Pluripotency transcription factors and cancer stem cells:small genes make a big difference

Cancer stem cells (CSCs) are thought to drive uncontrol ed tumor growth, and the existence of CSCs has recently been proven by direct experimental evidence, including tracing cel lineages within a grow...     

蛋白酪氨酸磷酸酶基因、血管内皮生长因子在口腔鳞状细胞癌组织中的表达及意义

目的:探讨口腔鳞状细胞癌（OSCC）组织中的蛋白酪氨酸磷酸酶基因（PTEN）、血管内皮生长因子（VEGF）的表达及意义。方法:选取我院2015年4月至2017年9月获取的90例OSCC患者的肿瘤组织标本（OSCC组）和45例癌旁正常口腔黏膜组织标本（对照组）,采用免疫组织化学染色技术检测两组标本中PTEN蛋白、VEGF蛋白的表达情况,并分析不同病理学分级、临床分期、淋巴结转移的OSCC患者肿瘤组织中PTEN蛋白、VEGF蛋白阳性表达差异。结果:OSCC组标本中PTEN、VEGF蛋白阳性表达率分别为35.56%、75.56%,对照组标本中PTEN、VEGF蛋白阳性表达率分别为73.33%、31.11%,两组比较差异具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中PTEN蛋白阳性表达率显著低于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）;在Ⅲ期和Ⅳ期、低分化、发生淋巴结转移的OSCC患者组织中VEGF蛋白阳性表达率显著高于Ⅰ期和Ⅱ期、高分化和中分化、未发生淋巴结转移的OSCC患者,差异均具有统计学意义（P＜0.05）。结论:OSCC组织中PTEN蛋白表达水平显著降低,VEGF蛋白表达水平显著升高,并且与肿瘤的发生发展关系密切。     

干细胞标志物在卵巢癌SKOV3细胞侧群细胞中的表达

目的：检测干细胞相关标志物在卵巢癌SKOV3细胞系侧群（side population,SP）细胞和非侧群（Non-SP）细胞中的表达差异,确定卵巢癌干细胞特异性标志物。 方法： Hoechst 33342染色检测SKOV3细胞中SP细胞的比例,流式细胞术检测SKOV3细胞的SP和Non-SP细胞中干细胞标志物CD133、CD117、CD44、ABCG2、ALDH1 的表达情况,荧光定量PCR检测SP和Non-SP细胞中 ABCG2、ALDH2、NANOG、OCT4、SOX2、CD133、CD117 mRNA的表达水平。 结果： SKOV3细胞中SP细胞比例为(1.56±0.35)%。 ALDH1、ABCG2在SP细胞中表达率分别为（87.3±5.76）%、（29.48±4.43）%,在Non-SP的表达率分别为（5.32±0.47）%、（3.01±1.69）%,差异有统计学意义（ P <0.01）;CD44在这两种细胞亚群中的表达率均高于99%（ P >005）;CD133、CD117在这两种细胞亚群中均不表达。 ALDH1、ABCG2、 NANOG、OCT4和SOX2 mRNA在SP细胞中的表达分别是Non-SP细胞的21.03倍（ P =0.001）、3.14倍（ P =0.001）、23.94倍（ P =0.001）、10.73倍（ P =0.009）和21.46倍( P =0001), CD133、CD117 mRNA在两种细胞亚群中均不表达。 结论： 人卵巢癌细胞株SKOV3中存在SP细胞亚群, ALDH1、ABCG2和NANOG、OCT4、SOX2 mRNA可能是卵巢癌干细胞标志物,为诊断及治疗卵巢癌提供了潜在的靶点。     

