胃癌患者血清PGⅠ/PGⅡ、TK1、CEA水平变化与预后的关系

目的 探讨胃癌患者血清胃蛋白酶原Ⅰ/胃蛋白酶原Ⅱ(PGⅠ/PGⅡ)比值、胸苷激酶1(TK1)、癌胚抗原(CEA)水平变化与预后的关系。方法 选取2015年8月至2017年2月治疗的胃癌患者106例为胃癌组,以同期良性胃部疾病患者92例为对照组。比较胃癌组及对照组、早期胃癌及进展期胃癌患者血清PGⅠ/PGⅡ、TK1、CEA水平;采用入组后5年生存情况将胃癌组分为生存组和死亡组,比较2组血清PGⅠ/PGⅡ、TK1、CEA水平,分析联合检测对胃癌生存情况的评估价值,分析各指标与胃癌患者生存期的相关性。结果 胃癌组PGⅠ水平低于对照组,PGⅡ、TK1、CEA水平高于对照组,PGⅠ/PGⅡ值小于对照组(P<0.05);进展性胃癌患者PGⅠ水平低于早期胃癌患者,PGⅡ、TK1、CEA水平高于早期胃癌患者,PGⅠ/PGⅡ值小于早期胃癌患者(P<0.05);腺癌及印戒细胞癌的PGI、PGⅡ、TK1、CEA水平及PGⅠ/PGⅡ值对比差异无统计学意义(P>0.05);生存组PGⅠ水平高于死亡组,PGⅡ、TK1、CEA水平低于死亡组,PGⅠ/PGⅡ值大于死亡组(P<0.05);PGⅠ/PGⅡ比值及TK1、CEA水平联合检测预测胃癌生存情况的AUC>0.75;PGⅠ/PGⅡ比值≥1.68患者的5年累积生存率高于PGⅠ/PGⅡ比值<1.68患者,CEA≥4.35 ng/ml患者5年累积生存率低于CEA<4.35 ng/ml患者(P<0.05);不同TK1水平患者的5年累积生存率对比无明显差异(P>0.05);死亡组中TNM分期为Ⅲ~Ⅳ期、淋巴结转移、PGⅠ/PGⅡ比值<1.68、CEA≥4.35 ng/ml的人数比例高于生存组(P<0.05);TNM分期为Ⅲ~Ⅳ期、淋巴结转移、PGⅠ/PGⅡ比值<1.68是影响胃癌患者预后的危险因素(P<0.05)。结论 胃癌患者血清PGⅠ/PGⅡ、TK1、CEA水平异常,各指标联合检测对患者生存情况具有预测价值,且TNM分期为Ⅲ~Ⅳ期、淋巴结转移、PGⅠ/PGⅡ比值<1.68可直接影响胃癌患者预后。

Value of serum pepsinogenⅠ andⅡ ratio for evaluating the malignant biological behaviors in gastric cancer lesions

Objective:To study the value of serum pepsinogenⅠ andⅡ ratio (PGR) for evaluating the malignant biological behaviors in gastric cancer lesions.Methods:The patients with gastric cancer who underwent radical surgery in 363 Hospital between July 2015 and February 2018 were selected as the gastric cancer group in the study, and the volunteers who had physical examination in 363 Hospital during the same period were selected as the control group. Serum was collected to measure pepsinogenⅠ and pepsinogenⅡ and then calculate the PGR;gastric cancer lesions were collected to measure the expression of oncogenes and angiogenesis genes.Results:Serum PGR level of the gastric cancer group was significantly lower than that of the control group, serum PGR level of the patients with moderately-highly differentiated gastric cancer was significantly higher than that of the patients with lowly differentiated gastric cancer, serum PGR level of the patients with TNM stage III gastric cancer was significantly lower than that of the patients with TNM stage I+II gastric cancer, and serum PGR level of the gastric cancer patients with lymph node metastasis was significantly lower than that of the gastric cancer patients without lymph node metastasis;PGR=3.8 was taken as the cutoff point, and p53 and TXNIP mRNA expression in the lesions of the gastric cancer patients with PGR < 3.8 were significantly lower than those of the gastric cancer patients with PGR > 3.8 while Bcl-2,β-catenin, Survivin, COX-2, HIF-1α, VEGF, c-Met and CNPY2 mRNA expression were significantly higher than those of the gastric cancer patients with PGR > 3.8.Conclusion:The decrease of PGR in serum of patients with gastric cancer is valuable for evaluating the pathological process and malignant biological behaviors.

Correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer

Objective: To investigate the correlation of serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation of cancer cells in patients with gastric cancer. Methods:Superficial gastritis group (n=247), gastric ulcer group (n=159) and gastric cancer group (n=97) who were pathologically diagnosed by gastroscopy in Chongqing wanzhou district people's hospital of 5 between August 2016 and August 2017 were selected, and the differences in serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content as well as proliferation and apoptosis gene expression in lesion tissue were compared among the three groups. Pearson test was used to evaluate the correlation of pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content with malignant proliferation activity of cancer cells in patients with gastric cancer. Results: Serum pepsinogenⅠ/Ⅱ ratio and gastrin-17 content in gastric cancer group were lower than those in gastric ulcer group and superficial gastritis group. Proliferation genes EIF5A2, MACF1 and PIK3CD mRNA expression levels in gastric cancer group were higher than those in gastric ulcer group and superficial gastritis group whereas SIRT1 mRNA expression level was lower than that in gastric ulcer group and superficial gastritis group;apoptosis gene Livin mRNA expression level was higher than that in gastric ulcer group and superficial gastritis group whereas Bad and Noxa mRNA expression levels were lower than those in gastric ulcer group and superficial gastritis group;serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content in gastric cancer group were negatively correlated with EIF5A2, MACF1, PIK3CD and Livin mRNA expression levels, and positively correlated with SIRT1, Bad and Noxa mRNA expression levels. Conclusion: The serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17 content abnormally reduce in patients with gastric cancer, and the specific levels are directly correlated with gastric cancer cell proliferation and apoptosis activity.

胃蛋白酶原Ⅰ、Ⅱ的酶免疫分析

本文建立了胃蛋白酶原Ⅰ、Ⅱ(PGⅠ、PGⅠ)的酶免疫分析(EIA)方法。将抗PGⅠ单抗PGA4或抗PGⅡ单抗PGC8包被在板条微孔内,制成固相抗体,用过碘酸钠方法将抗PGⅠ单抗PGA7或抗PGⅡ单抗PGC10与辣根过氧化物酶相联结,成为标记抗体,二者与不同量的PGⅠ、Ⅱ标准品在磷酸缓冲液中保温反应后,根据测量数据画出标准曲线。对于PGⅠ、PGⅡBmax/B0分别为72.0和61.5,非特异结合分别小于1.3%和小于1.6%,灵敏度均为0.5ng/mL,批内CV分别为5.5%和6.8%,批间CV分别为12.0%和13.5%,回收率分别为98.5%和97.9%。测定40例胃癌组及40名正常组血清PGⅠ和PGⅡ,结果显示,胃癌血清PGⅠ低于正常组(P<0.001),PGⅡ高于正常组(P<0.01),PGⅠ/PGⅡ比值低于正常组(P<0.001)。新建PGⅠ、ⅡEIA与现行PGⅠ、ⅡIRMA具有良好的相关性。

血清胃蛋白酶原Ⅰ、Ⅱ及其比值诊断效能评价

目的以血清胃蛋白酶原Ⅰ(PGⅠ)、Ⅱ(PGⅡ)及其PGⅠ/PGⅡ比值(PGR)作为筛查慢性萎缩性胃炎和胃癌前期病变指标,评价其诊断效能。方法收集经胃镜排除胃肿瘤的患者474例,进一步将受检者分为轻度非萎缩性胃炎组(对照组,n=164)、萎缩性胃炎组(n=162)和萎缩性胃炎伴肠上皮化生(简称肠化)组(n=148)。以乳胶增强免疫比浊法定量检测血清PGⅠ和PGⅡ,计算PGR,通过受试者工作特征曲线(ROC)评价PGⅠ、PGⅡ和PGR的诊断价值。结果萎缩性胃炎组和萎缩性胃炎伴肠化组PGⅠ、PGⅡ和PGR较对照组显著降低(P<0.01)。PGⅠ、PGⅡ和PGR诊断萎缩性胃炎,其ROC曲线下面积(AUCROC)分别为0.679、0.593和0.622,最佳临界值分别为71.8、9.1和8.12,灵敏度分别为66.1%、54.3%和77.2%,特异度分别为61.0%、61.6%和43.9%;诊断萎缩性胃炎伴肠化AUCROC分别为0.787、0.583和0.836,最佳临界值分别为59.4、9.8和6.76,灵敏度分别为64.9%、58.8%和81.8%,特异度分别为78.1%、55.5%和77.4%。PGⅠ和PGR平行联合,灵敏度为93.6%、特异度为60.4%;PGⅠ和PGR序列联合,灵敏度为53%、特异度为95%。结论 PGⅠ和PGR作为监测胃黏膜状态的指标,联合运用能提高诊断效率;当PGⅠ和PGR同时小于最佳临界值时可预测萎缩性胃炎伴肠化。

上海青浦地区2016—2017年高龄人群血清胃蛋白酶原Ⅰ、Ⅱ的筛选试验

目的探讨血清胃蛋白酶原Ⅰ(PG-Ⅰ)、Ⅱ(PG-Ⅱ)水平的一致性、可变性。方法血清PG-Ⅰ、PG-Ⅱ检测采用酶联免疫吸附法,其中PG-Ⅰ<41 ng/mL和(或)胃蛋白酶原Ⅰ/Ⅱ比值(PGR)<3.1的受试者行电子胃镜检查。结果 PG-Ⅰ<12 ng/mL的受试者中,PG-Ⅰ和PGR在2年间检测结果比较无显著差异(P>0.05);在PG-Ⅰ12~41 ng/mL的受试者中,PG-Ⅰ和PGR在2年间检测结果比较有显著差异(P<0.01)。结论 PG-Ⅰ和PGR检测结果对胃镜检查的选择具有指导意义。

胃癌患者血清中胃蛋白酶原Ⅰ/Ⅱ比值和胃泌素-17含量与癌细胞恶性增殖的相关性

目的:探讨胃癌患者血清中胃蛋白酶原Ⅰ/Ⅱ比值和胃泌素-17含量与癌细胞恶性增殖的相关性。方法:选择2016.8~2017.8月期间收集胃镜活检病理确诊的浅表性胃炎组247例、胃溃疡组159例、胃癌组94例,对比三者血清胃蛋白酶原Ⅰ/Ⅱ比值和胃泌素-17含量,病灶组织中增殖及凋亡基因表达量的差异。采用Pearson检验评估胃癌患者胃蛋白酶原Ⅰ/Ⅱ比值和胃泌素-17含量与癌细胞恶性增殖活性的相关关系。结果:胃癌组血清胃蛋白酶原Ⅰ/Ⅱ比值、胃泌素-17含量低于胃溃疡组、浅表性胃炎组。胃癌组增殖基因EIF5A2、MACF1、PIK3CD mRNA表达量高于胃溃疡组、浅表性胃炎组,SIRT1mRNA表达量低于胃溃疡组、浅表性胃炎组;凋亡基因Livin mRNA的表达量高于胃溃疡组、浅表性胃炎组,Bad、Noxa mRNA的表达量低于胃溃疡组、浅表性胃炎组;胃癌组血清中胃蛋白酶原Ⅰ/Ⅱ比值、胃泌素-17含量与EIF5A2、MACF1、PIK3CD、Livin mRNA表达量呈负相关,与SIRT1、Bad、Noxa mRNA表达量呈正相关。结论:胃癌患者血清中胃蛋白酶原Ⅰ/Ⅱ比值和胃泌素-17含量异常降低,且具体水平与胃癌细胞增殖、凋亡活性直接相关。

血清胃蛋白酶原Ⅰ、Ⅱ比值对胃癌病灶内恶性生物学行为的评价价值研究

目的:研究血清胃蛋白酶原Ⅰ、Ⅱ比值(PGR)对胃癌病灶内恶性生物学行为的评价价值。方法:选择本院进行根治性手术的胃癌患者作为研究的胃癌组,同期在三六三医院体检的志愿者作为对照组。采集血清,测定胃蛋白酶原Ⅰ、胃蛋白酶原Ⅱ后计算PGR;采集胃癌病灶并测定癌基因、血管新生基因的表达量。结果:胃癌组患者血清PGR水平明显低于对照组且中高分化胃癌患者的血清PGR水平明显高于低分化胃癌患者,TNMⅢ期胃癌患者的血清PGR水平明显低于TNM I+Ⅱ期胃癌患者,有淋巴结转移胃癌患者的血清PGR水平明显低于无淋巴结转移的胃癌患者;以PGR=3.8为切点,PGR<3.8胃癌患者的胃癌病灶内p53、TXNIP的mRNA表达量明显低于PGR>3.8的胃癌患者,Bcl-2、β-catenin、Survivin、COX-2、HIF-1α、VEGF、c-Met、CNPY2的mRNA表达量明显高于PGR>3.8的胃癌患者。结论:胃癌患者血清中PGR的降低对病理进程及恶性生物学行为具有评估价值。

PGⅠ、PGⅡ在胃癌组织中的表达及意义

目的:研究胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)在胃癌组织中的表达及意义。方法:将我院2011年5月至2013年10月收治的上消化道疾病患者243例纳入研究,根据胃镜及病理组织学结果,按照胃癌、慢性萎缩性胃炎、慢性非萎缩性胃炎、不典型增生以及胃溃疡分为5组,对照组为57名来我院检查的健康的人群。应用酶联免疫法测定各组血清PGⅠ、PGⅡ的含量并计算胃蛋白酶原比值(PGR),比较胃癌患者手术前后血清PGⅠ、PGⅡ的含量以及PGR,并通过ROC曲线下面积评价血清PGⅠ、PGⅡ以及PGR诊断胃癌的效能。结果:与对照组比较,胃溃疡组PG Ⅰ、PG ⅠⅠ均明显升高,PGR降低(P<0.05),慢性萎缩性胃炎组、不典型增生组及胃癌组PGⅠ、PGR均明显降低(P<0.05);与慢性萎缩性胃炎组比较,不典型增生组和胃癌组PGR显著降低(P<0.05)。手术治疗后,胃癌患者血清PGⅠ、PGⅡ含量较手术前明显下降(P<0.05)。血清PGⅠ、PGⅡ以及PGR含量诊断胃癌的ROC曲线下面积依次为0.779、0.920以及0.991。结论:胃癌患者血清PGⅠ、PGR均明显降低,二者可用于初步筛查胃癌。

血清胃蛋白酶原检测与胃镜检查对慢性萎缩性胃炎临床诊断价值的比较

目的比较血清胃蛋白酶原(PG)Ⅰ、PGⅡ水平及PGⅠ/PGⅡ比值(PGR)与胃镜检查对慢性萎缩性胃炎(CAG)的临床诊断价值。方法以病理诊断为金标准,将205例患者分为CAG组(103例)和慢性非萎缩性胃炎组(对照组,102例)。所有患者均进行血清PG检测及胃镜检查,计算PG和胃镜诊断CAG的敏感性、特异性、阳性预测值、阴性预测值。结果 CAG组血清PGⅠ[(74.43±39.62)μg/L]、PGR(2.70±1.05)明显低于对照组[PGⅠ为(94.89±36.30)μg/L、PGR为3.55±0.90,P<0.01],而PGⅡ2个组之间差异无统计学意义(P>0.05)。血清PGⅠ、PGR、胃镜诊断CAG的敏感性分别为66.0%、67.0%、74.8%,特异性分别为62.7%、77.5%、80.4%,阳性预测值分别为64.2%、75.0%、79.4%,阴性预测值分别为64.6%、70.0%、75.9%;PGR诊断CAG的敏感性、特异性、阳性预测值、阴性预测值与胃镜检查比较,差异均无统计学意义(P>0.05),PGⅠ诊断CAG的特异性和阳性预测值明显低于PGR及胃镜检查(P<0.05)。结论血清PGR与胃镜检查对CAG的临床诊断价值相当。在大量筛查CAG时或对于不适用胃镜检查的患者,PG检测有望替代胃镜检查用于对CAG的临床辅助诊断。

血清胃蛋白酶原、胃泌素17联合检测在健康体检中的应用价值

目的探讨血清胃蛋白酶原(PG)Ⅰ、PGⅡ、PGⅠ/PGⅡ比值(PGR)、胃泌素17(G-17)在健康体检中的价值。方法采用酶联免疫吸附试验(ELISA)检测1 872名表观健康者血清PGⅠ、PGⅡ、G-17水平,并计算PGR。分析性别、年龄与血清PGⅠ、PGⅡ、PGR、G-17的关系,以PG和G-17同时阳性作为筛查方案,比较其与胃镜检查结果的符合率。结果表观健康人群男、女性之间血清PGⅠ水平、PGR差异均有统计学意义(P<0.001),而PGⅡ、G-17水平差异无统计学意义(P>0.05)。随着年龄的增长,PGⅠ和PGⅡ水平逐渐上升,而PGR则呈下降趋势。血清G-17在21~50岁时为平台期,50岁之后G-17水平逐渐上升。男、女性之间血清PG、G-17阳性率以及PG与G-17同时阳性的比例差异均无统计学意义(P>0.05)。G-17阳性率明显高于PG阳性率(P<0.001)。PG和G-17同时阳性的筛查方案与胃镜检查结果的阳性符合率为12.5%。结论血清PG、G-17联合检测对胃相关疾病的筛查具有重要意义,适合在体检人群中推广。

健康体检人群中胃蛋白酶原对慢性萎缩性胃炎的诊断价值

目的探讨上海地区健康体检人员中血清胃蛋白酶原(PG)对慢性萎缩性胃炎(CAG)的诊断价值。方法选择2020年1月至2021年1月来本院体检的上海地区健康体检人员,将其中280例经胃镜病理诊断为CAG的体检人员纳入病例组;选择同期280例非CAG健康体检人员纳入对照组。两组均进行血清PG测定,分析两组PGⅠ、PGⅡ、PGⅠ/PGⅡ水平以及上述指标诊断CAG的敏感性、特异性、阳性预测值和阴性预测值。结果病例组PGⅠ[(77.35±21.52)vs(97.51±23.31)ng/ml]、PGⅠ/PGⅡ[(3.31±0.68)vs(4.21±1.02)]水平与对照组比较差异均有统计学意义(均P<0.05),两组PGⅡ水平比较差异无统计学意义(P>0.05)。PGⅠ诊断CAG的敏感性为54.08%,特异性为80.95%,阳性预测值为85.71%,阴性预测值为10.56%,AUC值为0.734;PGⅡ诊断CAG的敏感性为52.63%,特异性为64.55%,阳性预测值为75.40%,阴性预测值为34.42%,AUC值为0.532;PGⅠ/PGⅡ诊断CAG的敏感性为75.68%,特异性为68.42%,阳性预测值为84.66%,阴性预测值为57.26%,AUC值为0.706。结论PGⅠ和PGⅠ/PGⅡ对筛选健康体检人群CAG具有较高价值,值得推广。