On the significance of Tim-3 expression in pancreatic cancer

ObjectiveWe aim to explore the connection between Tim-3 expression in both cancerous pancreatic and pericarcinous tissues and the clinicopathological features of pancreatic cancer. We will also preliminarily assess the role and significance of Tim-3 in the diagnosis, treatment, and prognosis of pancreatic cancer.MethodsCancerous pancreatic and pericarcinous tissues from 50 patients with pancreatic cancer and six healthy pancreatic tissues were collected from the pathological specimens of traumatic patients to distinguish Tim-3 expression using immunohistochemistry. Tim-3 expression was observed to be correlated with cell invasion, metastasis, and recurrence of pancreatic cancer.Results1. For the immunohistochemical method, Tim-3 expression in pancreatic cancer tissues was observed to be elevated and statistically significant (P < .01) compared to pericarcinous and normal pancreatic tissues. No statistically significant difference (P > .05) was observed between Tim-3 expression in pericarcinous and normal pancreatic tissues. 2. While Tim-3 expression was observed to be closely related to the history of smoking, fasting blood glucose, tumor size, TNM stage, it was not observed to be related to gender, age, tumor location, pathological type, and degree of tumor differentiation.Conclusion1. Tim-3 expression in pancreatic cancer tissues was high. 2. The high Tim-3 expression in pancreatic cancer tissues may be closely related to cell invasion, metastasis, and the recurrence of pancreatic cancer.     

共刺激分子B7-H4在宫颈癌中的表达及意义

目的:肿瘤微环境中免疫共刺激分子B7-H4与其配体结合后可提供免疫抑制信号,调控肿瘤组织中的免疫应答。本研究探讨B7-H4、Fas及Caspase-3裂解片段在宫颈鳞状细胞癌中的表达及其与临床病理因素的关系,分析其参与肿瘤免疫逃逸的机制。方法:应用免疫组织化学SP法检测23例正常宫颈上皮、38例宫颈上皮内瘤变(CIN)和132例宫颈鳞状细胞癌组织中B7-H4、Fas及Caspase-3裂解片段的表达水平,分析其与宫颈癌各临床病理因素的相关性。结果:B7-H4在正常宫颈上皮组织中不表达,在CIN组织中微弱表达,在宫颈鳞状细胞癌组织中高表达。B7-H4表达与肿瘤的临床分期、淋巴结转移、原发肿瘤大小和肿瘤浸润深度有关,B7-H4与Fas蛋白表达呈现负相关,与Caspase-3裂解片段存在共表达关系。结论:B7-H4在宫颈鳞状细胞癌中过表达可引起Fas蛋白表达下调和Caspase-3裂解片段增多,抑制肿瘤细胞发生凋亡,参与肿瘤逃避宿主的免疫监视,从而促发宫颈癌的发生和发展。阻断B7-H4通路途径,有望成为宫颈鳞状细胞癌治疗的新靶点。     

Immunohistochemical Expression of RAGE and Its Ligand (S100A9) in Cervical Lesions

Altered expressions of receptor for advanced glycation end-products (RAGE) and its ligand (S100A9) are observed in many cancers and play a key role in inflammation-associated cancer. In our previous study, by two-dimensional gel electrophoresis followed by mass spectrometry, the expression of S100A9 protein was found to increase in squamous cervical cancer compared with adjacent normal cervical tissues. Therefore, in the present study we observed the expressions of S100A9 and RAGE in 30 chronic cervicitis, 50 cervical intraepithelial neoplasia (CIN), and 40 squamous cervical cancer (SCC) using immunohistochemical analysis and analyzed the differential expression and possible role of S100A9 and RAGE in cancer development. Immunohistochemical findings were as follows: the expressions of S100A9 and RAGE were demonstrated in chronic cervicitis, CIN, and SCC. Moreover, their expressions were gradually increasing as the tumor progressed. In SCC, the staining scores of S100A9 and RAGE were significantly higher in well-differentiated tumors compared to moderately and poorly differentiated tumors. The expression of S100A9 in epithelial cells exhibited a positive correlation to RAGE expression in chronic cervicitis, CIN, and SCC. There were no significant difference of S100A9 immunoreactivity in stromal cells among chronic cervicitis, CIN, and SCC. Moreover, there was no correlation between S100A9 immunoreactivity in stromal cells of SCC and clinicopathological parameters. Finally, double immunohistochemistry illustrated that RAGE and S100A9 co-express in SCC. In conclusion, RAGE binds its ligand (S100A9), which plays an important role in the development of SCC. In addition, the expressions of S100A9 and RAGE in SCC tumor cells were closely associated with histological differentiation.     

HGF和EZH2在宫颈癌组织中的表达及其与临床病理特征的关系

目的:探讨肝细胞生长因子(HGF)、果蝇zeste基因增强子2(EZH2)在宫颈癌组织中的表达及其与临床病理特征的关系。方法:选取2016年10月到2018年1月期间在新疆医科大学附属肿瘤医院接受治疗的宫颈癌患者50例,收集其手术切除的病理组织作为宫颈癌组的检测标本,另选取同期在我院收治的子宫肌瘤患者,收集其行全子宫切除术时切除的宫颈组织,其中上皮内瘤样病变(CIN)组织和正常宫颈组织各50例,CIN组织作为CIN组的检测标本,正常宫颈组织作为对照组的检测标本。比较宫颈癌组、CIN组和对照组标本中HGF和EZH2的阳性表达情况。分析HGF和EZH2的表达与宫颈癌患者临床病理特征的关系,分析宫颈癌组织中HGF、EZH2表达的相关性。结果:各组标本中的HGF和EZH2的阳性表达率整体比较差异均有统计学意义(P0.05),宫颈癌组、CIN组的HGF和EZH2的阳性表达率均明显高于对照组,且宫颈癌组EZH2的阳性表达率高于CIN组(P0.05)。宫颈癌组织中HGF和EZH2的表达与年龄、肿瘤类型、肿瘤大小无关(P0.05),临床分期II期、有淋巴结转移、病理分级G3的宫颈癌组织中HGF和EZH2的阳性表达率高于临床分期I期、无淋巴结转移、病理分级G1+G2的宫颈癌组织(P0.05)。经Spearman相关分析显示,宫颈癌组织中HGF与EZH2表达呈正相关(P0.05)。结论:HGF和EZH2在宫颈癌组织中呈高表达,且其表达水平与临床分期、淋巴结转移、病理分级有关。     

半乳糖凝集素-3与程序性死亡受体-1在宫颈鳞癌组织中的表达及其临床意义

目的:探讨半乳糖凝集素-3(Gal-3)和程序性死亡受体-1(PD-1)在宫颈鳞癌组织中的表达及其临床意义。方法:选择2016年1月-2017年12月期间我院收治的宫颈鳞癌患者80例纳入观察组,宫颈上皮内瘤变(CIN)患者60例纳入CIN组,取同期在我院进行治疗的宫颈炎患者50例纳入对照组。采集三组患者的宫颈组织标本,采用免疫组化SP法对各组织标本中的Gal-3、PD-1的阳性率、表达水平进行检测,并分析Gal-3、PD-1与宫颈鳞癌临床病理特征的关系以及各指标表达水平的相关性。结果:观察组、CIN组的Gal-3、PD-1的阳性表达率、表达水平均高于对照组,且观察组高于CIN组(P0.05)。Gal-3、PD-1的表达与宫颈鳞癌患者的年龄、病灶大小、分化程度无关(P0.05),而与宫颈鳞癌肿瘤的分期、淋巴结转移有关(P0.05)。经Spearman相关性分析显示,宫颈鳞癌组织中Gal-3与PD-1间表达水平呈正相关性(r=0.496,P=0.000)。结论:Gal-3、PD-1的表达水平与宫颈鳞癌的发生、发展有密切关联,并且两种指标间呈明显正相关。     

MICA/B蛋白在不同宫颈病变组织中的表达及意义

目的:探讨主要组织相容性复合物I类相关蛋白A/B(MICA/B)在不同宫颈病变组织及宫颈细胞系中的表达及定位。方法:采用免疫组织化学SP法检测宫颈炎症组织、高级别鳞状上皮内病变(high-grade squamous intraepithelial lesions, HSIL)及宫颈鳞癌(cervical squamous cell carcinoma, CSCC)组织中MICA/B蛋白的表达情况。采用免疫荧光化学与激光共聚焦显微术结合的方法研究3种宫颈癌细胞系C33a(HPV-)、Siha(HPV16+)、Hela(HPV18+)及正常宫颈上皮细胞系H8中MICA/B的表达和定位。结果:MICA/B蛋白主要表达定位于细胞浆,部分细胞核,在宫颈鳞癌组织中阳性表达率(83.3%、81.8%)高于宫颈炎症组织(39.3%、44.0%),差异具有统计学意义(均有P0.001);MICA蛋白在HSIL组织的阳性表达率(81.8%)高于宫颈炎症组织(39.3%),差异具有统计学意义(P=0.002);与分化程度、临床分期、淋巴结转移等临床病理参数之间比较无统计学差异(P0.05)。结论:MICA蛋白随着宫颈组织病变的加重阳性表达率逐渐增高,MICB蛋白在宫颈癌组织的表达高于宫颈炎症组织。提示MICA/B蛋白可为宫颈癌的诊断及靶向治疗提供新方向。     

microRNA-145表达对宫颈癌Hela细胞增殖及凋亡的影响

目的:探讨微小核糖核酸145(micro RNA-145)表达对宫颈癌Hela细胞增殖及凋亡的影响。方法:实验室常规培养宫颈癌Hela细胞并分为4组,空白(Blank)组(Hela细胞+RPMI1640)、micro RNA-145组(Hela细胞+RPMI1640+micro RNA-145-5p mimics)、阴性序列(NC)组(Hela细胞+RPMI1640+NC)、Mock组(Hela细胞+RPMI1640+Lipofectamine 2000),记录各组Hela细胞转染率,采用实时荧光定量聚合酶链锁反应(QRT-PCR)检测各组Hela细胞中micro RNA-145的表达水平,采用四甲基偶氮唑蓝(MTT)比色法检测Hela细胞增殖情况,采用4',6-二脒基-2-苯基吲哚(DAPI)染色法判断Hela细胞凋亡情况。结果:本研究中,各组Hela细胞转染率均80%;micro RNA-145组micro RNA-145的表达显著高于Blank组、NC组和Mock组,差异有统计学意义(P0.05)。转染24 h、48 h、72 h后,micro RNA-145组490 nm波长处的光密度值(OD490值)较转染0h后明显降低,转染48 h、72 h后,Blank组、NC组、Mock组OD490值较转染0 h后时明显升高,转染24 h、48 h、72 h后,micro RNA-145组OD490值均低于Blank组、NC组、Mock组,差异有统计学意义(P0.05)。DAPI染色后,micro RNA-145组Hela细胞凋亡率高于Blank组、NC组、Mock组,差异有统计学意义(P0.05)。转染后,Blank组、NC组、Mock组的micro RNA-145表达率、OD490值、DAPI染色后Hela细胞凋亡率比较差异均无统计学意义(P0.05)。结论:micro RNA-145表达上调可抑制宫颈癌Hela细胞增殖,并促进Hela细胞凋亡,通过药物调控micro RNA-145表达有望成为宫颈癌治疗的新靶点。     

GRP94和CD8在宫颈病变组织中的表达及意义

目的：探讨葡萄糖调节蛋白94（glucose—regulated protein94,GRP94）和CD8在宫颈病变组织中的表达及与HPV感染的关系。方法：采用免疫组化S—P法检测32例原发宫颈癌、27例宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）及40例慢性宫颈炎组织中GRP94和CD8的表达及定位;采用western blot技术检测6例宫颈癌及6例正常宫颈组织中GRP94和CD8的表达。结果：①在宫颈癌、CIN2／3、CIN1及慢性宫颈炎组织中,GRP94的阳性表达率分别为87．5％、82．4％、40％和22．5％;CD8的阳性表达率分别为28．1％、64．7％、90％和97．5％;GRP94在宫颈癌和CIN2／3中的表达均显著高于慢性宫颈炎和CIN1组织（P均〈0．05）;CD8在宫颈癌组的表达显著低于慢性宫颈炎组、CIN1组及CIN2／3组（P均〈0．05）。②Western blot结果示GRP94在宫颈癌组织中的表达显著高于正常宫颈组织（P〈0．01）;CD8在宫颈癌组织中的表达显著低于正常宫颈组织（P〈0．01）。③GRP94的表达与宫颈癌分化程度、有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期及有无淋巴结转移无关（P〉0．05）;CD8的表达与有无脉管侵袭有关（P〈0．05）,而与年龄、病理类型、临床分期、分化程度及有无淋巴结转移无关（P〉0．05）。④宫颈病变组织中,GRP94的表达与HPV感染呈正相关（rs=0．377,P=0．000）;cD8的表达与HPV感染呈负相关（rs=-0．395,P=0．000）;GRP94与CD8的表达呈负相关（rs=-0．608,P=0．000）。结论：GRP94表达可能是宫颈CIN进展及宫颈癌预后判断的重要预测指标。     

MiR-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用分析

目的:研究Mi R-23a靶向HOXC8在黑龙江省宫颈癌人群中发生的作用及机制。方法:采集从2017年1月～2019年1月,于我院确诊为正常宫颈、宫颈上皮内瘤变(CIN)、宫颈癌患者的病变组织各90例。采用逆转录多聚酶联反应(RT-PCR)法分别检测正常宫颈组织、CIN组织、宫颈癌组织中的Mi R-23a表达水平。此外,通过■转染试剂将Mi R-23a模拟物、Mi R-23a抑制物以及空白对照片段转染至宫颈癌细胞Siha中,检测转染后0 h、48 h、72 h时三组Siha细胞的增殖能力情况。另外,以RT-PCR法检测正常宫颈组织、CIN组织、宫颈癌组织中的HOXC8表达水平。结果:宫颈癌组织中Mi R-23a的相对表达量显著高于CIN组织与正常组织,且CIN组织中Mi R-23a的相对表达量显著高于正常组织(均P0.05)。Mi R-23a模拟物组Siha细胞的增殖能力显著优于Mi R-23a抑制物组与空白对照组,且空白对照组Siha细胞的增殖能力明显优于Mi R-23a抑制物组(均P0.05)。宫颈癌组织中HOXC8的相对表达量显著高于CIN组织与正常组织,且CIN组织中HOXC8的相对表达量显著高于正常组织(均P0.05)。结论:Mi R-23a可能是通过靶向下调HOXC8基因的表达,进一步促进了宫颈癌的发生、发展,这为临床宫颈癌的防治提供了新的靶点,值得临床重点关注。     

宫颈不同疾病患者合并HPV感染的病原菌感染状况及免疫功能

目的 调查分析宫颈不同疾病患者合并人乳头瘤病毒（HPV）感染的病原菌感染状况及免疫功能。方法 选择2015年3月至2018年1月在我院就诊的96例宫颈不同疾病患者为研究组,其中宫颈炎组18例,宫颈上皮内瘤变组54例（CINⅠ组15例,CINⅡ组17例,CINⅢ组22例）,宫颈癌组24例;并以同期在我院进行体检的80例健康女性为对照组,检测所有研究对象的HPV感染、阴道菌群情况和宫颈分泌物CD4+、CD8+细胞数。结果 研究组HPV感染率明显高于对照组（P0.05）。宫颈炎组、CINⅠ组、CINⅡ组、CINⅢ组、宫颈癌组CD4+ T细胞表达阳性率呈下降趋势,宫颈癌组与宫颈炎组、CINⅠ组比较差异有统计学意义（P0.05）;CD4+/CD8+<1患者所占比例呈上升趋势,宫颈癌组、CINⅢ组、CINⅡ组与宫颈炎组比较差异有统计学意义（P<0.05）。结论 HPV感染、病原菌感染及免疫功能下降与宫颈病变发生发展密切相关,临床中应给予足够重视并及时进行有效干预。     

基于免疫组化和癌症基因组图谱数据分析的脾酪氨酸激酶在宫颈癌中的表达研究

摘要 目的：探讨Syk 在宫颈癌中的表达及其临床意义。方法：应用免疫组化检测Syk在宫颈癌、癌前病变(CIN)和相应的正常宫颈组织中的表达。借助R2生物信息平台挖掘Syk在TCGA数据库305例宫颈鳞癌中的mRNA表达及其与预后的关系。结果：免疫组化结果显示,Syk在宫颈癌巢分化较好的中心区表达较强,在分化较低的癌巢周边区表达较弱。Syk 染色主要定位在宫颈癌和正常宫颈组织的细胞质和细胞膜,正常宫颈组织基底细胞无 Syk 表达,8例CIN组织细胞核中可见Syk表达, 但宫颈癌组织细胞核中未见Syk表达。Syk在宫颈癌、CIN和正常宫颈组织中的阳性率分别是76%、54%、40%,三组间的表达差异具有统计学意义（P=0.001）。Syk 在深度浸润和淋巴结转移中表达较强。数据挖掘结果显示,Syk mRNA在305例不同临床分期的宫颈癌中均表达,Syk mRNA高表达组219例,Syk mRNA低表达组73例,其中13例生存数据缺失,Syk高表达组的患者预后较差。结论：Syk在宫颈癌中的表达提示Syk在宫颈癌中具有致癌蛋白的作用,Syk在某些CIN中的核表达可能与更好的预后相关。     

HLA-I表达与维吾尔族妇女宫颈癌前病变及HPV16感染的关系研究

目的：观察人白细胞相关抗原I（human leukocyte antigen class I,HLA-I）表达与维吾尔族妇女宫颈癌前病变进程及高危型HPV16的关系。方法：收集维吾尔族妇女宫颈炎、宫颈内上皮瘤样病变（cervical intraepithelial neoplasia,CIN）和宫颈鳞癌患者的石蜡包埋组织标本共148例,提取组织DNA,应用PCR的方法检测HPV阳性及HPV16型别;同时采用免疫组织化学SP法检测HLA-I蛋白表达水平。结果：（1）在维吾尔族妇女中HLA-I抗原在宫颈炎、CINI-II、CINIII、SCC组中阳性表达逐渐减少,差异有统计学意义（P〈0.001）。（2）HLA-I的阳性表达下降趋势与宫颈癌临床分期、组织分化程度和淋巴结转移密切相关。（3）HPV在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为13%、46%、82%、95%,差异有统计学（P〈0.001）。（4）HPV16在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为4%、30%、68%、85%,差异有统计学（P〈0.001）。（5）在HPV16阳性标本中,存在HLA-I表达缺失的占71%（58/82）,HPV16感染与HLA-I表达呈负相关（r=-0.625,P〈0.001）。结论：（1）HLA-I表达缺陷可能是宫颈病变进展的重要标志,对宫颈癌的预测预警提供依据。（2）HPV16感染在宫颈病变的发展过程中起到了极大的促进作用,是一个很强的致癌因素。（3）HPV16感染与HLA-I表达之间的关系对揭示宫颈癌发病机制提供了客观依据。     

信号转导与转录因子3和表皮生长因子受体在宫颈不同病变组织中的表达及其临床意义

目的:探讨信号转导与转录因子3(STAT3)与表皮生长因子受体(EGFR)在宫颈不同病变组织中的表达变化及其临床意义。方法:采用Western blot与免疫组化的方法检测100例上皮内瘤样病变(CIN)组织、60例宫颈癌组织及40例正常宫颈组织中STAT3与EGFR的表达;分析STAT3与EGFR的表达与宫颈癌组织病理特征的关系;对宫颈癌组织中STAT3与EGFR的表达的相关性进行分析。结果:宫颈癌组织以及CIN组织中STAT3、EGFR的表达量和阳性率显著高于正常宫颈组织(P0.05),且宫颈癌组织中STAT3、EGFR的表达量和阳性率高于CIN组织,差异有统计学意义(P0.05);STAT3与EGFR在宫颈癌组织中的染色强度较正常宫颈组织以及CIN组织显著增强;STAT3与EGFR的异常表达与宫颈癌患者的组织学分级、临床分期以及是否发生淋巴结转移有关(P0.05),而与年龄以及病理分型无关(P0.05);宫颈癌组织中STAT3和EGFR表达呈正相关(P0.05)。结论:STAT3与EGFR表达与CIN、宫颈癌的进展紧密相关,且与宫颈癌部分病理特征相关,二者有可能作为宫颈癌诊断及预后的参考指标。     

Immunohistochemical LRIG3 Expression in Cervical Intraepithelial Neoplasia and Invasive Squamous Cell Cervical Cancer: Association with Expression of Tumor Markers,Hormones, High-Risk HPV-Infection,Smoking and Patient Outcome

The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, menopausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and Ecadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cell cervical cancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influenced by or influences a pattern of tumor markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful.Key words: LRIG3, cervical cancer, cervical intraepithelial neoplasia, biological markers, human papillomavirus, hormonal contraceptives, smoking     

Interferon-β Induced microRNA-129-5p Down-Regulates HPV-18 E6 and E7 Viral Gene Expression by Targeting SP1 in Cervical Cancer Cells

Infection by human papillomavirus (HPV) can cause cervical intraepithelial neoplasia (CIN) and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.     

ProExC在宫颈癌及其癌前病变中的表达及意义

目的：探讨ProExC在宫颈癌及其癌前病变中的表达及意义。方法：应用免疫组织化学SP法检测ProExC在不同宫颈病变组织芯片中的表达。结果：ProExC在宫颈炎、C1NⅠ、CINⅡ、CINⅢ及宫颈癌中的阳性表达率分别是25％,51．7％,77．9％,90％,93．8％,且其表达在宫颈癌及CINⅡI级病变与宫颈炎及CINI级病变相比较差异具有统计学意义（P〈0．05）,ProExC在CINⅠ级组织中表达低于CINⅡ级,差异具有统计学意义（P〈0．05）,ProExC在浸润性宫颈癌中的表达与临床病理因素无关（P〉0．05）。结论：ProExC反映了细胞的增殖活性,促进宫颈癌的发生发展,可作为诊断及监测预后的指标。     

Expression of Prostate-Specific Membrane Antigen in Lung Cancer Cells and Tumor Neovasculature Endothelial Cells and Its Clinical Significance

BackgroundProstate-specific membrane antigen (PSMA) has been found in tumor neovasculature endothelial cells (NECs) of non-prostate cancers and may become the most promising target for anti-tumor therapy. To study the value of PSMA as a potential new target for lung cancer treatment, PSMA expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) tissues and its relationship with clinicopathology were investigated in the current study.MethodsImmunohistochemistry was used to detect PSMA expression in a total of 150 lung specimens of patients with lung cancer. The data were analyzed using univariate and multivariate statistical analyses.ResultsThe percentages of NSCLC patients who had PSMA (+) tumor cells and PSMA (+) NECs were 54.02% and 85.06%, respectively. The percentage of patients younger than 60 years old who had PSMA (+) tumor cells was 69.05%, which was significantly greater than the percentage of patients aged 60 years or older (40.00%, p<0.05). A significant difference was observed in the percentage of NSCLC patients with PMSA (+) NECs and stage I or II cancer (92.98%) and those patients with stage III or IV cancer (76.77%). In the SCLC tissues, NEC PSMA expression (70.00%) did not differ significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all negative. There was no significant correlation between the presence of PSMA (+) NECs in SCLC patients and the observed clinicopathological parameters.ConclusionsPSMA is expressed not only in NECs of NSCLC and SCLC but also in tumor cells of most NSCLC patients. The presence of PSMA (+) tumor cells and PSMA (+) NECs in NSCLC was negatively correlated with age and the clinicopathological stage of the patients, respectively.     

Up-regulation of Foxp3 participates in progression of cervical cancer

Foxp3 was identified as a key protein in mediating inhibitory functions of regulatory T cell (Treg). Foxp3 was thought to express only in the T cell lineage until recently when some researches reported that Foxp3 was also expressed by cancer cells. In this study, we describe for the first time the expression of Foxp3 in cervical cancer. Progression from cervical intraepithelial neoplasia (CIN) to cervical cancer is a multistep process initiated by persistent infection with high-risk human papillomavirus (HPV). P16^INK4a is a crucial marker of HPV integration into host cells. In the present study, expressions of Foxp3 and P16^INK4a in CIN and cervical cancer were detected by immunohistochemistry. Our results found expression level of Foxp3 was increased during the progression of cervical neoplasia. Moreover, up-regulation of Foxp3 appeared to be correlated with the expression of P16^INK4a. Examination of the role of Foxp3 in differentiation by double immunostaining for cytokeratin 10 (CK10) showed significant association between Foxp3 expression and differentiation (Foxp3 vs CK10). Furthermore, positive expression of Foxp3 was correlated with tumor size. These data suggest that Foxp3 may play an important role in differentiation and growth of cervical cancer cells. Our findings provide new insights regarding the role of Foxp3 in differentiation and its association with HPV infection during the development of cervical cancer.     

TLR4在宫颈癌与不同HPV亚型宫颈癌细胞株中表达及意义

目的 探讨TLR4在正常宫颈组织、宫颈上皮不典型增生、宫颈癌组织以及不同HPV亚型宫颈癌细胞株中表达与意义.方法 采用SP免疫组织化（IHC）检测TLR4在12例正常宫颈组织、30例宫颈轻度不典型增生（cervical intraepithelial neoplasia Ⅰ,CINⅠ）、30例宫颈中-重度不典型增生（cervical intraepithelial neoplasiaⅡ-Ⅲ,CIN Ⅱ-Ⅲ）以及49例宫颈癌（invasive cervical carcinoma,ICC）组织中的表达;应用细胞免疫荧光法、逆转录聚合酶链反应（RT-PCR）检测TLR4在不同HPV亚型宫颈癌细胞株HPV18（＋）HeLa、HPV16（＋）Siha以及HPV（-）C33a宫颈癌细胞株上的表达.结果 TLR4的表达随着宫颈病变程度的增高逐渐增强,在正常宫颈组织、CINⅠ、CIN Ⅱ～Ⅲ、ICC中阳性表达率分别为8.33 %（1/12）、20.00 %（6/30）、26.67 %（8/30）和55.10 %（27/49）,ICC与正常宫颈组织、CINⅠ、CINⅡ～Ⅲ之间均有显著性差异（P＜0.01）.TLR4表达与HPV感染有关,在HPV阳性宫颈癌细胞株上表达强于HPV阴性细胞株.结论 TLR4可能参与宫颈癌起始、发展,TLR4的表达与功能与HPV感染有关.