Immune-related long noncoding RNA zinc finger protein 710-AS1-201 promotes the metastasis and invasion of gastric cancer cells

BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

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Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.

Expression of semaphorin 5A and its receptor plexin B3 contributes to invasion and metastasis of gastric carcinoma

AIM:To investigate the protein and mRNA expression of semaphorin 5A and its receptor plexin B3 in gastric carcinoma and explore its role in the invasion and metastasis of gastric carcinoma.METHODS:Expression of semaphorin 5A and its receptor plexin B3 in 48 samples of primary gastric carcinoma,its corresponding non-neoplastic mucosa,and matched regional lymph node metastasis was assayed by reverse transcription-polymerase chain reaction(RT-PCR),real-time RT-PCR and Western blotting.RESULTS:The protein and mRNA expression of semaphorin 5A and its receptor plexin B3 increased gradually in non-neoplastic mucosa,primary gastric carcinoma and lymph node metastasis(P<0.05).Moreover,the expression of semaphorin 5A was closely correlated with that of plexin B3.CONCLUSION:Semaphorin 5A and its receptor plexin B3 play an important role in the invasion and metastasis of gastric carcinoma.

Preliminary study correlating CX3CL1/CX3CR1 expression with gastric carcinoma and gastric carcinoma perineural invasion

AIM:To study the relationship between the CX3CL1chemokine,its receptor CX3CR1,and gastric carcinoma/gastric carcinoma perineural invasion(PNI).METHODS:Thirty cases of gastric carcinoma were surgically resected(radical resection or palliative resection)between February 2012 and July 2012.Tumour and tumour-adjacent tissues were evaluated for the presence of CX3CL1(ELISA)and CX3CR1(immunohistochemistry and Western blotting)in an effort to analyse the relationship between CX3CL1/CX3CR1 and gastric carcinoma/gastric carcinoma PNI.RESULTS:Of these 30 cases,14 were PNI-positive(46.7%).No significant differences in CX3CL and CX3CR1 expression in tumour-adjacent tissues were found between the PNI positive and negative groups.Expression levels of CX3CL and CX3CR1 in tumour tissues were significantly higher than those in adjacent tissues(P<0.01),and were significantly higher in tumour tissues from the PNI-positive group compared to the PNI-negative group(P<0.01).CONCLUSION:CX3CL1/CX3CR1 expression may be associated with the occurrence and development of gastric carcinoma as well as gastric carcinoma PNI.

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM: To investigate the relation of expression transfor-mation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expres-sion of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was nega-tively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, in-vasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in inva-sive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest (51.5%, 17/33). The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was signifi -cantly higher (92.9%) than in tunica muscularis of in-vasive gastric cancer cases, as well as in patients withlymph node metastasis than in those without lymph node metastasis. CONCLUSION: Up-regulation of claudin-1 expres-sion and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo-plasms. Further study is needed to elucidate the pre-cise mechanism and the relation of claudin-1 expres-sion with the neoplasm progress.

Reduction of CAII Expression in Gastric Cancer: Correlation withInvasion and Metastasis

Objective： Human carbonic anhydrases II （CAII） gene plays an important role in different cancer. However, its relevance to gastric cancer （GC） remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. Methods： The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. Results： The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma （100% vs. 63.16% and 28.57%, P0.001）. The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages （70.0% vs. 19.57%, P0.001）. The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases （10.81% vs. 37.33%, P0.05）. Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma （15.94% vs. 31.03% or 60.00%, P0.05）. Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors （P=0.024, log-rank test）. Conclusion： CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.

CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma

AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.

Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis

Objective: To discuss the expression of long noncoding RNA TUG1(lnc RNA-TUG1) in gastric carcinoma(GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. Methods: Forty cases of carcinoma tissue and para-carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lnc RNA-TUG1 in GC and para-C tissues was detected by applying the q RT-PCR technique. The correlation between lnc RNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lnc RNA-TUG1 specific si RNA. Changes of the transferring and invading capacity of si RNAtransfected SGC-7901 cells were scratch-tested and transwell-detected. q RT-PCR was applied to detect the expression level of micro RNA-144 after lnc RNA-TUG1 was silenced. Changes of c-Met m RNA and protein expressions was detected by q RT-PCR and western-blot test. Results: The expression level of lnc RNA-TUG1 in GC tissue was significant higher than that in para-C tissue(P<0.05) and the high expression level of lnc RNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing(P<0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by lnc RNA-TUG1 specific si RNA(P<0.05). The results of q RT-PCR and western-blot proved that the expression of micro RNA-144 was significantly boosted and the expression level of c-Met m RNA and protein was inhibited after lnc RNA-TUG1 was silenced(P<0.05). Conclusions: lnc RNA-TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lnc RNATUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of micro RNA-144/c-Met.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa

AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma

AIM:To explore the syndrome differentiation in traditional Chinese medicine (TCM) and gene protein expression in gastric carcinoma. METHODS:Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin (E-cad) and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method. RESULTS:The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between the different syndrome differentiation types in TCM (P < 0.01). Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types,where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type,where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%,and there was no statistically significant difference between the two groups (χ2= 8.999,P > 0.05). CONCLUSION:E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type,where tumor development and metastasis may be associated with low E-cad expression,or with low homogeneous adhesiveness between tumor cells.

