肾透明细胞癌差异表达基因及蛋白互作网络分析

目的通过分析肾透明细胞癌及癌旁组织基因芯片数据筛选潜在肿瘤生物标志物.方法从数据库下载肾透明细胞癌芯片数据集GSE6344;利用R语言程序包对原始数据进行预处理并筛选差异表达基因;通过DAVID对差异表达基因进行GO分析;通过R语言的clusterProfiler进行KEGG分析;利用STRING在线软件分析差异基因表达蛋白之间的相互作用,通过Cytoscape按照节点数筛选关键基因.结果通过分析获得229个符合条件的差异表达基因,其中与癌旁组织相比有117个基因上调,112个基因下调.GO分析显示差异表达基因主要参与细胞内信号级联放大、离子转运、损伤应答、脉管系统发育、细胞迁移等生物过程.KEGG分析显示差异表达主要富集在Rap1、MAPK和HIF-1等信号通路.通过蛋白互作网络筛选出EGFR、FLT1、ERBB4、EDN1和ALDOA等关键基因.结论通过对差异表达基因进行生物信息学分析有助于对肾透明细胞癌病因和潜在分子机制的理解,筛选出的核心基因可能成为早期诊断标志物及治疗靶点.     

多囊性肾透明细胞癌的病理学诊断

目的：探讨多囊性肾透明细胞癌的临床病理特点。方法：对1例多囊性肾透明细胞癌进行了免疫组化染色,并进行文献复习。结果：本例右肾肿物18年。大体见肿物由多发不等的囊腔组成。镜下囊内壁主要由单层立方或柱状上皮被覆,部分为多层并有乳头形成。瘤细胞胞质透亮,无明显异型性。癌细胞免疫表型cytokeratin、CEA和vimentin呈阳性表达。本例诊断为多囊性肾透明细胞癌。结论：多囊性肾透明细胞癌是一种罕见的肾癌病理类型。临床上主要采用根治切除术。本瘤的生物学行为属于低度恶性肿瘤。     

透明细胞乳头状肾细胞癌1例

<正>患者女性,60岁,因右侧输尿管结石入院,自诉偶有右腰部酸胀感,无发热,无尿频、尿急、尿痛,无肉眼血尿;查体:心肺听诊无殊,腹软,未及包块,未及压痛、反跳痛,右肾区轻叩痛,左肾区无叩痛;腹部CT示右肾实质内见直径1. 6 cm等低密度结节影突出肾轮廓,增强后动脉期强化类似肾皮质,后期密度减低,呈相对略低密度,报告提示右肾占位,肾癌可能。行右肾部分切除术,送病理检查。     

转移性透明细胞性肾细胞癌42例临床病理分析

目的探讨转移性透明细胞性肾细胞癌(clear cell renal cell carcinoma,CCRCC)的临床病理学特征、诊断及鉴别诊断。方法回顾性分析42例转移性CCRCC的临床病理资料,并复习相关文献。结果 42例转移性CCRCC中,男性35例,女性7例;转移部位依次为肺19例,骨8例,淋巴结及软组织各3例,肾上腺、皮肤及脑各2例,肝、小肠及鼻腔各1例。42例转移性CCRCC中,31例于肾原发灶手术切除后3周~11年出现转移,4例原发灶与转移灶同时发现;28例转移灶为单发,14例为多发性。34例转移性CCRCC仍具有原发性CCRCC的组织学形态,4例出现多灶状坏死,6例呈肉瘤样分化。Fuhrman细胞核分级:Ⅰ级4例、Ⅱ级13例、Ⅲ级18例、Ⅳ级7例。17例间质小血管呈簇状增生。免疫组化标记42例转移性CCRCC中CD10、vimentin、CAⅨ、PAX8、RCC和EMA阳性例数分别为39例(92.9%)、40例(95.2%)、38例(90.5%)、38例(90.5%)、31例(73.8%)和38例(90.5%)。结论转移性CCRCC具有独特的临床病理学特征,结合临床病史及肿瘤组织形态学特点,联合免疫组化标记vimentin、EMA、CD10、CAⅨ、PAX8等有助于诊断及鉴别诊断。     

DNA 修复基因与肾透明细胞癌相关性的研究进展

肾细胞癌 (renal cell carcinoma, RCC) 深刻且广泛地影响全人类, 肾透明细胞癌 ( clear cell renal cell carcinoma, ccRCC) 是其最主要病理亚型。 在过去 30 年, 肾细胞癌的生物分子机制被不断挖掘, 随 着 DNA 修复途径及相关基因研究深入, 逐渐发现了他们之间的联系。 细胞总是暴露在各种损伤因素下, 导 致基因组损伤, 若 DNA 修复系统功能缺陷, 导致基因组不稳定, 最终细胞凋亡或转变为癌细胞。 DNA 修 复基因 (DNA repair gene, DRG) 与 ccRCC 在易感性, 预后及治疗方面具有显著的生物学相关性, 为进一 步探索 ccRCC 与 DNA 损伤修复之间的分子机制, 确定 ccRCC 新的分子标志物, 寻找合适免疫抑制物治疗 靶点奠定了一定的基础。     

