TIPE1在皮肤鳞状细胞癌中的表达及意义

目的:研究TIPE1在皮肤鳞状细胞癌中的表达变化情况。方法:采用免疫组化方法检测31例皮肤鳞状细胞癌组织和31例正常皮肤组织中TIPE1的表达情况。结果:在正常皮肤组织中,TIPE1弱表达于表皮基底层及棘层下部,在表皮全层表达的阳性率为23.20%。在皮肤鳞状细胞癌中,可见TIPE1高表达于大部分的癌细胞中,阳性率为77.41%。TIPE1在皮肤鳞状细胞癌中的表达显著高于正常皮肤组织(P＜0.05)。结论:TIPE1可能参与皮肤鳞状细胞癌的发生和发展。     

气球状细胞痣的病理诊断及鉴别诊断

目的:探讨皮肤气球状细胞痣的病理诊断及鉴别诊断。方法:对1 例皮肤气球状细胞痣应用免疫组化SP（streptavidin-perosidase）法观察,并进行临床病理分析。结果:皮肤组织真皮内见胞浆透亮的细胞排列成大小不等由胶原纤维分隔的小叶,痣细胞绝大部分为体积较大、胞质丰富且呈透明状或细颗粒状气球状痣细胞。胞核小而圆,大小一致,多位于细胞的中央,无异型性及核分裂像。免疫组化染色提示气球状细胞痣S-100(++)、Vimentin(++)、Melan-A（++）、Ki-67＜5%,HMB-45仅在真皮浅层的灶性气球状细胞浆呈弱阳性表达。结论:气球状细胞痣极为罕见,需要与皮肤的多种透明细胞肿瘤进行鉴别,正确诊断主要依赖组织病理及免疫组化结果。     

胃癌及其癌前病变组织Yes相关蛋白和Survivin的表达及其意义

目的:检测YAP和Survivin的表达水平,探讨YAP及Survivin表达与胃癌发生的关系和意义。方法:采用PV9000免疫组化方法分别检测98例胃癌及配对正常胃黏膜,58例肠上皮化生,32例不典型增生组织中YAP和Survivin的表达水平。结果:YAP在不典型增生(37.5%)、胃癌组织(48.0%)中的阳性表达率显著高于正常胃黏膜组织(13.3%),P<0.01;Survivin在肠上皮化生(53.4%)、不典型增生(59.4%)及胃癌(65.3%)组织中的阳性表达率显著高于正常胃黏膜组织(11.2%),P<0.01;弥漫型胃癌组(74.6%)Survivin阳性表达率显著高于肠型胃癌组(51.3%),P<0.05。伴淋巴结转移胃癌组Survivin阳性表达率(76.9%)显著高于无淋巴结转移组(41.2%),P<0.01。在98例胃癌组织中YAP与Sur-vivin表达呈正相关,等级相关系数rk=0.246,P<0.01。结论:YAP可能诱导凋亡抑制因子Survivin的表达,Survivin可能通过抑制胃癌中细胞凋亡及调节细胞有丝分裂的发生进而参与胃癌的发生、发展及转移。将两指标联合检测,有助于...     

Yes相关蛋白在小细胞肺癌中的表达及意义

目的:探讨YAP(Yes-associated protein,YAP)蛋白在小细胞肺癌组织中的表达及其临床意义.方法:应用免疫组织化学检测106例小细胞肺癌组织标本和25例癌旁组织标本,分析其与患者临床病理特征及预后的关系.结果:小细胞肺癌组织中YAP阳性表达率为68.9%(73/106),癌旁组织中YAP阳性表达率为12%(3/25),差异具有统计学意义(P<0.05).在小细胞肺癌组织中,YAP表达与临床分期(P=0.021)、淋巴结转移(P=0.032)、转移病灶数目(P=0.007)、血清NSE水平(P=0.034)和血清LDH水平(P=0.037)有关.单因素生存分析显示,临床分期(P<0.001)、淋巴结转移情况(P=0.018)、病灶转移数目(P=0.004)、心包浸润(P=0.009)、血清NSE水平(P=0.01)、血清LDH水平(P=0.008)和YAP表达(P=0.001)与预后相关.进一步多因素分析显示,临床分期(P=0.001)、淋巴结转移(P=0.012)、心包浸润(P=0.009)和YAP表达(P=0.003)为总生存期的独立预测因子.结论:YAP在小细胞肺癌中具有较高的表达率,其表达情况与肿瘤的进展密切相关.YAP 蛋白表达可作为判断小细胞肺癌患者预后的一个预测指标.     

Linc00961在恶性黑素瘤中表达及其对细胞侵袭及转移的影响

目的:检测潜在长链非编码RNA Linc00961在恶性黑素瘤组织及细胞中的表达,及其对恶性黑素瘤A375细胞迁移和侵袭能力的影响。方法:采用聚合酶链式反应方法检测恶性黑素瘤组织及细胞中Linc00961的表达水平;分析Linc00961在不同TNM分期恶性黑素瘤组织中的表达;构建Linc00961过表达慢病毒质粒上调A375细胞中Linc00961表达,细胞划痕实验检测Linc00961对A375细胞迁移距离的影响,Transwell实验检测Linc00961对A375细胞迁移侵袭的影响。结果:Linc00961在恶性黑素瘤组织及A375细胞中的表达低于良性痣及正常黑素HEMa-LP细胞。TNM IV期恶性黑素瘤组织中的Linc00961表达水平显著低于TNM I、II、III期。过表达A375细胞中Linc00961后,细胞迁移距离降低,细胞迁移及侵袭数目减少（P<0.05）。结论:Linc00961在恶性黑素瘤组织及细胞中低表达,并可抑制恶性黑素瘤细胞迁移及侵袭。     

YAP及磷酸化YAP在胃腺癌中的表达及意义

目的:探讨YAP及磷酸化YAP在胃腺癌组织中的表达及其与胃腺癌发生发展的关系。方法:在60例胃腺癌患者中,应用免疫组化检测YAP及磷酸化的YAP蛋白在胃腺癌组织、癌旁正常组织中的表达情况。利用siRNA抑制细胞中YAP蛋白的表达,MTT检测胃腺癌细胞的增殖能力。结果:YAP蛋白可同时表达于细胞浆及细胞核中,而磷酸化的YAP主要表达于细胞浆中。与正常胃组织相比,胃腺癌组织中YAP蛋白的表达明显升高(P<0.05),而磷酸化的YAP却显著减少(P<0.05)。胃腺癌YAP的表达与患者性别、年龄、肿瘤的分级及分期无相关性,而与胃癌瘤体大小相关(P<0.05)。利用siRNA抑制YAP表达可显著降低胃腺癌细胞的增殖能力。结论:胃腺癌中YAP的高表达及磷酸化YAP的低表达可能参与了胃癌的发生发展。     

长链基因间非编码RNA 00681竞争性结合miR-16促进黑素瘤细胞侵袭和迁移

目的:检测长链基因间非编码RNA 00681（long intergenic noncoding RNA 00681,linc00681）在恶性黑素瘤组织和皮肤良性痣组织中的表达，探索沉默linc00681对黑素瘤A375细胞侵袭和迁移能力的影响及机制。方法:采用一步法实时定量聚合酶链式反应（real time-quantitative polymerase chain reaction，RT-qPCR）检测恶性黑素瘤组织和A375细胞中linc00681的表达。利用小干扰RNA技术沉默黑素瘤A375细胞中linc00681的表达。应用划痕实验检测敲低linc00681对细胞迁移距离的影响，Transwell检测敲低linc00681对细胞迁移和侵袭能力的影响。生信分析网站分析linc00681和微小RNA-16（microRNA-16，miR-16）的潜在结合位点。荧光素酶报告实验检测linc00681与miR-16的结合能力。挽救实验检测miR-16对linc00681调控A375细胞迁移和侵袭能力的影响。结果:黑素瘤组织和A375细胞中linc00681的表达高于皮肤良性痣和正常黑素HEMa-LP细胞。沉默linc00681表达后，A375细胞迁移距离、迁移和侵袭细胞数目均显著降低。研究显示:linc00681可吸附结合miR-16；linc00681和miR-16共同沉默组侵袭和迁移能力明显高于linc00681单独沉默组。结论:linc00681在黑素瘤组织和A375细胞中表达升高，并可通过竞争性结合miR-16促进黑素瘤细胞迁移和侵袭。     

YAP蛋白在结肠癌中的表达及其对SW480细胞增殖和侵袭的影响

目的:研究YAP蛋白在结肠癌中的表达及临床意义, 并初步探讨其对结肠癌细胞增殖、侵袭的影响。方法:免疫组化检测YAP蛋白在25例结肠癌组织及配对正常组织中的表达,并分析其与结肠癌临床病理特征之间的关系;用Real-Time PCR和 Western blot验证YAP-shRNA慢病毒载体转染效率;生长曲线实验和MTT法检测下调YAP表达对结肠癌细胞SW480增殖的影响;Transwell实验检测下调YAP表达对结肠癌细胞SW480侵袭的影响;Western blot检测下调YAP表达对CyclinD1、E-cadherin及Vimentin蛋白的影响。结果:YAP在结肠癌组织中的表达显著高于正常结肠组织（P＜0.05）,并且与淋巴结转移密切相关(P＜0.05);转染YAP-shRNA慢病毒载体的SW480细胞YAP的表达在mRNA 和蛋白水平明显降低（均P＜0.05）;下调YAP表达后结肠癌细胞增殖及侵袭明显减弱（均P＜0.05）;下调YAP 表达可抑制结肠癌细胞CyclinD1、E-cadherin及Vimentin蛋白的表达（均P＜0.05）。结论:YAP在结肠癌组织中高表达,且与淋巴结转移相关,下调YAP表达可抑制结肠癌细胞增殖及侵袭能力,预示YAP在结肠癌恶性进展中具有重要的作用。     

RIPK3在皮肤基底细胞癌中的表达及意义

目的:研究RIPK3在皮肤基底细胞癌中的表达及意义。方法:应用免疫组化SP法检测皮肤基底细胞癌和正常皮肤组织中RIPK3蛋白的表达情况。用RIPK3特异性siRNA干扰RIPK3在原代表皮角质形成细胞HEKa中的表达,用Annexin V-FITC/PI双染法检测细胞凋亡的变化。结果:在所收集的正常皮肤组织中,RIPK3的阳性表达率为90.0%,而在皮肤基底细胞癌皮损中其表达呈明显下降,阳性率为7.5%,两组RIPK3蛋白的阳性表达率及表达强度的差异均具有统计学意义（P<0.001）。HEKa细胞特异性敲低RIPK3表达后细胞凋亡数量减少。结论:RIPK3在皮肤基底细胞癌中的表达显著低于正常皮肤组织,RIPK3在皮肤基底细胞癌中的异常表达可能是通过抑制细胞程序性死亡而在其发生发展过程中起作用。     

Cortactin及FAKPY397在非小细胞肺癌中的表达及关系

目的:探讨皮层肌动蛋白(cortactin)及磷酸化黏着斑激酶(focal adhesion kinase PY397,FAKPY397)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达情况及与临床病理因素之间的关系。方法:采用免疫组织化学方法检测114例NSCLC及相应癌旁正常肺组织中cortactin及FAKPY397的表达情况。结果:Cortactin在正常肺组织中表达阳性率为19.3%(22/114),显著低于其在NSCLC组织中的阳性率为57.9%(66/114,P<0.001)。Ⅲ、Ⅳ期组中cortactin表达阳性率为78.8%(26/33)显著高于Ⅰ、Ⅱ期组的49.4%(40/81,P=0.004),有淋巴结转移组中cortactin阳性率为74.0%(37/50)显著高于无淋巴结转移组的45.3%(29/64,P=0.002)。FAKPY397在正常肺组织中表达阳性率为25.4%(29/114),显著低于其在NSCLC组织中的阳性率为52.6%(60/114)。Ⅲ、Ⅳ期组中FAKPY397的表达阳性率为69.7%(23/33)显著高于Ⅰ、Ⅱ期组中的阳性率为45.7%(37/81,P=0.020),有淋巴结转移组中FAKPY397阳性率为64.0%(32/50)显著高于无淋巴结转移组的43.8%(28/64,P=0.032)。Speaman相关性分析表明在NSCLC中,cortactin的表达与FAKPY397的表达呈正相关(r=0.436,P<0.01)。结论:NSCLC中cortactin的表达与FAKPY397的表达呈正相关,二者协同表达可能是促进NSCLC进展的因素之一。     

Association of early malignant melanoma with nevocytic nevi

The percentage of histologically associated malignant nevocytic nevi is essential for establishing concepts of histogenesis. The literature abounds with studies of this association. However, the results are conflicting and vary between 4% and 72% of malignant melanomas with associated nevocytic nevi with a maximum frequency between 20% and 30%. These different values could be partially explained by the fact that tumors in more advanced stages might have "overgrown" preexisting nevocytic cells. For this reason, only cases of early stage malignant melanoma (tumor thickness less than or equal to 1.5 mm; level of invasion less than or equal to III) were included in this study (n = 150). Thirty-three (22%) of 150 cases of malignant melanoma were associated with nevocytic nevi. In an additional 6.1% of the cases there was a possible but doubtful association. In 45.4% of the cases the nevus cells could be detected below the tumor, in 18.2% they could be seen at the laterally adjacent sides, and in 36.4% they were found at both sites. Fifty percent showed junctional activity from the nevocytic nevi located to the side of the melanoma. We conclude that the finding of approximately 27% of nevocytic nevi with junctional activity among the nevocytic nevi associated with malignant melanoma could be an indicator that at least some malignant melanomas develop within or next to a preexisting and still proliferating nevocytic nevus.     

Common phenotypic expression of gangliosides GM3 and GD3 in normal human tissues and neoplastic skin lesions.

The expression of gangliosides in non-malignant tissues (epidermis and pigmented nevus) and neoplastic lesions (melanoma, squamous cell carcinoma [SCC] and basal cell carcinoma [BCS]) of the human skin was analyzed immunohistochemically and biochemically to characterize the features associated with malignancy. Immunohistochemical staining with an anti-II3NeuAc-LacCer (GM3) monoclonal antibody (M2590 mAb) and an anti-II3(NeuAc)2-LacCer (GD3) mAb (R24) showed the expression of the gangliosides GM3 and GD3 to vary among the different tissues. M2590 clearly stained epidermal keratinocytes and the tumor cells of BCC and SCC, and strongly stained melanocytes and melanoma cells. In contrast, R24 did not stain epidermal keratinocytes and only faintly stained SCC cells, while it clearly stained BCC cells, and intensely stained melanocytes and melanoma cells. GM3 showed a similar level of staining among the tissue specimens, while the level of GD3 staining was quite variable among the tumor specimens. Biochemical analysis by thin-layer chromatography (TLC) with resorcinol staining and TLC immunostaining with either M2590 or R24 showed both GM3 and GD3 to be commonly expressed by both the normal and malignant skin tissues, including SCC. There was no close correlation between the intensity of immunohistochemical staining and the biochemically detected amounts of these gangliosides. This may have been partly due to the so-called cryptic expression of cell membrane gangliosides. Our results thus suggest that analysis of the tumor-associated expression of gangliosides requires several methods, since the sensitivity of the methods used may have a considerable effect on the diagnostic value of gangliosides as skin cancer markers.     

Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma

Expression of the gangliosides GM3, GD3 and GD2 was studied in tissue sections from 19 naevi, 29 primary and 83 metastatic melanoma using the ABC immunoperoxidase technique. GM3 was not detected in normal skin whereas GD2 was detected on the basal and stratum spinosum of the epidermis and on peripheral nerves in the dermis. GD3 was expressed on melanocytes but not on most other components of normal skin. However, GD3 was strongly expressed on epidermis adjacent to naevi and primary melanoma whereas GD2, in contrast to that in normal skin, was not expressed on the epidermis adjacent to 26/29 primary melanoma. All naevi were positive for GM3 and GD3 except that GM3 was not detected on junctional components of naevi. GD2 was not expressed on naevi except in areas showing neuroid differentiation. Studies on melanoma revealed that approximately 60% of primary and 75% of metastatic melanoma expressed GM3 to a varying extent. With 2 exceptions, all primary and metastatic melanomas expressed GD3 although there was variable expression within most of the individual tumours. GD2 was detected in only approximately 25% of primary and 50% of metastatic melanomas. Both GD2 and GD3 were detected on lymphocytes surrounding melanoma. The higher expression of GD2 on metastases compared to primary melanomas was consistent with the view that GD2 expression was associated with increased metastatic potential. However, the low proportion of metastases expressing GD2 and the absence of any correlation with thickness of the primary tumour suggested that GD2 expression was not a reliable marker of metastatic potential. No differences could be detected in ganglioside expression on metastases in skin or lymph nodes. These results appear to have implications for the use of MAbs against gangliosides in therapy of melanoma and in the study of melanocytic differentiation.     

Angiomotin基因沉默增强乳腺癌干细胞特性及其机制探讨

目的:研究Angiomotin(Amot)基因沉默后对乳腺癌干细胞特性的影响,初步评估Amot在乳腺癌中异常表达的分子机制。方法:运用免疫组化、Western blot及RT-qPCR技术在乳腺癌组织及乳腺癌细胞株中验证Amot的表达,进而运用RNA干扰技术特异性地阻断Amot在乳腺癌高表达细胞株MCF-7中的表达,以期了解Amot沉默后对乳腺癌干细胞特性的影响。结果:114例乳腺癌组织中,97例阳性表达,阳性率达85.09%;92例非癌组织中,阳性表达10例,阳性率为10.87%,两组差异具有显著统计学意义（P＜0.001）。Amot在乳腺癌组织中高表达,定位在细胞核和胞浆中,主要定位于细胞核;组织芯片癌旁组织中低表达。MCF-7细胞系经Amot沉默后,细胞形态学上发生上皮间质表型转化。Amot基因沉默后,乳腺癌MCF-7干细胞相关分子表型标志CD24/CD44双标阳性率的变化:CON组:CD24（11.1±0.55）%、CD44<（0.1±0.48）%;NC组:CD24（12.4±0.62）%、CD44<（0.08±0.7）%;KD组:CD24<（0.1±0.08）%、CD44（81.0±2.02）%。乳腺癌干细胞相关分子表型标志物CD24表达降低,CD44表达明显增强,差异有统计学意义（P＜0.001）。肿瘤球形成率:CON组2.6%,NC组2.8%,KD组9.75%;乳腺癌细胞在Amot沉默后形成“肿瘤球”能力增强,差异具有统计学意义（P＜0.01）。干细胞特性相关基因C-myc、Sox-2表达增加;上皮蛋白E-cadherin表达减弱,间皮蛋白N-cadherin、Vimentin、a-SMA、Snail表达明显增加,差异均有统计学意义（P＜0.05）。同时发现,MCF-7细胞系经Amot 沉默后,Hippo-YAP通路中YAP及YAP/TAZ表达降低,YAP上游LATS1表达降低,差异有统计学意义（P＜0.01）。结论:Amot基因沉默增强乳腺癌干细胞特性,诱发乳腺癌细胞发生EMT。     

YAP和TAZ在骨肉瘤组织中的表达及临床意义

目的:探究YAP和TAZ在人骨肉瘤组织中的表达及其与临床病理之间的相关性。方法:使用免疫组织化学方法对47例骨肉瘤组织及20例骨软骨瘤组织中的YAP和TAZ进行检测。结果:YAP在骨肉瘤和骨软骨瘤中的阳性表达率分别为74.5%和30%。TAZ在骨肉瘤和骨软骨瘤中的阳性表达率分别为59.6%和15%。YAP与骨肉瘤的大小（P＜0.05）有关;而TAZ则与骨肉瘤的远处转移及Ennecking分期有关（P＜0.05）。结论:YAP和TAZ在恶性骨肉瘤中的高表达,预示着YAP和TAZ参与了肿瘤的发生发展及骨肉瘤的远处转移,为治疗骨肉瘤及骨肉瘤肺部转移提供了新的思路,为研制治疗骨肉瘤药物提供新靶点。     

YAP及Src在胃癌组织中的表达及临床意义

目的:探讨胃癌患者肿瘤及癌旁组织中YAP、Src的表达差异,分析肿瘤组织中YAP、Src表达与临床病理特征的关系和二者表达的相关性。方法:收集青海省人民医院2020-2022年确诊的胃癌患者61例,从中采集肿瘤组织61例、癌旁组织40例,应用免疫组织化学方法检测肿瘤组织及癌旁组织中YAP、Src的表达,分析二者的表达及相关性,并结合临床病理学资料进行统计学分析。结果:肿瘤组织中YAP、Src表达的阳性率（95.1%、83.6%）明显高于癌旁组织（30.0%、27.5%）（均P＜0.01）。肿瘤组织中YAP的表达与患者的年龄、民族、分化程度、浸润深度、脉管侵犯、神经侵犯、Ki67阳性指数相关（均P＜0.05);Src的表达与患者民族、肿瘤部位、浸润深度、神经侵犯、Ki67阳性指数、HER-2状态相关（均P＜0.05);肿瘤组织中YAP、Src表达呈正相关（r=0.514,P＜0.01）。结论:胃癌患者肿瘤组织中YAP、Src处于过度表达状态,YAP与Src的表达呈正相关;二者高表达与胃癌患者部分不良临床病理特征密切相关。     

酪蛋白激酶1基因在恶性黑色素瘤中的表达及临床意义

目的 研究酪蛋白激酶-1( CK1)在恶性黑色素瘤细胞及组织中的表达并探讨其临床意义.方法 采用qRT-PCR检测CK1 mRNA在恶性黑色素瘤细胞及正常黑色素细胞中的表达.Western blot检测CK1蛋白在恶性黑色素瘤细胞及正常黑色素细胞中的表达.应用免疫组织化学方法检测59例恶性黑色素瘤及30例色素痣标本中CK1的表达.结果 恶性黑色素瘤细胞及组织中CK1基因表达明显高于在黑色素细胞及色素痣组织中的表达,差异有统计学意义(P＜0.05).结论 CK1基因在恶性黑色素瘤细胞及组织中高表达揭示CK1可能与恶性黑色素瘤的发病机制相关.以CK1为靶点的抑制剂或反义基因治疗黑色素瘤可能会展示广阔的前景.     

YAP蛋白在甲状腺髓样癌组织中的表达

目的：探讨YAP蛋白在甲状腺髓样癌（ MTC）发生发展中的作用及临床意义。方法采用免疫组织化学方法检测25例MTC、25例正常甲状腺组织中YAP蛋白的表达。结果25例MTC组织中YAP蛋白阳性表达率为88.00%（22/25）,而25例正常甲状腺组织中YAP蛋白表达均为阴性,比较差异有统计学意义（χ2=39.286,P〈0.05）。结论 YAP蛋白在MTC组织中呈明显过表达,在MTC的发生发展中可能起着重要作用,且有望成为具有潜在应用价值的分子标记及治疗靶点。