口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2的表达及临床意义

背景与目的:近来研究表明Angiopoietin-1、Angiopoietin-2(Ang-1、Ang-2)是极有潜力的血管生长因子,它们与其它血管生长因子之间的局部平衡关系决定了血管是进展、稳定还是衰退。本文探讨Ang-1及Ang-2在口腔鳞癌中的表达及其与临床病理学特征和微血管密度(microvesseldensity,MVD)、血管成熟指数(vesselmaturationindex,VMI)之间的关系,并评估Ang-1及Ang-2的联合表达在肿瘤血管生成及成熟中的作用。方法:用常规免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔粘膜中的Ang-1及Ang-2的表达;通过双标免疫组织化学法同时检测CD34和α-平滑肌肌动蛋白,评估MVD及VMI。结果:口腔鳞癌组织与癌旁正常组织及正常口腔粘膜相比,Ang-2的表达显著增加(51.22%vs.26.67%,0%),而Ang-1的表达显著降低(41.46%vs.90.00%,90.00%),P值均<0.05;在癌旁正常组织与正常口腔粘膜之间,二者的表达没有显著性差异(P均>0.05)。对临床病理因素的分析发现,在高分化肿瘤中Ang-1的阳性率显著高于中分化肿瘤(56.00%vs.18.75%,P<0.05);而Ang-2的阳性率在有淋巴结转移的肿瘤显著高于无淋巴结转移肿瘤(84.62%vs.35.71%,P<0.01)。Ang-1和Ang-2的表达与肿瘤的血管生成及血管成熟密切相关(P值均<0.05)。联合Ang-1和Ang-2的表达发现,Ang-1与Ang-2相互拮抗共同调节肿瘤的血管成熟。结论:口腔鳞癌中Ang-1表达降低及Ang-2表达增高与肿瘤血管的生成及成熟密切相关。     

miR-802及其靶基因ROS1在口腔鳞状细胞癌中的表达及临床意义

目的:研究miRNA-802（miR-802）及其靶基因ROS1在口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）中的表达及潜在临床意义。方法:收集原发OSCC组织及相应癌旁组织标本23例;荧光定量PCR检测各标本中miR-802及ROS1的表达;免疫组织化学检测各标本中ROS1的表达;结合患者临床病理资料,分析miR-802及ROS1在OSCC发生发展中可能的临床意义。结果:与癌旁组织相比较,OSCC组织中miR-802的表达显著降低（P<0.001）,而ROS1的表达显著升高（P<0.01）;相关性分析显示miR-802与ROS1在OSCC中的表达呈显著负相关（r=-0.746,P<0.0001）;miR-802与ROS1的表达水平与患者年龄,性别、肿瘤大小等临床病理特征无显著相关性,而与TNM分期及淋巴结转移有显著相关性（P<0.05）。结论:miR-802通过介导其靶基因ROS1参与调控口腔鳞状癌的发生发展过程。     

癌结节与Ⅲ/Ⅳ期口腔鳞状细胞癌患者病理特征及预后的相关性

目的:分析癌结节在临床Ⅲ-Ⅳ期口腔鳞状细胞癌患者中出现的比率及其与口腔鳞癌患者病理特征和预后的关系。方法:回顾性分析2012年1月-2018年6月山西医科大学第一医院口腔颌面外科诊治的234例临床Ⅲ-Ⅳ期口腔鳞癌患者的资料,采用SPSS 22.0软件包,应用单因素和多因素Logistic回归分析探讨癌结节与患者病理特征的相关性,应用单因素和多因素生存分析探讨癌结节与患者预后的相关性,P＜0.05为差异有统计学意义。结果:234例患者中癌结节阳性率为17.95%（42例）。单因素Logistic回归分析显示,pT分期、pN分期、分化程度、淋巴结比率和脉管癌栓与癌结节的发生具有相关性（P＜0.05）。多因素 Logistic回归分析显示,淋巴结比率和脉管癌栓是癌结节存在的独立危险因素（P＜0.05）。癌结节是影响患者预后的独立危险因素（P＜0.05）,癌结节阳性患者5年生存率显著低于阴性患者（P＜0.05）,死亡风险是癌结节阴性患者的3.836倍（P＜0.05）。结论:癌结节的出现可能与颈淋巴结转移和脉管癌栓有关,癌结节是影响Ⅲ-Ⅳ期口腔鳞癌患者预后的不良特征。     

Altered expression of miR-21 and PTEN in human laryngeal and hypopharyngeal squamous cell carcinomas

