Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells

AIM： To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. METHODS： Nuclear matrix proteins were selectively extracted from MGcS0-3 cells treated with or without hexamethylamine bisacetamide （HMBA）, and subjected to 2-D gel electrophoresis. The resulted protein patterns were analyzed by Melanie software. Spots of nuclear matrix proteins differentially expressed were excised and subjected to in situ digestion with trypsin. Peptide masses were obtained by matrix-assisted laser-desorption/ ionization time of flight mass spectrometry （MALDI-TOFMS） analysis and submitted for database searching using Mascot tool. RESULTS： The MGc80-3 cells were induced into differentiation by HMBA. There were 22 protein spots which changed remarkably in the nuclear matrix, from differentiation of MGcS0-3 cells compared to control. Eleven of which were identified. Seven proteinsactin, prohibitin, porin 31HL, heterogeneous nuclear dbonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were downregulated, whereas three proteins - heat shock protein gp96, heat shock protein 90-beta, and valosin-containing protein were upregulated, and the oxygen-regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION： The induced differentiation of carcinoma cells is accompanied by the changes of nuclear matrix proteins. Further characterization of those proteins will show the mechanism of cellular proliferation and differentiation, as well as cancer differentiation.

MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma

BACKGROUND Gastric adenocarcinoma(GAC)mortality rates have remained relatively changed over the past 30 years,and it continues to be one of the leading causes of cancerrelated death.AIM To search for novel miRNAs related to GAC prognosis and further investigate the effect of miR-96-5p on MGC-803 cells.METHODS The miRNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed miRNAs(DEMs)and DEMs related to GAC prognosis.Then,the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR.The target gene,ZDHHC5,of miR-96-5p was predicted using TargetScan,miRTarBase,and miRDB databases and confirmed by luciferase reporter assay.Furthermore,MGC-803 cells were transfected with inhibitor NC,miR-96-5p inhibitor,si-ZDHHC5,or miR-96-5p inhibitor+si-ZDHHC5,and then cell apoptosis was detected by flow cytometry.The expression of ZDHHC5,Bcl-2,and COX-2 was detected using western blotting.RESULTS A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome Atlas.Then compared with adjacent normal samples,the levels of miR-96-5p,miR-222-5p,and miR-652-5p were remarkably increased,while miR-125-5p,miR-145-3p,and miR-379-3p levels were reduced in GAC tumor samples(P<0.01),which were consistent with bioinformatics analysis.Furthermore,ZDHHC5 was defined as a direct target gene of miR-96-5p.miR-96-5p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5,Bcl-2,and COX-2 in MGC-803 cells(P<0.01).After ZDHHC5 inhibition,the number of apoptotic cells and the expression of ZDHHC5,Bcl-2,and COX-2 were reduced.The addition of an miR-96-5p inhibitor partly reversed these effects(P<0.01).CONCLUSION Our findings identified six miRNAs related to GAC prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.

Gastric cardia adenocarcinoma in Taiwan Residents men:Positive associations due to selection bias

The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood.Environmental factors such as Helicobacter pylori(H.pylori) infection and diet have been hypothesized to play a role in the recently increased risk of this disease,but additional studies are needed.In conducting studies to establish the relationship between potential risk factors and gastric cardia adenocarcinoma,it is necessary to carefully consider the role of bias.In a recently published study,the reported associations between H.pylori as well as post-meal physical exertion and gastric cardia adenocarcinoma may have been greatly influenced by selection bias.

Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population

Objective： To investigate the association between gastric cardia adenocarcinoma （GCA） and ten functional single nueleotide polymorphisms （SNPs）, including TPY3BPI rs560191 G〉C, CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A, and six C1 orf 10/CRNN variants. We performed a hospital- based case-control study to evaluate the genetic effects of these SNPs. Methods： Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom- by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results： When the TP^3BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A or the six ClorflO/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conciusions： The results demonstrated that the functional polymorphism TP53BPI rs560191 G〉C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well- designed studies and further functional investigations are needed to confirm our findings.

