MMP13在非小细胞肺癌组织中的表达及其预后价值

目的 探讨MMP13在非小细胞肺癌（NSCLC）组织中的表达及其与浸润、转移和预后的关系。方法 采用免疫组化法检测87例NSCLC组织和30例癌旁正常组织中MMP13蛋白的表达水平。分析MMP13表达与NSCLC临床病理特征的关系,应用Kaplan-Meier法和多因素Cox模型对87例NSCLC患者的生存进行分析。结果MMP13在NSCLC组织和癌旁正常组织中的阳性表达率分别为70.1％（61／87）和6.7％（2／30）,差异具有统计学意义（P＜0.001）。MMP13表达与T分期、淋巴结转移和TNM分期有关（P＜0.05）。Kaplan-Meier法生存分析曲线显示,MMP13阳性表达组患者的5年生存率为18。4％,显著低于阴性表达组的52。1％（P=0.001）,同时TNM分期（P＜0.001）、淋巴结转移（P＜0.001）和T分期（P=0.002）均可影响生存期。Cox模型多因素分析显示,仅MMP13表达（P=0.042）和TNM分期（P=0.001）是影响肺癌预后的独立因素。结论 MMP13与肺癌的浸润和转移密切相关,可能是肺癌预后判断的一项指标。     

MT1-MMP和MMP11在肺癌中的表达及其预后价值

目的探讨MT1-MMP和MMP11在肺癌组织中的表达及其与浸润转移和预后的关系。方法采用免疫组化检测47例肺鳞癌和42例肺腺癌组织中MT1-MMP和MMP11蛋白的表达。结果 MT1-MMP蛋白阳性表达率在肺鳞癌和腺癌组织中分别为68.1%(32/47)和64.3%(27/42)(P=0.705),其表达与T分期、淋巴结转移和TNM分期相关(P<0.05)。MMP11蛋白在肺鳞癌和腺癌组织中的阳性表达率分别为61.7%(29/47)和57.1%(24/42)(P=0.662),其表达与淋巴结转移和TNM分期相关(P<0.05)。MT1-MMP和MMP11表达呈正相关(γ=0.332,P=0.001)。Kaplan-Meier生存曲线显示MT1-MMP和MMP11阳性表达组5年生存率均显著低于阴性表达组(P<0.05)。结论MT1-MMP和MMP11的表达与肺癌的浸润转移密切相关,两者的阳性表达均提示肺癌患者的不良预后。     

基质金属蛋白酶-10在肺腺癌和肺鳞癌中的差异性表达

0引言基质金属蛋白酶(matrix metalloproteinases,MMPs)是人体内降解基底膜和细胞外基质(extra-cellar matrix,ECM)的主要酶类,参与肿瘤演进等众多生理和病理过程。基质金属蛋白酶-10(MMP-10,stromelysin-2)是基质金属蛋白酶中的一个成员,本研究采用免疫组织化学SP法检测MMP-10在肺癌组织中的表达情况,并分析其与肺癌临床病理及预后的关系。     

基质金属蛋白酶MMP2表达与乳腺癌转移及预后的关系

目的：探讨乳腺癌MMP2蛋白表达的临床意义。方法：应用免疫组织化学方法对乳腺癌石蜡标本进行检测，并与患者临床病理指标进行分析。结果：乳腺癌MMP2蛋白阳性反应率为45．8％，与肿瘤大小，腋淋巴结转移相关（P＜0．05），MMP2阴性者生存期延长（P＜0．05），结论：MMP2参与了乳腺癌的发生，发展过程，可能是患者预后的不良指标。此结果为临床建立新的乳腺癌预后预测因子提供有价值的信息。     

肺腺癌和鳞癌中VEGF-C和新生淋巴管表达的预后价值

背景与目的血管内皮生长因子-C(vascu larendothelial growth factor-C,VEGF-C)是VEGF家族的成员之一,且已被证明是相对特异的血管内皮生成因子,其与受体VEGFR-3结合后可激活淋巴管的生成,为肿瘤的淋巴结转移创造有利的条件。本研究旨在探讨VEGF-C和新生淋巴管在肺腺癌和鳞癌中的表达特点及其预后意义。方法以跨粘膜样受体蛋白(podoplanin)标记新生淋巴管内皮细胞,采用免疫组化方法检测98例IIIa(N2)期肺腺癌和鳞癌中VEGF-C和新生淋巴管的表达。结果 VEGF-C的表达率与微淋巴管密度(lymphatic microvessel density,LMVD)之间存在正相关(r=0.783,P<0.01)。VEGF-C高表达组的LMVD大于低表达组(P<0.01)。肺腺癌VEGF-C和新生淋巴管表达率明显高于肺鳞癌(P<0.01)。VEGF-C阳性表达患者的生存率明显低于阴性患者(P<0.05),VEGF-C是影响预后的独立因素。结论 IIIa(N2)期肺腺癌新生淋巴管的表达较鳞癌明显。VEGF-C是影响IIIa(N2)期肺腺癌和鳞癌患者预后的独立因素。     

CDHR2在肺腺癌中的表达及其与预后的关系

目的探讨CDHR2在肺腺癌(LUAD)组织中的表达及其与临床病理特征和预后的关系,并分析CDHR2与LUAD肿瘤免疫浸润的关系。方法挖掘TCGA、GEPIA数据库中CDHR2在LUAD中的表达及与预后的关系;免疫组织化学染色检测83例LUAD患者的癌组织及癌旁正常组织中CDHR2的表达情况,并分析其与患者临床病理特征及无病生存期(DFS)的关系。通过TIMER和CIBERSORT数据库分析CDHR2与LUAD肿瘤免疫浸润水平之间的关系。结果 TCGA数据集中515例LUAD组织的CDHR2表达水平显著高于59例癌旁正常组织(P<0.05)。GEPIA数据库发现CDHR2高表达与较差的总生存期(OS)有关(P<0.05)。免疫组化显示CDHR2蛋白在LUAD组织中的高表达率为66.3%(55/83),高于癌旁组织的37.3%(31/83),差异有统计学意义(P<0.05)。CDHR2蛋白表达与TNM分期有关(P<0.05)。CDHR2蛋白高表达患者的中位DFS为44.6(95%CI:39.5～49.7)个月,短于低表达患者的57.3(95%CI:49.9～64.8...     

OPN在胆管腺癌组织中的表达及其与预后的关系

目的:检测OPN在胆管腺癌、癌旁胆管组织中的表达,了解OPN在胆管腺癌组织中的表达及其与预后的关系.方法:采用免疫组化SP法检测OPN在44例胆管腺癌、44例癌旁胆管组织中的表达情况,分析OPN与胆管癌临床病理参数的关系,并对患者进行随访.结果:OPN在胆管腺癌、癌旁胆管组织中表达阳性率分别为68.2%(30/44)、27.3%(12/44),在胆管腺癌组织中表达阳性率明显高于癌旁胆管组织(P<0.05).OPN在胆管腺癌组织中的表达与胆管癌浸润深度、淋巴结转移相关(P<0.05),差异有统计学意义.OPN阳性表达患者术后5年总体生存率明显低于阴性患者(P=0.015).结论:OPN在胆管腺癌组织中高表达,与胆管癌的侵袭、转移及预后密切相关,可作为胆管腺癌的参考指标,对胆管腺癌的诊断和预后评估具有重要意义.     

PKCζ在肺腺癌中的表达与侵袭转移及预后关系的探讨

目的:研究PKC ζ 在肺腺癌组织中的表达与肿瘤侵袭、转移和预后的关系,初步分析PKC ζ 促进肿瘤转移的分子机制。方法:采用特异的PKC 抑制剂抑制PKC ζ 的活性,观察PKC ζ 活性下降对肺腺癌A549 细胞趋化运动和粘附能力的影响。选择临床及随访资料完整的48例肺腺癌患者,采用免疫组织化学法检测肺腺癌组织中PKC ζ 的表达情况,结合临床病理参数分析PKC ζ 表达与临床预后的关系。结果:PKC 家族中的非典型PKC 参与了肺癌细胞的趋化和黏附过程,通过抑制PKC ζ 的活性明显减弱了EGF 诱导的A549 细胞的趋化运动和对细胞外基质的黏附能力。25例（52%）患者肺腺癌组织中癌细胞PKC ζ 呈阳性表达且表达定位在胞浆;PKC ζ 蛋白表达与患者出现淋巴结转移有关（P<0.05）,与性别、年龄、肿瘤大小、吸烟与否、远处转移和临床分期等其它临床病理参数无关;PKC ζ 表达与肺腺癌患者生存预后相关（P<0.05）。 结论:肺腺癌组织中PKC ζ 的高表达与肺癌患者出现淋巴结转移相关,有可能作为患者预后不良的指标及潜在的治疗靶点。      

ANGPT1基因在肺腺癌组织中的表达及其预后价值分析

目的:探索血管生成素1（angiopoietin 1,ANGPT1)在肺腺癌组织中的表达及预后意义。方法:从癌症基因组图谱(TCGA)数据库收集肺腺癌和肺鳞癌数据,并下载ANGPT1基因表达谱资料及临床信息资料。采用t检验明确ANGPT1在肺癌组织和正常组织中的表达差异,χ2检验分析ANGPT1基因表达与肺腺癌患者临床病理特征的相关性,Log-rank检验进行生存分析;利用基因集富集分析（Gene Set Enrichment Analysis,GSEA）方法,预测肺腺癌中可能受ANGPT1调控的相关通路。结果:ANGPT1基因在肺癌组织中低表达;其表达水平与T分期（P=0.013)呈负相关;ANGPT1低表达的肺腺癌患者预后明显差于高表达患者（P=0.006）,是影响肺腺癌预后的独立保护因素(P＜0.05)。GSEA结果显示,ANGPT1可能通过调节G2M检查点、DNA损伤修复、凋亡、mTOR信号、MYC信号、有丝分裂纺锤体等细胞增殖相关通路影响肺腺癌的发生发展。结论:ANGPT1是肺腺癌的独立预后保护因素,可能成为肺腺癌的潜在预后标志物和治疗靶点。     

PTPN13和FAK在肺鳞癌中的表达及其临床意义

目的:研究PTPN13和FAK在肺鳞癌中的表达及意义,为建立早期预防、早期诊断、预后预警及个体化治疗的肺鳞癌防治新策略奠定基础.方法:免疫组化法观察PTPN13及FAK在肺鳞癌及癌旁组织中的表达情况.结果:PTPN13表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著负相关(P<0.05);FAK表达与肺鳞癌的临床分期、组织分化程度及淋巴结转移呈显著正相关(P<0.05);PTPN13和FAK在肺鳞癌组织中的表达呈显著负相关(P<0.05).结论:PTPN13基因是肺鳞癌发生相关的抑癌基因,其抑制肿瘤侵袭转移的生物学功能可能与FAK磷酸化有关.     

Claudin-7与Slug在肺鳞癌和腺癌中的表达及其临床意义

背景与目的 Claudins是紧密连接的骨架蛋白,Claudin-7是Claudins家族成员之一。本研究旨在观察Claudin-7和Slug在肺鳞癌和腺癌中的表达及其与临床病理因素的关系,并探讨Claudin-7和Slug的相互关系。方法采用免疫组织化学SP法检测101例原发性肺鳞癌、腺癌组织中Claudin-7和Slug的表达,同时应用Westernblot检测30例新鲜肺癌组织及其配对的癌旁组织中Claudin-7和Slug的表达情况。结果 Claudin-7在肺癌中的表达明显低于正常肺组织,并且与分化程度和淋巴结转移有关(P<0.05),Slug在肺癌中的表达明显高于正常肺组织,除与分化程度和淋巴结转移有关外,还与TNM分期有关(P<0.05),肺鳞癌、腺癌中Claudin-7与Slug的表达具有负相关性(r=-0.566,8)。结论肺鳞癌、腺癌中Claudin-7的低表达与Slug的高表达可能是肺组织恶性转变和转移的有关标志物之一。     

Prognostic Value of PCNA and Mutant p53 Expression in Laryngeal Squamous Cell Carcinoma

The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.     

Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape

IntroductionMolecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes.MethodsPublished immune cell signatures and several lung AD and SCC gene expression data sets, including The Cancer Genome Atlas, were used to examine immune response in relation to AD and SCC expression subtypes. Expression of immune cell populations and other immune related genes, including CD274 molecule gene (CD274) (programmed death ligand 1), was investigated in the tumor microenvironment relative to the expression subtypes of the AD (terminal respiratory unit, proximal proliferative, and proximal inflammatory) and SCC (primitive, classical, secretory, and basal) subtypes.ResultsLung AD and SCC expression subtypes demonstrated significant differences in tumor immune landscape. The proximal proliferative subtype of AD demonstrated low immune cell expression among ADs whereas the secretory subtype showed elevated immune cell expression among SCCs. Tumor expression subtype was a better predictor of immune cell expression than CD274 (programmed death ligand 1) in SCC tumors but was a comparable predictor in AD tumors. Nonsilent mutation burden was not correlated with immune cell expression across subtypes; however, major histocompatibility complex class II gene expression was highly correlated with immune cell expression. Increased immune and major histocompatibility complex II gene expression was associated with improved survival in the terminal respiratory unit and proximal inflammatory subtypes of AD and in the primitive subtype of SCC.ConclusionsMolecular expression subtypes of lung AD and SCC demonstrate key and reproducible differences in immune host response. Evaluation of tumor expression subtypes as potential biomarkers for immunotherapy should be investigated.     

Prognostic Value of KRAS Mutation Subtypes and PD-L1 Expression in Patients With Lung Adenocarcinoma

BackgroundThe prognostic value of different KRAS (Kirsten rat sarcoma viral oncogene) mutation subtypes and their association with programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma (LADC) remain unclear. We examined the association of KRAS mutation subtypes with clinical outcomes and PD-L1 expression status.Patients and MethodsPatients diagnosed with KRAS-mutated LADC were evaluated for PD-L1 expression, cancer staging, overall survival (OS), and relapse-free survival.ResultsA cohort of 254 KRAS-mutated LADC patients (median follow-up, 17 months) was studied. The 3 major subtypes of KRAS mutations were G12C (46.1%), G12V (21.7%), and G12D (15.7%). We found that all these subtypes had no impact on cancer stages, brain metastasis at diagnosis, OS, and relapse-free survival. Among this cohort, 33% of 94 patients who had PD-L1 staining data available had PD-L1–positive disease (≥ 1% of tumor cells). PD-L1 expression status was not significantly different among the 3 major mutation subtypes. Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (median survival, 5.7 vs. 12.8 months, P = .007). In multivariable analysis, PD-L1 positivity remained as an adverse factor for OS, with hazard ratio of 4.44 (P = .0007). PD-L1 status did not affect OS in other subtypes of mutations.ConclusionKRAS mutation subtype is not associated with patient clinical outcomes or PD-L1 expression status. However, PD-L1 positivity appears to negatively affect OS in LADC patients with G12C mutation. Further study is needed to confirm our observation and to determine if programmed cell death 1/PD-L1 antagonist may affect the clinical outcome of patients with different KRAS mutation subtypes.     

Prognostic Value of Ki67 and VE6F Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVE To investigate the prognostic value of measuring Ki67 and VEGF expression in laryngeal squamous cell carcinoma (LSCC). METHODS The expression of Ki67 and VEGF in 32 LSCC tissues was studied by immunohistochemical staining. Of these cases, 5 recurred (recurrent group), 3 cases metastasized (metastatic group), 8 cases died (deceased group) and 24 cased survived (survival group) over a 3 year period of follow-up after their operation. RESULTS The expression of Ki67 and VEGF in the deceased group was higher compared to that in the survival group (P<0.01). Overexpression of Ki67 was found in the recurrent group and in the metastatic group (P< 0.05). VEGF expression was higher in the recurrent group than in the non recurrent group (P<0.05). With Cox-regression of multivariate analysis, Ki67 (RR:3.236; P=0.001), the clinical T stage (RR: 1.382; P=0.029) and metastasis in lymph nodes (RR:0.316; P=0.033) were shown to be independent prognostic factors for survival of LSCC patients. CONCLUSION Ki67 and VEGF expression is related to the prognosis of LSCC. Overexpression of the 2 markers indicated poor prognosis of the disease, a finding which might be helpful for the treatment of laryngocar-cinoma.     

Prognostic Value of MAC30 Expression in Human Pure Squamous Cell Carcinomas of the Lung

Recent evidence haas indicated that meningioma-associate protein (MAC30) exhibits different expression patterns in various tumors. However, little is known about the value of MAC30 in human squamous cell carcinoma of lung (SQCLC). The purpose of our study was to investigate the expression of MAC30 and to explore its clinical significance in SQCLC patients. A total of 156 Chinese patients diagnosed with SQCLC were selected for this study. The expression of MAC30 in all tissues was confirmed by immunohistochemical staining. Quantitative real-time PCR was performed to analyze MAC30 mRNA expression in 32 cases of SQCLC patients with corresponding non-tumor lung tissues. We observed enhanced mRNA expression of MAC30 in SQCLC as compared to control samples. Further, elevated MAC30 protein expression was strongly associated with poor tumor differentiation, TNM stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression demonstrated poor overall survival. Multivariate analysis explicated that increased MAC30 expression was a valuable independent predictable factor for poor tumor differentiation and short survival in SQCLC patients. Our present study suggests that MAC30 may serve as a biomarker for poor tumor differentiation and outcomes of patients with SQCLC.