Purpose: The purpose of this study was to examine the expression of mir-21 and phosphatase and tensin homologue (PTEN) in laryngeal squamous cell carcinomas (LSCCs) and hypopharyngeal squamous cell carcinomas (HSCCs), and assess correlations between the two as well as with clinical characteristics of patients. Methods: The expression of mir-21 in tumor and adjacent non-tumor tissues was investigated by real-time RT-PCR. Immunohistochemistry (IHC) was carried out to analyze PTEN protein levels. Results: Mir-21 was up-regulated in LSCCs and HSCCs compared to adjacent non-tumor tissues (P < 0.05), and the up-regulated expression of mir-21 was associated with clinical stage (P = 0.001), T classification (P = 0.007), pathologic differentiation (P = 0.025), and lymph node positivity (P = 0.002). In contrast, PTEN IHC staining was notably weaker in tumor tissues than in matched non-tumor tissues (P < 0.05), and the down-regulated expression of PTEN was correlated with tumor staging (P = 0.025), the extent of tumor (P = 0.017), and lymph node positivity (P = 0.040). Furthermore, the level of mir-21 was reversely correlated with PTEN expression (P = 0.006). Conclusion: mir-21 and PTEN might play important roles in the progression of LSCC and HSCC, the two fcators demonstrating a negative correlation.     

miR-212在上皮性卵巢癌中表达的临床意义

目的:本研究探讨上皮性卵巢癌中miR-212的表达及其与临床病理特征的关系。方法:采用茎环实时荧光逆转录聚合酶链反应Real-time RT-PCR检测我院46例上皮性卵巢癌组织及癌旁良性组织中miR-212表达,并对临床病理数据进行分析。Transwell 检测转染miR-212 mimic对SKOV3细胞运动、侵袭的影响,Western Blot检测E-cadherin和Vimentin蛋白表达。结果: 46例上皮性卵巢癌miR-212相对表达量(0.842±0.223)显著低于癌旁卵巢组织(1.212±0.438)。miR-212在Ⅲ/Ⅳ期中相对表达量为(0.865 3±0.469 3),明显低于I/Ⅱ期(1.095 2±0.415 2)（P<0.05)。在低分化癌组织中相对表达量为(0.856 0±0.437 6),明显低于中高分化癌组织(1.131 9±0.471 2)（P<0.05)。而且miR-212在有淋巴结转移组相对表达量为(0.879 4±0.462 2),明显低于无淋巴结转移组（1.163 7±0.412 7)（P<0.01)。但与患者年龄（P=0.430）,肿瘤组织学类型（P=0.546）无关。miR-212转染组SKOV3细胞运动、侵袭均低于未转染组,miR-212转染组抑制SKOV3细胞Vimentin表达,但促进E-cadherin表达。结论:卵巢癌中miR-212低表达,miR-212表达缺失可能与卵巢癌的肿瘤生长和侵袭发展相关,在卵巢癌预后判断中可能有一定价值。     

AEG-1在口腔鳞状细胞癌中的表达及与预后的关系

目的探讨星形细胞上调基因-1（AEG-1）在口腔鳞状细胞癌中的表达及其与临床病理特征和患者预后的关系。方法 应用Western blotting检测AEG-1在口腔鳞癌细胞系（CAL27、SCC4、Tca8113、Tb、Ts）及人永生化表皮细胞HaCaT中的表达;应用免疫组织化学方法检测AEG-1在87例口腔鳞癌和20例正常口腔黏膜组织中的表达,并分析AEG-1表达与口腔鳞癌临床病理特征的关系;采用Kaplan-Meier法进行生存分析,Cox风险比例回归模型分析影响口腔鳞癌患者预后的独立因素。结果 AEG-1在口腔鳞癌细胞系CAL27、SCC4、Ts及Tb中高表达;AEG-1在口腔鳞癌和正常口腔黏膜组织中的高表达率分别为51.7％（45／87）和10.0％（2／20）,差异有统计学意义（P=0.001）。口腔鳞癌的AEG-1表达与分化程度、临床分期、T分期及淋巴结转移有关;生存分析显示,AEG-1低表达组的5年生存率为38.7％,高于高表达组的18.0％,差异有统计学意义（P=0.001）;单因素生存分析显示AEG-1、临床分期、T分期及淋巴结转移为影响口腔鳞癌预后的因素;Cox多因素分析显示AEG 1是影响口腔鳞癌患者预后的独立因素（RR=1.948,95％CI：1.013～3.744,P=0.046）。结论 AEG-1过表达与口腔鳞癌的发生、发展密切相关,可作为判断口腔鳞癌恶性程度和不良预后的参考指标。     