腹腔镜胃癌根治性切除标本cyclin D1和SLeX表达的临床病理研究

目的探讨腹腔镜胃癌根治性切除标本cyclin D1和SLeX表达与患者临床病理特征及预后的关系。方法85例腹腔镜胃癌根治性手术切除标本及30例癌旁胃组织,应用免疫组织化学染色EliVision^(TM)plus二步法检测cyclin D1和SLeX在胃癌及癌旁胃组织中的表达,分析cyclin D1和SLeX与患者性别、癌灶大小、分化程度、临床分期、转移浸润及5年生存期6项临床病理特征的相关性。结果癌组织cyclin D1和SLeX阳性率分别为61.2%(52/85)和85.9%(73/85),癌旁胃组织cyclin D1和SLeX阳性率分别为0和6.7%(2/30),差异均有统计学意义(P<0.05)。Cyclin D1和SLeX表达与性别及癌灶大小无关(P>0.05),在低分化、进展期、有转移浸润和5年内死亡患者中,Cyclin D1和SLeX阳性率均显著高于(高+中)分化、早期、无转移浸润和5年内生存患者(P<0.05)。Cyclin D1和SLeX表达呈正相关(r=0.40)。结论Cyclin D1和SLeX与胃癌发生发展显著相关,两者共阳性表达预示胃癌分化程度低、进展快、易浸润转移、生存期短。

Ets-1和survivin在宫颈鳞状细胞癌中的表达研究

目的 探讨宫颈鳞状细胞癌(宫颈鳞癌)Ets-1和survivin表达与患者临床病理指标的关系。方法应用免疫组化EliVision^(TM) plus二步法检测72例宫颈鳞癌手术标本及30例癌旁宫颈组织Ets-1和survivin表达,分析其表达与患者年龄、癌灶大小、浸润深度、分化等级、TNM分期、术前淋巴转移、术后5年内复发转移7项指标的关系。结果 Ets-1阳性染色可见于细胞核及细胞质,survivin阳性染色多见于细胞质,少见于细胞核。癌组织Ets-1和survivin阳性率(分别为63.9%,72.2%)均显著高于癌旁组织(分别为13.3%,3.3%)(P<0.05)。患者年龄、癌灶大小均与Ets-1和Survivin表达阳性率无关(P>0.05);浸润深度、分化等级、TNM分期、术前淋巴转移、术后5年内复发转移5项指标均与Ets-1和survivin表达阳性率相关(P<0.05)。72例患者Ets-1和survivin共阳率为58.3%,共阴率为22.2%,两者表达呈正相关(r=0.49,P<0.05)。结论 Ets-1和survivin与宫颈鳞癌的发生发展密切相关,两者高水平表达预示癌组织侵袭能力强、分化等级低、病情发展快、淋巴转移早、患者预后差。

ICAM-1蛋白的表达与大肠癌侵袭转移的相关性

目的探讨ICAM-1在大肠癌(colorectal carcinoma,CRC)中的表达与其侵袭转移的关系。方法采用免疫组化SABC法及Western blotting技术检测ICAM-1蛋白在大肠正常黏膜、腺瘤和癌组织中的表达。结果免疫组化结果显示ICAM-1蛋白在CRC和腺瘤的高表达均与正常黏膜的低表达之间的差异有显著性(P<0.001,P<0.001);随着组织分化的降低和Dukes分期的增加,其表达呈上升的趋势;淋巴结和远处器官转移组的表达均高于未转移组(P<0.01,P<0.05)。Western blotting的结果显示ICAM-1的特异性条带出现在Marker标准相对分子量110KD左右,ICAM-1在CRC的阳性率高于正常黏膜的,且差异有显著性(P<0.01)。结论ICAM-1在CRC的表达与其侵袭转移密切相关。

ICAM-1基因K469E与MCP-1基因-2518A/G多态性的交互作用和胃癌侵袭与转移的关系

目的:探讨细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)基因K469E与单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)基因-2518A/G多态性的交互作用和胃癌侵袭与转移的关系。方法:依据TNM分期,选择我院2009年12月至2014年11月收治的胃癌患者4 500例,分为胃癌Ⅰ期组、Ⅱ期组、Ⅲ期组、Ⅳ期组及0期组各900例,各组在年龄、性别、民族、籍贯和生活习惯方面无显著差异,以上述各组患者的外周血白细胞为样本,利用聚合酶链反应(polymerase chain reaction,PCR)技术分析了ICAM-1基因K469E和MCP-1基因-2518A/G多态性。结果:K469E(EE)基因型和-2518A/G(GG)基因型频率在Ⅰ期组、Ⅱ期组、Ⅲ期组、Ⅳ期组与0期对照组之间有显著差异(P<0.01)。K469E(EE)基因型者胃癌侵袭与转移的风险显著增加。-2518A/G(GG)基因型者胃癌侵袭与转移的风险也显著增加。基因突变的协同分析发现K469E(EE)/-2518A/G(GG)基因型者在Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期与0期对照组中的分布频率经χ2检验有显著差异(P<0.01)。K469E(EE)/-2518A/G(GG)基因型者胃癌侵袭与转移的风险显著增加。K469E(EE)和-2518A/G(GG)基因型之间存在超相乘模型的交互作用。结论:K469E(EE)和-2518A/G(GG)基因型均是胃癌侵袭与转移的易患因素,基因多态性的交互作用增加了胃癌侵袭与转移风险。

ICAM-1在乳腺浸润性导管癌中表达情况的初步研究

目的:测定ICAM-1在乳腺浸润性导管癌(IDC)中的表达情况,并探讨其在乳腺IDC进展中的意义。方法:应用免疫组织化学方法研究49例乳腺IDC标本中不同组织成分ICAM-1的表达情况,并统计分析其与淋巴结转移、组织学分级及TNM分期之间的关系。结果:ICAM-1在乳腺IDC癌巢中的表达强度明显低于癌旁正常乳腺导管上皮(P<0.05)及癌间质成分(P<0.05),ICAM-1在乳腺IDC癌巢中的表达阳性率亦明显低于正常乳腺导管上皮(P<0.05)。ICAM-1在乳腺IDC癌巢中的表达阳性率与淋巴结转移呈负相关(rs=-0.312,P<0.05),而与组织学分级及TNM分期无关。结论:ICAM-1的表达水平在乳腺IDC癌巢中与癌旁正常乳腺导管上皮中明显不同,ICAM-1在乳腺IDC中的表达缺失或下调可能更易于肿瘤的淋巴结转移。对ICAM-1的作用机制的深入研究有可能使其成为乳腺IDC患者个体化治疗的新靶点。

NF-κB反义核酸对胰腺癌细胞ICAM-1表达及侵袭转移能力的影响

目的研究核因子-κB(NF-κB)亚单位p65反义寡核苷酸(ASODN)对人胰腺癌细胞细胞间粘附分子-1(ICAM-1)表达及侵袭转移能力的影响。方法设计合成p65ASODN,体外转染人胰腺癌细胞株PANC-1,用流式细胞仪和荧光显微镜检测转染效率,用RT-PCR检测p65及ICAM-1mRNA的表达,用四甲基偶氮唑盐(MTT)法和细胞侵袭实验分析细胞增殖能力和侵袭转移能力的改变。结果p65ASODN可成功转染PANC-1细胞;转染后,p65及ICAM-1mRNA表达明显减弱(P<0.01);细胞增殖活性和侵袭转移能力明显下降(P<0.01)。结论脂质体介导的p65ASODN能有效抑制p65基因的表达,从而降低细胞的侵袭转移能力,p65ASODN可能主要通过下调ICAM-1基因的表达发挥抗侵袭转移的作用。

ICAM-1/LFA-1在结肠癌淋巴转移中表达的研究

目的研究结肠癌瘤体细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)和淋巴细胞功能相关抗原-1(lymphocyte function association antigen-1,LFA-1)的表达与结肠癌临床病理特征及其侵袭转移的关系。方法采用免疫组化技术(S-P 法)对60例结肠癌及15例远癌结肠组织标本中 ICAM-1和 LFA-1进行检测,分析 ICAM-1和 LFA-1的表达与结肠癌临床病理之间的关系。结果结肠癌和远癌结肠组织中 ICAM-1的阳性表达率分别为70%(42/60)和20%(3/15),两者之间差异有显著性(P<0.01),LFA-1的阳性表达率分别为68.3%(41/60)和13.3%(2/15),两者之间差异有显著性(P<0.01),组织 ICAM-1和 LFA-1表达水平与结肠癌淋巴结转移、TNM 分期密切相关。结论检测结肠癌组织 ICAM-1的表达水平对评估淋巴结转移程度、TNM 分期及结肠癌侵袭深度有较大意义,ICAM-1可能是反映结肠癌侵袭转移潜能的一个有效生物学指标。

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Positive association of RhoC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma

Worldwide estimates establish gastric carcinoma as the second most frequent cause of cancer deaths. Tumour invasion and metastasis is the biggest impediment to gastric carcinoma cure. Active migration of tumour cells is now considered as the pivotal step in cancer invasion and metastasis. RhoC is a member of the Ras-superfamily of small guanosine triphosphatases that can regulate many cellular functions, especially cytoskeletal organization and cell locomotion. Overexpressing RhoC in vitro in the poorly metastatic cell line from human melanoma may induce a highly metastatic phenotype.~1 The recent development of laser capture microdissection (LCM) affords the opportunity to further evaluate the role RhoC plays in the invasion and metastasis of gastric carcinoma cells in their native tissue environment.