Pathological factors affecting gastric adenocarcinoma survival in a Caribbean population from 2000-2010

AIM: To investigate pathological factors related to long term patient survival post surgical management of gas-tric adenocarcinoma in a Caribbean population.METHODS: This is a retrospective, observational study of all patients treated surgically for gastric adenocarci-noma from January 1st 2000 to December 31 st 2010 at The University Hospital of the West Indies, an urban Jamaican hospital. Pathological reports of all gastrecto-my specimens post gastric cancer resection during the specified interval were accessed. Patients with a final diagnosis other than adenocarcinoma, as well as pa-tients having undergone surgery at an external institu-tion were excluded. The clinical records of the selected cohort were reviewed. The following variables were analysed; patient gender, patient age, the number of gastrectomies previous performed by the lead surgeon, the gross anatomical location and appearance of the tumour, the histological appearance of the tumour, infil-tration of the tumour into stomach wall and surround-ing structures, presence of Helicobacter pylori and the presence of gastritis. Patient status as dead vs alive was documented for the end of the interval. The effect of the aforementioned factors on patient survival were analysed using Logrank tests, Cox regression models, Ranksum tests, Kruskal-Wallis tests and Kaplan-Meier curves.RESULTS: A total of 79 patients, 36 males and 43 fe-males, were included. Their median age was 67 years(range 36-86 years). Median survival time from surgery was 70 mo with 40.5% of patients dying before the termination date of the study. Tumours ranged from 0.8 cm in size to encompassing the entire stomach speci-men, with a median tumour size of 6 cm. The median number of nodes removed at surgery was 8 with a maximum of 28. The median number of positive lymph nodes found was 2, with a range of 0 to 22. Patients' median survival time was approximately 70 mo, with 40.5% of the patients in this cohort dying before the terminal date. An increase in the incidence of cardiac tumours was noted compared to the previous 10 year interval(7.9% to 9.1%). Patients who had serosal involvement of the tumour did have a significantly shorter survival than those who did not(P = 0.017). A significant increase in the hazard ratio(HR), 2.424, for patients with circumferential tumours was found(P = 0.044). Via Kaplan-Meier estimates, the presence of venous infiltration as well as involvement of the circum-ferential resection margin were found to be poor prog-nostic markers, decreasing survival at 50 mo by 46.2% and 36.3% respectively. The increased HR for venous infiltration, 2.424, trended toward significant(P = 0.055) Age, size of tumour, number of positive nodes found and total number of lymph nodes removed were not useful predictors of survival. It is noted that the results were mostly negative, that is many tumour character-istics did not indicate any evidence of affecting patient survival. The current sample, with 30 observed events(deaths), would have about 30% power to detect a HR of 2.5.CONCLUSION: This study mirrors pathological factors used for gastric cancer prognostication in other popu-lations. As evaluation continues, a larger cohort will strengthen the significance of observed trends.

CHEMOSENSITIVITY OF MGc80-3 HUMAN GASTRIC ADENOCARCINOMA CELLS AND ITS CLINICAL SIGNIFICANCE

In the present study, the chemosensitivity of MGc80-3 human gastric adenocarcinoma cells was determined by means of colony-forming assay and the in vitro activities of 10 anticancer drugs were examined on the basis of the clinically achievable peak plasma drug concentration. The results showed that MGc80-3 cells were most sensitive to mitomyc'n C, adriamycin and 5-fluorouracil, being consistent with the response noted in clinical gastric cancer. This cell line may retain its original drug sensitivity and may be useful in screening for new compounds with activity against this disease.

Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.

Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas

Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

贲门腺癌组织中淋巴细胞活化基因-3的表达及临床意义

目的探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)组织中淋巴细胞活化基因-3(lymphocyte activation gene-3,LAG-3)的表达与临床病理特征和生存期的关系。方法收集2015年1月至2020年12月濮阳市人民医院101例术后病理证实为GCA患者的病理组织蜡块及临床资料,随访其生存状况,采用免疫组织化学方法检测LAG-3的表达情况,采用Kaplan-Meier法及log-rank检验对数据进行分析,并绘制生存曲线。结果LAG-3主要定位在GCA组织的肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)的细胞质和细胞膜上,阳性表达率为53.5%(54/101),LAG-3表达与年龄、性别、大体分型、分化程度、肿瘤直径、浸润深度、淋巴结转移情况、TNM分期无明显相关性(P>0.05);LAG-3阳性组较LAG-3阴性组生存期短(P=0.0099)。结论LAG-3的表达与GCA的临床病理特征之间无明显关联,其阳性表达患者预后差。

信迪利单抗联合奥沙利铂和替吉奥治疗贲门腺癌致免疫性心肌炎并文献分析

报道1例64岁女性患者因贲门腺癌行信迪利单抗(200 mg,d1)+奥沙利铂(200 mg,d1)+替吉奥(60 mg,bid,d1~14)的3周治疗方案。患者在第2周期治疗的第7天出现后背疼痛,心肌损伤标志物升高,心电图Ⅲ、aVF导联可见异常Q波,T波低平。经冠脉CT检查后排除冠状动脉粥样硬化所致冠心病,诊断为免疫性心肌炎。停用抗肿瘤药物,给予甲泼尼龙治疗9 d后症状缓解,心肌损伤标志物明显下降。免疫性心肌炎是信迪利单抗罕见且严重的不良反应,临床应用信迪利单抗时应密切监测心肌损伤标志物的变化和患者的症状、体征。

河南食管癌高发区食管贲门双源癌粘蛋白1、C-erbB2蛋白的表达

目的 :探讨同一个体食管贲门双源癌组织粘蛋白 1(MUC1)和C erbB2蛋白变化的特征及其意义。方法 :采用免疫组化卵白素 生物素 过氧化物酶复合物 (ABC)法和组织病理学方法 ,分析河南食管癌高发区 2 5例双源癌患者 (同时发生食管鳞癌和贲门腺癌 )MUC1和C erbB2蛋白的表达状况。结果 :2 5例患者食管鳞癌和贲门腺癌组织均出现不同程度的MUC1和C erbB2蛋白的阳性表达。食管癌 :MUC1,C erbB2免疫阳性率分别为 80 %(2 0 / 2 5 ) ,2 0 % (5 / 2 5 ) ;贲门癌 :分别为 72 % (18/ 2 5 ) ,4 8% (12 / 2 5 ) ,且免疫反应类型均主要为弥漫型。MUC1,C erbB2蛋白在食管和贲门双源癌肿瘤组织中具有很高的一致性改变 ,一致性改变率分别为 92 %、6 4 %。结论 :食管和贲门双源癌存在较高的MUC1和C erbB2蛋白一致性改变 。

河南食管癌高发区居民食管和贲门上皮癌变过程中C-erbB2和c-myc表达的变化

目的 :探讨河南食管癌高发区居民食管和贲门上皮癌变过程中C erbB2和c myc的表达变化特征及其与病变的关系。方法 :采用纤维内镜活检、组织病理学和免疫组织化学方法 ,对 84例无症状人群食管和贲门粘膜活检组织以及 30例食管鳞癌患者和 30例贲门腺癌患者的癌组织进行C erbB2和c myc的表达变化以及病理学的研究。结果 :5 8例食管粘膜活检组织中 ,共检出 16例正常食管上皮 ,34例基底细胞过度增生 (BCH)和 8例间变(DYS) ;2 6例贲门活检组织中 ,共检出 7例正常 ,6例慢性浅表性胃炎 (CSG) ,10例慢性萎缩性胃炎 (CAG)和 3例DYS。食管正常组织 ,BCH和DYS组织均未发现C erbB2阳性反应 ,但鳞状细胞癌 (SCC)组织C erbB2阳性率为5 0 % ;食管上皮各级病变组织均出现不同程度的c myc阳性反应 ,阳性率随病变进展而明显升高。贲门上皮各级病变组织均出现不同程度的C erbB2和c myc免疫阳性率均出现明显的升高 ,其中间变组织阳性率最高 ,而贲门癌组织中其阳性率略低于间变组织。结论 :c myc过度表达是食管和贲门癌变过程中频发的分子事件 ,并与病变进展密切相关。C erbB2过度表达与贲门上皮癌变密切相关 。

贲门腺癌组织中TSP1高甲基化与TGF-β1及细胞免疫水平的关系

背景与目的:凝血酶敏感蛋白1(thrombospondin-1,TSP1)是一种内源性的血管生成抑制因子,其在肿瘤中的高甲基化可导致其基因沉默。本研究探讨贲门腺癌中TSP1基因的甲基化状态及其与TGF-β1含量及细胞免疫之间的关系。方法:应用甲基化特异性PCR方法和免疫组织化学法分别检测贲门癌组织及相应癌旁组织的TSP1甲基化状况和TSP1蛋白表达情况,ELISA方法检测贲门癌患者血清中TGF-β1的含量,流式细胞术对贲门癌细胞免疫水平进行分析。结果:贲门癌组织TSP1甲基化率为35.4%(34/96),显著高于癌旁组织(3.1%,P<0.01)。Ⅲ期和Ⅳ期贲门癌患者中TSP1基因甲基化率显著高于Ⅰ期和Ⅱ期患者(P<0.05)。贲门癌组织中TSP1的蛋白表达显著低于癌旁组织(P<0.05),且与其甲基化状态之间有明显的相关性。贲门腺癌患者血清中总TGF-β1的含量高于正常对照组(P<0.05),Ⅲ期和Ⅳ期贲门癌患者血清中总TGF-β1的含量显著高于Ⅰ期和Ⅱ期患者(P<0.05),贲门腺癌患者细胞免疫功能低于正常对照,TSP1发生甲基化的贲门癌患者其细胞免疫功能低于未发生甲基化的贲门癌患者(P<0.05)。结论:TSP1基因启动子区的高甲基化可能参与了贲门腺癌的发生发展过程,其高甲基化有可能影响患者的细胞免疫功能。

贲门癌癌组织中环氧合酶-2蛋白的表达

目的检测河南贲门癌高发区贲门癌组织中环氧合酶-2(COX-2)蛋白的表达。方法应用免疫组化ABC方法检测37例贲门癌患者癌组织、癌旁不典型增生组织和正常组织中COX-2蛋白的表达。结果贲门正常组织中COX-2蛋白阳性表达率最低,从正常组(1/30,3%)→不典型增生组(4/16,25%)→贲门癌组(16/30,43%),COX-2蛋白阳性表达率呈逐渐升高趋势(χ2=10.991,P<0.05)。结论COX-2可能在贲门上皮癌变过程中起重要作用。

贲门腺癌组织中RKIP、E-cadherin的表达变化及相关性

目的观察Raf激酶抑制蛋白(RKIP)、上皮型钙黏蛋白(E-cadherin)在贲门腺癌组织中的表达变化,并探讨其相关性。方法应用免疫组化SP法检测160例贲门腺癌组织及癌旁非肿瘤组织中RKIP、E-cadherin的蛋白表达情况,分析其表达与临床病理参数的关系以及两者表达的相关性。结果 RKIP和E-cadherin在贲门腺癌组织中表达明显低于癌旁组织(P均<0.05)。RKIP和E-cadherin在高分化、中分化和低分化的贲门腺癌组织中的表达差异有统计学意义(P均<0.01),在有淋巴结转移的贲门腺癌组织中表达低于无淋巴结转移的组织(P均<0.05)。RKIP和E-cadherin在贲门腺癌组织中的表达呈正相关(r=0.388,P<0.05)。结论 RKIP和E-cadherin在贲门腺癌组织中表达降低,且两者表达呈正相关。