转移性非透明细胞肾细胞癌的治疗进展

非透明细胞肾细胞癌(nccRCC)是一组异质性疾病,一旦出现转移,对传统的全身治疗耐药,预后差。近些年的研究表明血管内皮生长因子抑制剂、m TOR抑制剂、MET抑制剂、细胞毒药物和免疫节点抑制剂对nccRCC治疗有效。对这些治疗方法进行综述以期提高对每种亚型nccRCC的最优治疗策略的认识。     

双侧甲状腺转移性肾透明细胞癌1例

患者女性,56岁,因颈前无痛性肿物1个月入院。初诊:甲状腺双侧肿瘤。患者于7年前因肾癌行右肾癌切除术。查体:一般情况好,双侧甲状腺可触及一表面光滑,随吞咽上下移动的肿物;甲状腺功能正常。X线示气管向左移位。腹部(B超、彩色多普勒)超声示:甲状腺右叶内探及一4·7cm×3·2cm椭圆形低回声团块,边界清,规整,内部滋养层血管增多,血流丰富;左叶内探及一3·0cm×2·0cm的低回声区,边界欠规整,内部回声不均匀,血流较丰富呈“花环征”。SPECT示甲状腺位置正常,两叶明显肿大,形态不完整,双侧甲状腺示踪剂分布不均匀,右叶中下部见一较大示踪剂缺…     

甲状腺转移性透明细胞肾细胞癌1例

患者男性,50岁,3年前无意间触及颈部前侧有一花生粒大小肿物,无其他不适.患者于2019年11月至上海市松江区中心医院检查,颈部彩超示:甲状腺右叶结节,TI-RADS 4a类.甲状腺增强CT示甲状腺右叶、左叶占位,考虑腺瘤可能.临床考虑甲状腺肿瘤收入院,行右侧甲状腺切除术,手术切除标本送病理检查.后经仔细询问,患者曾于...     

肾透明细胞癌差异基因的生物信息学分析与验证

目的通过生物信息学(生信学)分析筛选肾透明细胞癌的潜在靶基因,验证并探讨其意义。方法运用生信学分析筛选基因芯片中肾透明细胞癌组织与正常肾组织间的差异基因,通过功能和通路富集分析和构建蛋白相互作用网络筛选核心基因;运用实时定量PCR、蛋白免疫印迹和免疫组织化学检测该基因在肾透明细胞癌组织和对应癌周正常肾组织中的表达水平;通过TCGA数据库分析该基因在肾透明细胞癌中的表达水平及其对生存预后的影响。结果生信学分析筛选出差异表达的核心基因GATA3,其在肾透明细胞癌组织中表达水平显著低于相对应的癌周正常肾组织(P0.01)。TCGA数据显示GATA3在肾透明细胞癌中的表达水平显著降低(P0.01),GATA3低表达的肾透明细胞癌患者的生存期显著降低(P0.05)。结论生信学分析的使用能有助于筛选靶基因并分析其功能,GATA3的差异性表达可能对解释肾透明细胞癌发生、发展机制有一定帮助,并且可能被用作肾透明细胞癌的新型诊断标志物或治疗靶点。     

蛋白质组学分析肾透明细胞癌中的乙酰化蛋白质

目的:为探究蛋白质乙酰化在肾透明细胞癌(ccRCC)中的角色,本研究采用乙酰化搜库策略,分析ccRCC临床组织样本的质谱数据,全面鉴定ccRCC相关的乙酰化蛋白、乙酰化位点及差异表达蛋白,并分析其所参与的信号通路,为寻找临床诊断的分子标志物及治疗靶点提供信息。方法:通过检索ProteomeXchange质谱数据库,筛选8对ccRCC和癌旁组织样本数据。通过不同的搜库策略鉴定分析差异表达蛋白及乙酰化蛋白,利用聚类分析、GO富集分析、KEGG通路分析等生物信息学手段对差异蛋白进行深入探讨,并应用Western blot技术对3对ccRCC及癌旁组织中的蛋白乙酰化水平进行验证。结果:本次质谱数据挖掘,总共鉴定到464个差异蛋白,其中上调蛋白104个,下调蛋白360个。通过GO富集和KEGG通路分析发现,上调蛋白主要参与了血管收缩、补体和凝血级联系统、血小板激活等过程。另外,我们鉴定到乙酰化蛋白503个,包含乙酰化位点1 397个,与癌旁组织相比,8组ccRCC组织中的蛋白乙酰化水平均显著下调。Western blot实验确证ccRCC组织中的乙酰化蛋白水平较癌旁组织显著减少。从乙酰化质谱鉴定...     

基于多字典学习框架的肾透明细胞癌预后分析模型

肾透明细胞癌是一种高度异质的肿瘤,具有复杂多变的临床表现.基于病理全切片图像的肾透明细胞癌自动预后分析,可辅助医生做出临床决策,从而达到更好的治疗目的.肾透明细胞癌的组织异构性使得针对预后分析任务的特征提取存在很大的挑战性.提出针对肾透明细胞癌病理全切片图像的多字典学习框架,自适应获取病理全切片图像的有效信息,进行肾透...     

Clinical Implications of HSC70 Expression in Clear Cell Renal Cell Carcinoma

Purpose: The role of heat shock protein 70 (HSC70) in the progression of clear cell renal cell carcinoma (ccRCC) is unclear. This study explored the effect of the HSC70 on the survival of ccRCC patients.Methods: Immunohistochemical analysis was performed to determine HSC70 expression in samples obtained from 121 ccRCC patients with at least 5 years of follow-up. We also analyzed the association between HSC70 expression and clinicopathological characteristics. Furthermore, the association of overall survival (OS) with HSC70 expression was analyzed using Kaplan-Meier curves. Finally, we used the Oncomine and CCLE databases to determine the effects of HSC70 mRNA expression on ccRCC.Results: HSC70 expression was associated with distant metastasis and death of ccRCC patients. HSC70 was expressed in the nucleus and/or cytoplasm of ccRCC cells. The incidence of distant organ metastasis and death was higher in patients with HSC70 expression than in those without it. Survival analysis revealed that patients with HSC70 expression had significantly shorter OS. Oncomine analyses also showed that the HSC70 mRNA was significantly upregulated in ccRCC tissues.Conclusions: HSC70 expression was related to adverse prognosis, and patients with HSC70 expression had a worse prognosis than those without HSC70 expression. HSC70 may thus serve as a potential therapeutic target for ccRCC.     

Insulin Receptor Expression in Clear Cell Renal Cell Carcinoma and Its Relation to Prognosis

Purpose

Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC).

Materials and Methods

Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival.

Results

IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn''t significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies.

Conclusion

IR expression in CCRCC may be associated with favorable prognostic factors.     

Immunophenotypes of Glycogen Rich Clear Cell Carcinoma

Purpose

Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported.

Materials and Methods

Here, we present three cases of GRCC and their immunohistochemical profiles.

Results

Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%).

Conclusion

In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.     

Glycogen-rich Clear Cell Carcinoma of the Urethra: An Ultrastructural Study

A 49-year-old black woman developed a urethral glycogen-rich clear cell carcinoma. She was treated with anterior pelvic exenteration. The resected lymph nodes, vagina, uterine cervix, endometrium, ovaries, and urinary bladder were free of neoplasm. Histologically the neoplasm consisted of clear cells growing in sheets and occasional papillary structures. In some areas, hobnail cells were present. Ultrastructurally, the cells had apical caps, short microvilli, and complex cell bases, and contained abundant glycogen. These features were identified in one, but not the other of two previously reported cases. Because glycogen-rich clear cell carcinomas of the lower urinary tract do not resemble ultrastructurally mesonephric remnants or carcinomas known to arise from them, these glycogen-rich clear cell carcinomas should not be called “me-sonephromas” as has been the practice.     

Glycogen-rich Clear Cell Carcinoma of the Urethra: An Ultrastructural Study

A 49-year-old black woman developed a urethral glycogen-rich clear cell carcinoma. She was treated with anterior pelvic exenteration. The resected lymph nodes, vagina, uterine cervix, endometrium, ovaries, and urinary bladder were free of neoplasm. Histologically the neoplasm consisted of clear cells growing in sheets and occasional papillary structures. In some areas, hobnail cells were present. Ultrastructurally, the cells had apical caps, short microvilli, and complex cell bases, and contained abundant glycogen. These features were identified in one, but not the other of two previously reported cases. Because glycogen-rich clear cell carcinomas of the lower urinary tract do not resemble ultrastructurally mesonephric remnants or carcinomas known to arise from them, these glycogen-rich clear cell carcinomas should not be called “me-sonephromas” as has been the practice.     

Glycogen-rich Clear Cell Carcinoma of the Breast An Autopsy Case

An autopsy case of glycogen-rich clear cell carcinoma (GRCCC) which arose in the right breast of a 72 year old woman is reported. Light microscopic examination of the small finger tip-sized tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Im-munohistochemically, most of the clear tumor cells were stained for epithelial membrane antigen (EMA) and alpha lactalbumin, whereas a few eosinophilic tumor cells were positive for S 100 protein, EMA and actin. Electron microscopically, aggregates of glycogen particles, numerous empty glycogen lakes, microvilli, tight junctions and basal lamina were identified. Autopsy disclosed marked metastases to the liver, lung, adrenal, skin and lymph nodes. Primary breast cancer was confirmed by exclusion of a primary at any other site. It is suggested that although rare, GRCCC of the breast is as aggressive as usual invasive ductal carcinoma, and is associated with severe nodal and blood borne metastases, followed by death. Acta Pathol Jpn 39: 469 472, 1989.