SOX2、C-Myc在晚期食管鳞状细胞癌组织中的表达及其临床意义

目的:探讨SOX2、C-Myc在晚期食管鳞状细胞癌组织中的表达情况及其与临床病理参数的关系。方法:收集我院病理科2008-2014年间64例晚期食管鳞状细胞癌患者资料,采用免疫组织化学EnVision法检测SOX2、C-Myc的表达情况。结果:64例晚期食管鳞癌患者中：男性51例(79.7%),女性13例(20.3%),男性患者远多于女性患者。发生了淋巴结转移的患者有44例,转移率为68.8%。患者远处转移率为51.6%(33/64),常见的转移部位有肺、肝、骨、胃、支气管等。免疫组化显示SOX2、C-Myc均定位于细胞核,二者在晚期食管鳞癌组织中的阳性率分别为51.56%、25%。高表达的SOX2与远处转移密切相关（P=0.046）,而与其他病理参数无关;C-Myc表达升高与TNM分期密切相关（P=0.018）,而与其他病理参数无关。SOX2、C-Myc蛋白共表达与晚期食管鳞癌的TNM分期（P=0.020）、N分期（P=0.027）密切相关。结论：在晚期食管鳞状细胞癌中,高表达的SOX2与远处转移密切相关,希望能成为新的治疗靶点。     

The Clinical and Prognostic Implications of Pluripotent Stem Cell Markers Expression and Their Correlation with the WNT signal pathway in Hepatocellular Carcinoma

Objectives: This study aimed to investigate the expression of SOX2, SOX9, p53, and β-catenin in hepatocellular carcinoma (HCC) and their correlation with clinicopathological parameters of prognostic importance. Materials and Methods: Seventy-five patients were enrolled in this study. All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors and patient survival. Results: We detected the positive expression of SOX2, SOX9, p53, and β-catenin in 76%, 50.7%, 50.7%, and 77.9% of HCC specimens respectively. All studied markers showed a significant increase in the expression in tumor tissue specimens compared to non-tumor tissue. Both SOX2 and SOX9 expressions were significantly associated with adverse prognostic factors in HCC. Significant positive correlations were found between SOX2 and SOX9 and both p53 and β-catenin expression (r= 0.528, 0.485 and; r = 0.253, 0.327, respectively; p < 0.0001 for both of them). Regarding survival, we found that HCC patients with positive SOX2 and SOX9 expressions had significantly shorter overall survival (p=0.0001, each). Additionally, larger tumor size, tumor grade, high stage, tumor multiplicity, presence of cirrhosis, tumor necrosis, high p53 expression, and positive β-catenin expression were independent predictors of worse survival. A multivariate Cox analysis revealed that tumor grade, stage, p53, and SOX2 expression were independent predictors of unfavorable prognosis in overall survival (p=0.0001, p=0.0001,p=0.033; and p=0.003, respectively). Conclusions: Our findings might provide an insight into SOX2 and SOX9’s role in HCC and suggest that SOX2 might be targeted for HCC therapy.     

Survival in squamous cell carcinoma of the oral cavity: differences between pT4 N0 and other stage IVA categories

BACKGROUND: According to the American Joint Commission on Cancer (AJCC, 5(th) edition) classification system, pT4 N0 oral cavity squamous cell carcinoma (OSCC) qualifies for stage IVA status, with its implied poor prognosis. However, preliminary observations suggested that patients with pT4 N0 OSCC might have better survival than other stage IVA categories. The authors sought to identify accurate prognosticators in patients with stage III/IVA OSCC. METHODS: The authors retrospectively reviewed 513 consecutive patients with stage III/IVA OSCC who were undergoing radical surgery. Survival was plotted by Kaplan-Meier analysis. RESULTS: One hundred seventy-eight patients were in stage III, and 335 were in stage IVA. The 335 stage IVA patients were divided into pT4 N0 (n = 105) and pT4 N1/TAny N2 (NO pT4 N0 M0, n = 230). By univariate analysis, 5-year neck control rates (P < .0001), distant metastases (P < .0001), disease-free survival rates (P < .0001), and overall survival rates (P < .0001) were significantly different in pT4 N0 compared with NO pT4 N0 patients. No significant difference in survival between pT4 N0 stage IVA and pstage III could be shown. Multivariate analysis for overall survival demonstrated that the following factors were independently associated with pT4 N0: tumor depth >or=35 mm, vessel invasion, lymph invasion, and perineural invasion. In contrast, tumor depth >or=25 mm, treatment with surgery alone, poor differentiation, extracapsular spread, and pathological nodal metastases (>or=8 lymph nodes) were independent predictors of overall survival in NO pT4 N0. CONCLUSIONS: In patients with stage IVA OSCC (AJCC, 1997), the survival rates for pT4 N0 are better than those for NO pT4 N0 and similar to those of patients with pstage III.     

口腔鳞癌组织中Survivin蛋白的表达及与血管生成的关系

背景与目的:Survivin蛋白主要通过抑制Caspase-3、Caspase-7阻断细胞凋亡过程,在多种常见恶性肿瘤组织中有表达。本研究拟探讨Survivin在口腔鳞癌发生发展中的作用及与血管生成的关系。方法:采用免疫组织化学SP法,检测8例正常口腔粘膜、14例上皮异常增生性白斑、47例鳞癌组织中Survivin的表达及鳞癌中CD34的表达,并计数微血管密度(MVD),分析口腔鳞癌中Survivin与MVD及临床病理特征的关系。结果:Survivin在正常口腔粘膜、异常增生性白斑及鳞癌组织中的阳性率分别为0%(0/8)、14.29%(2/14)和55.32%(26/47);经免疫组化半定量分析,鳞癌组Survivin表达强于正常口腔粘膜组及异常增生性白斑组(P<0.05),而后两组间无显著差别(P>0.05)。Survivin在中-低分化鳞癌组中的表达强于高分化鳞癌组(P<0.05);在有淋巴结转移组中的表达(71.43%)高于无淋巴结转移组(38.89%)(P<0.05)。口腔鳞癌中,随Survivin表达增强(-, ,2 ,3 ),MVD逐渐增高(分别为25.87±12.10,28.70±7.69,35.42±10.09,41.13±9.62)(P<0.05)。结论:Survivin蛋白在口腔鳞癌组织中表达上调;Survivin与口腔鳞癌的分化程度、淋巴结转移有关,并与MVD关系密切,提示Survivin与口腔鳞癌的发生发展过程有关。     

诱导型一氧化氮合酶在口腔鳞癌中的表达及其意义

[目的]探讨口腔鳞癌（OSCC）诱导型一氧化氮合酶（iNOS）的表达与OSCC生物学行为之间的关系。[方法]采用免疫组化法检测10例正常口腔黏膜、17例口腔乳头状瘤、32例鳞状细胞癌组织中iNOS的表达。[结果]①正常121腔黏膜组织不表达iNOS，口腔乳头状瘤和鳞癌中iNOS表达阳性率分别为58．82％和78．12％，三组间比较差异有显著性（P〈0．001）。②高、中、低分化口腔鳞癌组织中iNOS表达阳性率分别是61．54％、88．89％、90．0％（P〉0．05）；iNOS表达与口腔鳞癌的病理分级呈正相关（r=0．3）。③iNOS表达阳性率在Ⅲ-Ⅳ期组、有颈淋巴结转移组中分别明显高于Ⅰ～Ⅱ期组、无颈淋巴结转移组（P〈0．05）。④iNOS阴性表达的口腔鳞癌患者3年生存率（83．33％）明显高于阳性者的27．27％（P=-0．022）。[结论]iNOS产生的一氧化氮（NO）可能在口腔鳞癌的发生、发展中起重要作用；口腔鳞癌组织中iNOS表达与其病理分级、TNM分期、颈淋巴结转移及预后关系密切。