miR-133a-5p对胃贲门腺癌细胞增殖、黏附和M1型巨噬细胞极化的影响

目的:探究miR-133a-5p调控血清外泌体源性纤连蛋白1(fibronectin1,FN1)的表达对胃贲门腺癌(gastric cardia adenocarcinoma,GCA)细胞增殖、黏附和M1型巨噬细胞极化的影响。方法:借助GEO数据库分析GCA组织中的差异表达基因,进行功能富集分析。采用qPCR检测FN1在GCA组织、血清、血清外泌体和细胞中的表达。向GCA患者血清外泌体中转染FN1的过表达载体及其对照质粒,向HGC-27细胞中转染miR-133a-5p模拟物及其对照,将转染后的HGC-27细胞和外泌体共培养,再将此细胞与THP-1细胞共培养。采用CCK-8和细胞黏附实验分别检测各组HGC-27细胞的增殖和黏附情况,WB法、ELISA分别检测细胞中CD86、iNOS的水平以及对巨噬细胞分泌IL-6、IL-1β的影响。采用双荧光素酶报告基因实验验证FN1 mRNA和miR-133a-5p之间的相互作用关系。结果:与健康人对照组相比,GCA组织、血清、血清外泌体和细胞中的FN1表达水平显著上调(均P<0.05),FN1高表达的血清外泌体与GCA患者的TNM分期(P=0.0329)和淋巴结转移有关联(P=0.0127)。富含FN1的血清外泌体能够被GCA细胞内化,与过表达FN1的外泌体共培养能够提高HGC-27细胞的增殖和黏附能力,抑制THP-1细胞中IL-6、IL-1β、CD86和iNOS的表达,抑制M1型巨噬细胞极化(P<0.05或P<0.01)。miR-133a-5p在GCA组织和细胞中较对照组显著降低,可负调控FN1的表达,过表达miR-133a-5p能够通过降低GCA细胞增殖和黏附能力,促进IL-6、IL-1β、CD86和iNOS的表达,部分逆转FN1对GCA细胞恶性行为的促进作用(P<0.05或P<0.01)。结论:miR-133a-5p可通过抑制血清外泌体分泌FN1对GCA细胞的恶性行为起抑制作用,对M1型巨噬细胞极化起促进作用。

凋亡蛋白酶活化因子-1基因在贲门腺癌中的甲基化状态及其临床意义

目的:探讨贲门腺癌(gastric cardiac adenocarcinoma,GCA)中凋亡蛋白酶活化因子-1(apoptosis protease activatingfactor-1,Apaf-1)基因启动子区甲基化状态及其与果蝇zeste基因增强子人类同源物2(enhancer of zeste homolog 2,EZH2)蛋白表达之间的相关性。方法:应用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)检测GCA组织及癌旁组织中Apaf-1基因甲基化状态,应用免疫组织化学法检测GCA组织及癌旁组织中Apaf-1和EZH2蛋白的表达情况。结果:GCA组织中Apaf-1基因甲基化率显著高于癌旁组织[49.6%(62/125)vs 4.0%(5/125),P<0.01],Ⅲ期和Ⅳ期GCA组织中Apaf-1基因甲基化率显著高于Ⅰ期和Ⅱ期(58.8%vs 38.6%,P<0.05),但GCA组织中Apaf-1基因甲基化率与GCA的组织学分化程度无关(P>0.05)。GCA组织中Apaf-1蛋白表达阳性率显著低于相应癌旁组织(39.2%vs 96.0%,P<0.01),且与Apaf-1基因甲基化状态相关。GCA组织中EZH2蛋白表达阳性率显著高于相应癌旁组织(74.4%vs 11.2%,P<0.01),且与Apaf-1蛋白的表达呈负相关。结论:GCA组织中Apaf-1基因启动子区呈高甲基化,Apaf-1和EZH2蛋白可能共同参与了GCA的发展。

25年来经胃镜检出胃癌的变化趋势-1178例临床流行病学分析

目的 根据我院经内镜检出并经病理确诊胃癌的临床病理资料 ,对其临床流行病学特点进行探讨。方法 选择 1975年 1月至 1999年 12月来我院进行胃镜检查并经病理确诊的胃癌患者 ,对其主要的临床症状、内镜下表现及病理组织学特点进行调查。病理学Warthin starry染色阳性为幽门螺杆菌感染诊断标准。结果 2 5年来胃镜胃癌的总检出率为 1.95 % (1178/ 6 1475 ) ,其中早期胃癌 48例 ,占 4.1%。 46 6例进行了HP的检测 ,阳性 147例 ,阳性率 31.5 %。 2 5年来每年胃癌的检出率无明显下降趋势。 2 5年来每年胃贲门癌的构成虽有一些波动 ,但无上升趋势。青年组 (≤ 35岁 )胃癌女性占 5 8.9% ,胃窦部癌占 73.3% ,胃贲门癌占 7%。老年组 (≥ 6 0岁 )胃癌女性占 19.5 % ,胃窦部癌占 44 .5 % ,胃贲门部癌占 42 .5 %。两组比较存在显著性差异 (P <0 .0 5 )。结论 我国常规胃镜检查的早期胃癌的诊断率很低 ,2 5年来胃癌的检出率、胃贲门癌的发生率无明显下降和升高趋势。