表达，其表达水平与AFP水平、肿瘤直径及临床分期相关；E2F－1低表达是肝癌术后的总体生存率的独立预后因素，可作为肝癌根治切除术后的独立预后因子。

基于单细胞RNA测序及生物信息学分析AFAP1L1在胃癌中的临床意义

目的分析肌动蛋白丝相关蛋白1相似蛋白1(AFAP1L1)在胃癌(GC)中的预后价值和分子功能。方法基于癌症基因组图谱(TCGA)的大量RNA测序数据,以及来自基因表达综合(GEO)的单细胞RNA测序(scRNA-seq)数据。采用Kaplan-Meier生存分析验证AFAP1L1的预后价值。富集分析探讨AFAP1L1的潜在生物学功能。另外,本研究确定AFAP1L1和抗肿瘤药物敏感性的关系。在单细胞水平上分析AFAP1L1的表达特征。结果AFAP1L1在GC患者中过表达与预后不良相关并参与血管生成的调控。此外,AFAP1L1与达沙替尼和福瑞替尼等抗肿瘤药物的敏感性相关。单细胞RNA测序(scRNA-seq)数据分析显示,AFAP1L1主要表达于GC样本中的内皮细胞中。结论基于生物信息学分析研究结果,AFAP1L1可以作为GC的预后生物标志物。

基于生物信息学分析F2R基因在胃癌中表达与免疫浸润的临床意义

目的探究凝血因子II(凝血酶)受体(F2R)的在胃癌中的表达与免疫细胞浸润情况,探索F2R在胃癌中预后价值及其生物学功能。方法从TCGA数据库中下载胃癌中F2R基因表达谱数据及患者的临床病理信息,使用R4.0.2软件提取F2R在胃癌组及正常对照组的表达量数据,比较两组间F2R的表达差异。利用Kaplan-Meier法分析F2R表达与患者预后的相关性,并利用GEPIA对此进行验证。使用Cox回归分析F2R表达与胃癌患者临床预后相关性。利用GSEA富集分析预测F2R在胃癌中参与的信号通路。使用TIMER2.0分析了F2R表达与免疫浸润之间的关系。结果 F2R在胃癌样本中表达显著上调(P<0.05);生存分析显示F2R高表达组的总体生存率显著高于低表达组,差异均有统计学意义(P<0.05);F2R的表达也与肿瘤组织学分级、临床分期和及肿瘤状态相关,是胃癌的独立预后因素(HR=1.303,95%CI:1.076~1.578,P<0.05)。富集分析结果显示,F2R基因主要富集在MTOR信号通路、MAPK信号通路和癌症通路等。免疫浸润分析结果显示F2R表达与CD4+T细胞、CD8+T细胞、巨噬细胞相关(Rho>0.5,P<0.05)。结论 F2R在胃癌中表达显著上调,可作为胃癌患者的独立预后因子,且与免疫浸润有关。

乳腺癌中c-met蛋白表达的意义

目的研究乳腺癌组织中c－met蛋白表达的意义。方法应用SP免疫组织化学方法对33例乳腺癌石蜡包埋组织作c－met多克隆抗体染色，以10例乳腺纤维腺癌作对照，数据用t检验、X检验和Fisher检验进行统计分析。结果乳腺癌组织中c－met蛋白阳性表达率显著高于对照组（P＜0．01）。c－met蛋白表达与组织学分级、淋巴结转移、临床分期显著相关，而与年龄、绝经状况、肿瘤大小无相关。结论c－met表达是乳腺癌患者重要的预后因素。

雄激素受体(AR)在HER-2过表达型乳腺癌中的作用及机制研究进展

人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)过表达型乳腺癌是乳腺癌中具有侵袭性的亚型之一,与其他类型乳腺癌相比,此类型疾病进展迅速,易复发转移,且预后差。近年来,研究表明雄激素受体(androgen receptor,AR)在HER-2过表达型乳腺癌中高表达。因此,本文将对AR在HER-2过表达型乳腺癌中的作用机制,对预后的影响及最新研究进展进行综述,以期为未来研究提供新的思路。

E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

AIM： To examine the role of E-cadherin and betacatenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas （EBV-GCs）. METHODS： We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients＇ prognosis and the expressions of these proteins. RESULTS： Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 950 confidence interval （CI）, 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs （odds ratio = 2.23; 95% CI, 0.97-5.09）, and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs （P = 0.024）. Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis （P 〈 0.001）. Among EBV- GCs, the depth of invasion （P = 0.005）, lymph node metastasis （P = 0.004） and an intestinal type by Lauren classification （hazard ratio = 9.47; 95% CI, 2.67-33.6） were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC （hazard ratio = 0.32; 95% CI, 0.11-0.93）. CONCLUSION： We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma

AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. RESULTS: The expression rates of abnormal cyclin Dl in gallbladder carcinoma (68.3%)and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3 and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5(33.3% and 38.8%) (P<0.05), and those in pathologic grades G1(54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r= -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin Dl had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). CONCLUSION: Cyclin Dl may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

AIM： To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma （ESCC）. METHODS： Beta-catenin mRNA expression level in 40 ESCC patients （28 males and 12 females, age range 38-82 years, median 60 years） was analyzed by real- time PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker （level 1） or equal to or stronger （level 2） than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS： Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis （0.0776±0.0369 vs 0.3413±0.1803, P 〈 0.001） and deeper tumor invasion （0.0751±0.0356 vs 0.3667±0.1928, P 〈 0.001）, and a poorer survival rate （P = 0.0024） than ESCC with level I expression. CONCLUSION： Beta-catenin expression in ESCC is of great importance.

CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

AIM： To investigate how a complex network of CC chemokine ligands （eeLs） and their receptors influence the progression of tumor and metastasis.METHODS： In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome.RESULTS： We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumornode metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION： These results suggest that overexpression of these two CC chemokine ligands is associ- ated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

Expression and prognostic value of plasminogen activator inhibitor type 1 in node-negative breast cancer

Objective： To investigate the expressions of plasminogen activator inhibitor type 1 （PAl-1）, C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAl-1 in node-negative breast cancer. Methods： The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAl-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months （range 22-117 months）. Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results： High PAl-1 level was positively associated with high histologic grade of the tumors. Disease-free survival （DFS） was significantly shorter for the patients with moderate to intensive expression of PAl-1 than for those with negative （χ^2 = 25.46, P 〈 0.001; χ^2 = 23.07, P 〈 0.001） to mild expression （χ^2 = 19.75, P 〈 0.001; χ^2 = 17.40, P 〈 0.001）. Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAl-1, VEGF and Ki-67 were all significantly prognostic factors for DFS （P 〈 0.05）, PAl-1 was the only independent prognostic factor on multivariate analysis （P 〈 0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928-8.468）. Conclusion： These results of the current study indicate that intermediate or high expression of PAl-1 represents a strong and independent unfavorable prognostic factor for the development of recurrence or metastases in axillary node-negative breast cancer.

Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

AIM： To explore the expression pattern of OCT4 in hu- man esophageal squamous cell carcinoma and its sig- nificance in diagnosis and prognosis.

High expression of △Np73 predicts poor prognosis in NSCLC cancer patients

Objective: To study the expression of △Np73, an isoform of the p53 homologue p73, in the different stages of human non-small-cell lung cancer (NSCLC) and the association of△Np73 expression with in patient survival. Methods: Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to study the expression of△Np73 mRNA in 51 resected NSCLC tissues. Its relation to clinicopathological factors and survival outcome were analyzed. Results: The positive rate and expression level of△Np73 mRNA in the cancer tissues were significantly higher than that in the matched non-cancer lung tissues. The incidence of positive expression of△Np73 was 50. 0% , 52. 6% , and 87. 5% in patients with stageⅠ,Ⅱ, andⅢ, respectively. Positive expression of△Np73 was associated with pathological TNM stage (P = 0. 046), while not with age, gender, histological type and differentiation status. Survival rate of patients with high△Np73 mRNA was significantly poorer than those with low△Np73 mRNA levels (P<0. 001). Multivariate analysis revealed that△Np73 mRNA levels were a significant prognostic factor, independent of the other conventional prognostic factors. Conclusion: NSCLC has over-expression of△Np73 mRNA, which is closely related to TNM stages and prognosis of patients with NSCLC. These results suggest that measurement of△Np73 mRNA levels in tumor tissues might be useful as a promising predictor for the prognosis of patients with NSCLC.

Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis

AIM:To study the risk factors for liver metastasis and the prognosis in patients with human epidermal growth factor receptor 2(HER2) over-expressing gastric cancer(GC).METHODS:A total of 84 GC patients recruited from the General Hospital of the People's Liberation Army(PLA) between 2003 and 2010 were randomly enrolled in this study.HER2 expression was detected by immunohistochemistry in 84 GC patients with liver metastases.The study group consisted of 66 men and 18 women,with an average age of 54 years(range:19-74 years).Liver metastasis was diagnosed by magnetic resonance imaging or computed tomography.Patients were followed-up and predictive factors of liver metastasis were evaluated.RESULTS:The median follow-up period was 47 mo(range:6-85 mo).The characteristics of 35(25.7%) patients with HER2 over-expression of liver metastatic GC are presented.HER2 over-expression was detected in 23 out of 49(46.9%) patients with intestinal GC,and 9 out of 35(25.7%) patients with diffuse GC.29 out of 59(49.2%) patients aged < 60 years were HER2positive,while 8 out of 25(32%) patients aged ≥ 60 were HER2-positive;a significant difference(P < 0.05).Univariate analysis(log-rank test) showed that HER2 over-expression,sex,Lauren classification,differentiation and disease-free interval were correlated with poor survival(P < 0.05).Survival analysis with a survival curve showed that HER2 over-expression was significantly relevant,with a reduced survival time in GC patients with liver metastases(P < 0.01).2-year survival was not associated with the patient's age.A diseasefree survival longer than 12 mo has a significant association with extended overall survival(OS) in GC patients with liver metastases.The median survival time after the diagnosis of liver metastases was 18 mo [95% confidence interval(CI):9.07-26.94] among HER2 positive GC patients with liver metastases.In comparison,for 49(69.4%) out of 84 HER2 negative patients with liver metastatic GC,the median survival time was 47 mo(95% CI:19.37-74.63).In patients with HER2 positive liver metastatic GC,the median OS was significantly shorter than in HER2 negative patients(median,20.32 mo;95% CI:16.51-24.13 vs median,50.14 mo;95% CI:37.83-62.45;P < 0.01).CONCLUSION:HER2 over-expressing GC patients with liver metastases have a poor prognosis.Overall survival was significantly lower in HER2 positive patients.HER2overexpression is correlated with a lower survival rate.

Prognostic significance of PTEN,Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors

AIM:To develop a prognostic approach for gastrointestinal stromal tumors(GISTs) using a cluster of indicators and follow-up information.METHODS:One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location.By immunohistochemistry,the expressions of PTEN,Ki-67,CD44s matrix metalloproteinase(MMP)-9 and TIMP-1 were detected on tissue microarray.Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST.RESULTS:Our data showed small intestinal GIST are more aggressive than gastric GIST.The NIH risk assessment correlated with disease-free survival foreither gastric GIST or small intestinal GIST.Immunohistochemical analysis revealed that Ki-67 labeling indexes(LIs) < 5% predicted higher disease-specific survival(DSS) in gastric and small intestinal GIST.CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST.MMP-9 and TIMP-1 had no correlation with survival.Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST(P = 0.009),as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST(P = 0.011).Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST.CONCLUSION:PTEN LIs ≥ 50%,Ki-67 LIs < 5% and CD44s positivity provides an accurate,favorable prognosis for gastric GIST.PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST.Ki-67 LIs enhances the NIH assessment.

Transcription factor Sp1 expression in gastric cancer and its relationship to long-term prognosis

AIM:To explore the expression of Sp1 in gastric carcinoma as well as its association with other clinicopathologic features, and to evaluate the role of Spl as a prognostic indicator of gastric carcinoma. METHODS: By using immunohistochemistry, we examined the Spl expression patterns in 65 cases of human gastric cancer, and 40 normal gastric mucosa specimens. Simultaneously, the correlation between Spl expression and clinical outcome or clinicopathologic features was investigated. RESULTS: The percentage of Spl expression was 12.5% (5/40) in normal gastric mucosa, and the Spl protein was mainly expressed in the nuclei of cells located in the mucous neck region. In sharp contrast, strong Spl expression was detected in tumor cells, whereas no or faint Spl staining was detected in stromal cells and normal glandular cells surrounding the tumors. The expression rate of Spl in gastric cancer lesions was 53.85% (35/65). The medium survival duration in patients who had a tumor with negative, weak and strong Spl expressions was 1 700, 1 560 and 1 026 d, respectively (P<0.05). Spl protein expression was closely related to the depth of tumor infiltration (X2 = 13.223, P<0.01) and TNM stage (X2= 11.009, P<0.05), but had no relationship with the number of lymph nodes and Lauren's classification (P>0.05). Cox regression model for multivariate analysis revealed that high Spl expression (P<0.05) and advanced stage (P<0.01) were independent predictors of poor survival. CONCLUSION: Normal and malignant gastric tissues have unique Spl expression patterns. Spl might serve as an independent prognostic factor, by influencing the tumor infiltration and progression.

The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E- cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by α-1,6 FucT targeted RNAi and transfecting α-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E- cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after α-1,6 FucT over expression. Our data indicated that α-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asym- metry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

人源OR51E2基因家族全基因组进化和功能分析

短链脂肪酸(SCFAs)是膳食纤维在肠道细菌发酵过程中的代谢产物,主要包括乙酸、丙酸和丁酸,可通过结合SCFAs受体影响宿主健康。OR51E2为一种新发现的SCFAs受体,关于OR51E2的系统发育及其功能研究相对缺乏。利用生物信息学方法分析人源OR51E2基因家族基因的氨基酸组成、保守基序、蛋白结构、理化特性和系统进化关系,利用geneMANIA软件分析OR51E2相互作用蛋白的关系,GEPIA2分析OR51E2在直肠腺癌患者的表达和预后分析。结果表明,人源OR51E2基因家族包含OR51E1、OR51E2两种基因,OR51E1、OR51E2在氨基酸组成、开放阅读框保守基序、蛋白结构整体上基本保守,亮氨酸和色氨酸含量分别为最高和最低的氨基酸,包含三个保守基序,皆为单链氨基酸,但也存在部分差异。系统进化树表明,OR51E2基因家族分为三类,即OR51E1、OR51E2、OR51E2_,进化关系呈水生动物到陆生动物功能结构复杂化。OR51E2在直肠腺癌患者显著性低表达,预后分析显示OR51E2高表达与低表达直肠腺癌患者风险比值为1.5,logrank P=0.38。对OR51E2基因家族全基因组进化和功能分析,为进一步研究OR51E2肠道代谢和疾病调控机制奠定了基础。

Expression of sialyl Lewis^a relates to poor prognosis in cholangiocarcinoma

AIM: High levels of serum sialyl Lewisa (sLea) are frequently found in cholangiocarcinoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study, the clinical significance of sLea expression in CCA tissues and the possible role of sLea in vascular invasion in vitro were elucidated. METHODS: Expression of sLea in tumor tissues of 77 patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry. The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLea expression. RESULTS: sLea was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLea expression and the mass-forming type CCA (P= 0.041), well differentiated histological grading (P=0.029), and vascular invasion (P=0.030). Patients with positive sLea expression had a significantly poorer prognosis (21.28 wk, 95% CI=16.75-25.81 wk) than those negative for sLea (37.30 wk, 95% CI=27.03-47.57 wk) (P<0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLea possessed a 2.3-fold higher risk of death than patients negative for sLea (P<0.001). The role of sLea in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLea, adhered and transmigrated to IL-1β-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLea expression (P<0.001). These processes were significantly diminished when the antibodies specific to either sLea or E-selectin were added to the assays (P<0.001) CONCLUSION: This study demonstrates the clinical significance of sLea expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLea in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies.