老年胃癌患者相关细胞因子动态变化与临床预后的关系

目的通过对老年胃癌患者手术前、后动态检测血清中白细胞介素-6（IL-6）、血管内皮生长因子-A（VEGF-A）表达,探讨IL-6、VEGF-A动态变化与老年胃癌患者预后的相关性。方法老年胃癌组为67例老年胃癌患者;对照组为69例消化道良性疾病患者。分别在手术前、后采血,用双抗体夹心法（ELISA）动态检测两组患者血清IL-6、VEGF-A的表达。结果①术前老年胃癌组、对照组血清IL-6、VEGF-A表达水平有明显差异（P〈0.01）;②老年胃癌组手术前后血清IL-6、VEGF-A水平表达呈明显差异（P〈0.01）。③老年胃癌组手术后与对照组血清IL-6表达无明显差异（P〉0.05）;VEGF-A表达仍高（P〈0.05）。结论根据两组患者术前后IL-6、VEGF-A表达的动态变化,显示血清IL-6、VEGF-A表达与老年胃癌患者预后呈正相关性。     

非小细胞肺癌患者血清血管内皮生长因子、血小板衍生生长因子和表皮生长因子受体测定的临床意义

目的 探讨血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、血小板衍生生长因子(platelet-derived growth factor,PDGF)和表皮生长因子受体(epidermal growth factor receptor,EGFR)测定在非小细胞肺癌(non-small cell lung cancer,NSCLC)诊断和预后判定中的意义.方法 采用双抗体夹心ABC-ELISA法测定31例NSCLC患者及30名健康者血清VEGF、PDGF和EGFR的含量.结果 NSCLC患者血清VEGF、PDGF和EGFR测定值均高于健康对照组(P值均＜0.01).血清VEGF、PDGF和EGFR测定值与NSCLC病理分型无关(P值均＞0.05),与远处转移有关,远处转移组的测定值高于未转移组(P＜0.05～0.01).NSCLC患者血清VEGF与PDGF测定值之间呈显著正相关(r=0.641,P＜0.01),血清VEGF和EGFR测定值呈正相关(r=0.369,P＜0.05).结论 检测血清VEGF、PDGF和EGFR水平对NSCLC的诊断和预后判定具有一定价值.     

急性白血病患者血清VEGF及VEGFR-2的临床研究

目的：探讨急性白血病（AL）患者血清中血管内皮生长因子（VEGF）及其受体2（VEGFR-2）的表达水平与临床的关系,以及血管新生在AL发病中的作用。方法：采用双抗体夹心ELISA法检测20例健康志愿者与39例AL初发患者未治时血清VEGF及VEGFR-2的含量,及25例获得完全缓解后的AL患者血清VEGF及VEGFR-2的水平;同时留取39例AL初发患者骨髓液涂片,进行瑞特染色后检测骨髓原始和幼稚细胞水平。结果：血清VEGF、VEGFR-2在AL初发组的含量明显高于正常对照组,尤其在未缓解组,P〈0.05;急性非淋巴细胞白血病（ANLL）和急性淋巴细胞白血病（ALL）之间血清VEGF、VEGFR2的水平差异无统计学意义（P〉0.05）;25例完全缓解的AL患者,其缓解前、后的血清VEGF、VEGFR2水平均高于正常对照组,差异有统计学意义（P〈0.05）,同时缓解后较缓解前血清VEGF、VEGFR2水平也明显下降（P〈0.05）;血清VEGF、VEGFR2的含量与患者骨髓中原始幼稚细胞水平有一定的相关性（均P〈0.05）。结论：提示AL患者有血管新生的存在,且血清VEGF及VEGFR-2水平与病情的特征以及预后的判断有一定的相关性。     

胃癌患者手术前后血清IGF-Ⅰ、IGF-ⅠR、IGF-Ⅱ水平变化及意义

目的观察胃癌患者手术前后血清胰岛素样生长因子Ⅰ(IGF-Ⅰ)、IGF-Ⅰ受体(IGF-ⅠR)、胰岛素样生长因子Ⅱ(IGF-Ⅱ)水平变化,并探讨其临床意义。方法选择行胃癌根治术的胃癌患者50例(观察组)、体检健康者50例(对照组),检测观察组手术前后、对照组体检日血清IGF-Ⅰ、IGF-ⅠR、IGF-Ⅱ。分析各指标与胃癌患者临床病理特征的关系。结果观察组术前血清IGF-Ⅰ、IGF-ⅠR、IGF-Ⅱ水平均高于术后及对照组(P均<0.05),但术后各指标与对照组比较差异均无统计学意义(P均>0.05)。单因素分析显示,低分化者血清IGF-Ⅰ、IGF-ⅠR、IGF-Ⅱ水平明显高于高分化、中分化者,TNM分期Ⅲ、Ⅳ期者明显高于Ⅰ、Ⅱ期者,有淋巴结转移者明显高于无淋巴结转移者(P均<0.05)。结论胃癌患者术前血清IGF-Ⅰ、IGF-ⅠR、IGF-Ⅱ水平明显升高,其水平变化与肿瘤的组织分化程度、淋巴结转移、TNM分期有关。     

非小细胞肺癌组织中EGFR、VEGFR-3、PDGFR的表达及临床病理学评价

目的探讨表皮生长因子受体（EGFR）、血管内皮生长因子受体-3（VEGFR-3）和血小板源性生长因子受体（PDGFR）的表达与非小细胞肺癌（NSCLC）生物学行为的关系及其内在联系。方法用免疫组化SP法对205例Ⅰ-Ⅲ期NSCLC根治手术后的标本进行EGFR、VEGFR-3、PDGFR表达检测。结果 EGFR、VEGFR-3、PDGFR的阳性表达率分别为36.1%、90.2%、61.5%。EGFR的表达与淋巴结转移个数有关;VEGFR-3表达与N分期、胸膜侵犯有关。PDGFR的表达评分与VEGFR-3的表达评分呈正相关,r=0.255,P=0.001。结论 EGFR、VEGFR-3是NSCLC淋巴转移与局部侵犯的相关因素,PDGFR与VEGFR-3可能存在某种内在联系,对多靶点靶向药物的研发及靶向治疗药物的联合应用具有提示意义。     

NSCLC患者血清miR-181a的表达变化及其与铂类药物化疗敏感性的关系

目的观察微小RNA（miR）-181a在早期非小细胞肺癌（NSCLC）患者血清中的表达变化,并分析其与铂类药物化疗效果的相关性。方法采用茎环结构的逆转录实时定量PCR方法,检测40例早期NSCLC患者（NSCLC组）术前及其中30例铂类药物化疗前后血清miR-181a水平,同时设40例健康体检者为对照组;分析血清miR-181a水平与NSCLC临床病理特征及铂类药物化疗效果的关系。结果NSCLC组术前和对照组血清miR-181a表达量分别为0．00259、0．00729（P〈0．0001）,前者与肿瘤临床病理特征问无统计学相关性（P均〉0．05）;NSCLC组30例患者化疗前后血清miR-181a相对表达量分别为0．00279、0．00625（P=0．0001）,其中化疗无效、有效者分别为0．00456、0．00793,化疗无效者显著低于化疗有效者及对照组（P分别为0．015、0．005）,后两者比较无显著差异（P=0．806）。结论miR-181a在早期NSCLC患者血清中的水平降低,并与铂类药物化疗敏感性相关;可能作为潜在的生物标记物用于NSCLC的早期诊断及化疗敏感性预测。     

非小细胞肺癌患者EGFR、ALK基因突变及临床病理特征与预后的相关性研究

目的探讨非小细胞肺癌(NSCLC)患者EGFR、ALK基因突变状态及病理特征,分析二者与患者预后情况相关性。方法收集2015年1月至2018年1月苏州大学附属第一医院病理确诊的NSCLC病例262例,记录患者临床病理特征及转归,采用突变增阻滞系统(ARMS)-Taqman探针法及RT-PCR检测患者肿瘤样本的EGFR和ALK基因外显子突变情况,采用Kaplan-Meier法和Cox风险回归考察不同基因突变情况的预后、临床病理特征与临床结局的相关性。结果262例NSCLC患者中,168例为野生型,ALK突变12例,突变率4.6%;EGFR突变82例,突变率31.30%,其中18号外显子突变2例,19号外显子突变37例,20号外显子突变9例,21号外显子突变31例;各组间年龄、病理类型比较差异有统计学意义,P<0.05;Wild type组中位OS时间11.6月,ALK组中位OS时间15.0月,EGFR组中位OS时间36.8月,EGFR组OS明显优于ALK组OS时间及Wild type组OS时间,P<0.05;EGFR19号外显子突变组、21号外显子突变组OS生存时间显著高于18号外显子突变组和20号外显子突变组,P<0.05;EGFR阴性(RR=15.751,95%CI:9.252~26.816)、鳞癌(RR=18.344,95%CI:6.187~54.388)为OS的危险因素。结论EGFR突变状态、病理类型对非小细胞肺癌预后具有良好的预测价值,鳞癌和EGFR阴性患者生存期短。EGFR基因少见突变(18号外显子、20号外显子)患者的中位OS时间更短。     

胃癌患者VEGF和Endostatin的表达及其与临床病理特征的关系

目的探讨胃癌患者手术前后血清血管内皮生长因子（VEGF）和Endostatin的动态变化规律及其与临床病理特征的关系。方法采用ELISA法检测胃癌患者（胃癌组）术前及术后2周血清VEGF和Endostatin水平,并与慢性胃炎患者（胃炎组）和健康对照者（对照组）进行比较。结果①胃癌组术前血清VEGF、Endostatin水平均显著高于胃炎组及对照组（P均〈0．01）。②胃癌组术前血清VEGF、Endostatin水平与细胞分化程度、肿瘤大小、浸润深度、淋巴结转移、远处转移及临床分期密切相关（P均〈0．05）,与性别、肿瘤部位等因素无关（P〉0．05）。③胃癌组术后2周血清VEGF水平较术前显著下降,而血清Endostatin水平较术前升高（P均〈0．01）。结论血清VEGF和Endostatin水平是评价胃癌恶性行为、预测浸润和转移程度的有效指标。     

恶性胸腔积液中EGFR突变和肿瘤标志物的关系探讨

目的 探讨非小细胞肺癌(NSCLC)伴恶性胸腔积液患者胸腔积液中表皮生长因子受体(EGFR)突变和肿瘤标志物的关系.方法 收集2013年1月至2016年8月于重庆医科大学附属第一医院经病理证实的晚期NSCLC患者49例.分别对患者的胸腔积液进行肿瘤标志物和EGFR基因检测,同时应用SPSS 23.0软件分析临床特征、肿瘤标志物表达水平和EGFR突变的关系.结果 在49例NSCLC患者中,EGFR突变率为55.1％,EGFR突变和各临床特征间的关系无统计学意义.同时在EGFR突变和肿瘤标志物的关系方面,EGFR突变率随着癌胚抗原和乳酸脱氢酶的表达水平的升高而升高.结论 恶性胸腔积液中肿瘤标志物水平的高低和EGFR突变状态在一定程度上有关.对于不易获取肿瘤组织标本的恶性胸腔积液患者来说,胸腔积液中肿瘤标志物水平可以指导EGFR-酪氨酸激酶抑制剂的使用.     

胃癌患者血清胃肠激素、血管内皮生长因子及相关指标的变化

目的探讨分析胃癌患者血清胃肠激素、血管内皮生长因子(VEGF)及相关指标的变化。方法 60例胃癌患者为观察组,并以同时期进行体检的60名健康人员为对照组,将两组血清胃肠激素、VEGF及相关指标水平进行检测与比较,然后将其中不同疾病分期及病灶部位者的检测水平进行比较。结果观察组血清胃肠激素、VEGF-A、VEGF-C、VEGF-D及VEGFR-1、VEGFR-2、sVEGFR-1均高于对照组,而血清sVEGFR-1则低于对照组,不同疾病分期者的上述指标检测水平也存在明显差异(P均<0.05),但不同病灶部位者的检测水平之间无显著性差异(P均>0.05)。结论胃癌患者的血清胃肠激素、VEGF及相关指标呈现异常的状态,且不同分期者之间也有明显的差异。     

Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma

AIM： TO analyze the serum levels and prognostic significance of vascular endothelial growth factor （VEGF） -A, -C, and -D, and their receptors, VEGFR-1 and -2 in gastric adenocarcinomas. METHODS： The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay （ELISA）. These measurements were correlated with clinco-pathological features and survival rates. RESULTS： The serum levels of VEGF-A and its receptor, VEGFR-1, were significantly higher in patients with gastric cancer than in healthy donors （t = 2.3, P = 0.02 and t = 4.2, P 〈 0.0001, respectively）. In contrast, the serum levels of VEGF-D were significantly higher in control subjects than in patients （t = 2.9, P = 0.004）. There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis, advanced overall stage,tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION： Serum VEGF levels vary significantly in the same cohort of patients with variable clinicopathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.     

Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer

BackgroundA hormonal role in the development of non-small cell lung cancer (NSCLC) has been well documented, and the classic estrogen receptors (ERs)—ERα and ERβ have been extensively investigated over the past decade. The expression of ERβ was found to be high and display biological activity in NSCLC, but anti-estrogen therapy targeting this receptor has shown limited efficacy for the disease. The third estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30), was recently found to be highly expressed in NSCLC. Herein, we aimed to investigate the expression profile of GPER1 and correlate it with clinicopathological factors as well as postoperative prognosis in NSCLC.MethodsWe examined GPER1 and ERβ expression using immunohistochemistry among 183 NSCLC cases, including 132 lung adenocarcinoma (LUAD) with identified epidermal growth factor receptor (EGFR) mutation status and 51 squamous cell carcinoma (SCC) patients. We then conducted correlation analysis between the expression of GPER1 and clinicopathological factors and patients’ postoperative prognosis.ResultsPositive expression of GPER1 was categorized into 2 main classes: nuclei-GPER1 (nGPER1) and concurrent nuclei-and cytoplasm-GPER1 (n/cGPER1), according to its subcellular localization. The LUAD with wild-type EGFR (wt-EGFR) had a higher frequency of n/cGPER1 (50%) but a lower frequency of nGPER1 (31%) when compared with those with mutated EGFR (n/cGPER1: 31%, nGPER1: 41%, respectively). The expression of GPER1, regardless of subcellular localization, was positively correlated with tumor stage and lymph node metastasis. The median recurrence-free survival (mRFS) and overall survival (OS) were significantly worse in participants with n/cGPER1 expression than in those with nGPER1 or without GPER1 expression.ConclusionsThis study revealed that GPER1 is aberrantly highly expressed and presents a unique GPER1 expression profile in NSCLC. The n/cGPER1 expression was significantly associated with EGFR mutation status, tumor stage, lymph node metastasis, and poor postoperative prognosis in NSCLC.     

Clinicopathological features and epidermal growth factor receptor mutations associated with epithelial–mesenchymal transition in non-small cell lung cancer

Background and objective:   Small molecular inhibitors of the epidermal growth factor receptor (EGFR) have been extensively studied in non-small cell lung cancer (NSCLC) patients. The discovery of molecular biomarkers that identify the subgroups of NSCLC patients benefiting from EGFR tyrosine kinase inhibitor (TKI) has become an important area of investigation. Recent studies have suggested that epithelial–mesenchymal transition (EMT) in tumours decreases the cellular requirements for EGFR signalling pathway, and this may provide a molecular signature to define those NSCLC patients most likely to respond to treatment with targeted EGFR TKI. This research explored the clinicopathological features and EGFR mutations associated with EMT in NSCLC.
Methods:   The EMT status in surgically resected specimens from 62 patients with NSCLC was tested by immunohistochemical staining. The frequency of tumour epithelial phenotype was calculated and the strength of the association with clinicopathological features and EGFR genotype was determined by logistic regression.
Results:   The overall frequency of the epithelial phenotype was 35.48% (22 of 62). Based on univariate analyses, the frequency of the epithelial phenotype (E-cadherin-positive) was greater for EGFR mutants versus wild types (77.78% vs 18.18%; P  < 0.0001) and women versus men (54.55% vs 25%; P  = 0.02). Multivariate logistic analysis showed that only the EGFR genotype (odds ratio, 0.063; 95% CI: 0.013–0.3; P  = 0.0005) was significantly associated with the epithelial phenotype.
Conclusion:   In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.     

非小细胞肺癌患者血清血管内皮生长因子水平的变化及与临床的关系

目的研究非小细胞肺癌患者血清血管内皮生长因子(VEGF)水平的变化及与临床分期和病理类型的关系。方法三组研究对象为非小细胞肺癌组患者96例,支气管、肺良性病变组40例,健康对照组30例,采用ELISA法进行血清VEGF的检测。结果非小细胞肺癌组的血清VEGF水平显著高于其它两组(P<0.01);非小细胞肺癌患者血清VEGF水平随临床分期的递增而逐步升高,各期间比较差异有显著性(P<0.05);不同病理类型非小细胞肺癌患者血清的VEGF水平之间无显著性差异(P>0.05)。结论非小细胞肺癌患者的血清VEGF水平升高和随临床分期递增而明显升高的改变对非小细胞肺癌的临床分期和预后产生了重要影响,而这种改变并不受病理类型的影响,有助于我们对非小细胞肺癌患者的治疗效果和预后进行判断。     

人类乳头瘤病毒与广东地区非小细胞肺癌相关性研究

目的：通过前瞻性观察广东地区非小细胞肺癌(non-small cell lung cancer,NSCLC)患者中人乳头瘤病毒(human papillomavirus,HPV)的阳性率,以及 HPV 阳性与否与血管内皮生长因子(vascular endothelial growth factor,VEGF)和表皮生长因子受体(epidermal growth factor receptor,EGFR)表达水平的关系,探讨 HPV与广东地区 NSCLC 的相关性。方法采用 PCR 方法检测44例 NSCLC患者(分成吸烟组与非吸烟组)和24例肺良性病变患者肺组织中 HPV 的 DNA。采用酶联免疫吸附试验法检测 NSCLC 患者中 HPV DNA 阳性组和 HPV DNA 阴性组血清 VEGF、EGFR的水平。结果 NSCLC 组 HPV DNA 阳性率(18/44,40.91%)明显高于肺良性病变组(3/24,12.50%)(χ2=5.8718,P<0.05)。NSCLC患者中 HPV阳性组 VEGF和 EGFR 的水平均明显高于 HPV阴性组[VEGF：(509.19±216.14)ng/L vs (80.80±61.06)ng/L,T=627.00,P<0.01;EGFR：(2482.41±92.47)ng/L vs (2254.59±74.85)ng/L,T=639.00,P <0.01]。NSCLC 中吸烟者27例,HPV阳性率为40.74%(11/27);非吸烟者17例,HPV 阳性率为41.18%(7/17),2组比较差异无统计学意义(χ2=0.005,P>0.05)。结论 HPV可能是广东地区 NSCLC 发生的潜在因素,预防 HPV感染对降低肺癌的发生有一定的意义。     

萎缩性胃炎患者幽门螺杆菌根除后表皮生长因子及其受体的变化

目的　研究幽门螺杆菌 (Helicobacterpylori,H .pylori)感染对胃黏膜表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)、血清表皮生长因子 (epidermalgrowthfactor,EGF)水平的影响。方法　对 60例H pylori检测阳性的慢性萎缩性胃炎患者进行根除治疗 ,在治疗前及疗程结束 3个月后分别进行胃镜检查 ,并采用免疫组化及放射免疫法测定H pylori根除前后胃黏膜EGFR和血清EGF含量。 3 0例H pylori检测阴性且胃镜检查无明显异常者作为正常对照组。结果　 60例H pylori检测阳性的CAG患者的胃黏膜EGFR阳性率及血清EGF水平均高于正常对照 ,其差异有显著性 (P <0 0 5 ,P <0 0 1)。有 3 1例在根除治疗 3个月后进行了复查 ,其中 2 4例H pylori得到成功根除。 2 4例H pylori得到根除的CAG患者 ,根除后血清EGF水平明显下降 (P <0 0 1) ,而EGFR阳性率无改变 (P >0 0 5 )。结论　H pylori感染引起胃黏膜EGFR阳性率及血清EGF水平增加 ,根除H pylori后血清EGF可恢复至正常水平 ,而胃黏膜EGFR阳性率在短期内没有明显改变     

Identification of EGFR and KRAS mutations in Chinese patients with esophageal squamous cell carcinoma

The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)‐targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin‐fixed paraffin‐embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18–21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation (n= 1), in‐frame deletion (n= 2), and L858R missense mutation (n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed.