TTK与肾透明细胞癌的临床病理特征及患者预后的相关性分析

目的探讨TTK在肾透明细胞癌(ccRCC)组织中的表达水平及其与ccRCC患者临床病理特征和预后的相关性,并研究TTK在ccRCC进展中的潜在作用。方法对112例ccRCC标本及其对应的癌旁正常组织行免疫组织化学(IHC)测定,根据TTK表达水平将患者分为TTK高表达组和TTK低表达组。分析患者年龄、性别和分期等临床特征与TTK表达水平的相关性。分别通过集落形成实验和Transwell实验检测TTK对ccRCC细胞增殖和侵袭的影响,并通过动物实验观察TTK对肿瘤生长和转移的影响。结果 ccRCC患者标本中TTK表达水平明显升高。TTK表达水平与患者T分期(P=0.008)和淋巴结转移(P=0.023)明显相关。TTK敲除能够抑制ccRCC细胞株HTB-47和CRL-1932的增殖和侵袭能力,还有助于小鼠体内ccRCC的生长和转移。结论 TTK能够影响ccRCC的进展,并可能成为ccRCC治疗的新靶点。     

BCAN基因在肾透明细胞癌中的表达及临床意义

目的以基因表达数据集资料为研究对象,分析BCAN基因在肾透明细胞癌中的表达情况以及对患者预后的影响。方法在Oncomine数据库中挖掘BCAN在肾透明细胞癌(ccRCC)中的表达情况。从TCGA数据库中获取ccRCC患者临床资料和目的基因的表达信息并进行统计分析。利用GEO数据库中GSE73731数据集的ccRCC样本进行基因富集分析。利用String数据库分析与BCAN相关的蛋白。结果BCAN低表达组的ccRCC患者在病理分期及T分期方面低于高表达组(P<0.001;P=0.001);N分期及M分期差异无统计学意义(P>0.05)。BCAN低表达组患者的总生存期优于高表达组(P=0.033)。BCAN基因高表达组的样本主要富集在KRAS信号通路。结论BCAN可以通过多种途径来促进肿瘤细胞的侵袭能力,有望成为ccRCC不良预后的重要生物标志物之一。     

基于TCGA数据库分析BIRC5在肾透明细胞癌中的表达及预后

目的通过分析杆状病毒凋亡抑制蛋白5(BIRC5)在肾透明细胞癌(ccRCC)组织中的表达,阐明BIRC5对其早期诊断及作为预后预测因子的作用。方法利用GEO、TCGA数据库和HPA分析BIRC5在ccRCC组织中mRNA和蛋白质水平的变化。运用UALCAN和LinkedOmics数据库阐述BIRC5表达与ccRCC临床病理学参数的相关性及对预后的影响。采用GEPIA、Kaplan-Meier Plotter、SurvExpress分析BIRC5表达与ccRCC预后的关系。结果BIRC5 mRNA在ccRCC中高表达,并且与ccRCC患者TNM分期相关(P<0.05),与ccRCC进展高度相关,高表达BIRC5mRNA是ccRCC患者不良预后指标。免疫组织化学结果证实,与正常肾组织相比,ccRCC中BIRC5蛋白表达量显著升高。结论在ccRCC中,BIRC5高表达是一种重要的早期诊断及不良预后指标,有望成为ccRCC早期诊断和预后预测标志物。     

肾周脂肪平均密度对腹腔镜肾部分切除术的影响

目的:探讨肾周脂肪平均密度对腹腔镜肾部分切除术的影响。方法:回顾性分析2014年4月～2018年4月上海长征医院泌尿外科135例腹腔镜肾部分切除术患者。通过CT影像学资料对肾周脂肪平均密度进行计算,并将患者分为高密度组和低密度组,比较两组患者手术时间、BMI、术中出血、R.E.N.A.L、PAUDA评分及肾周脂肪平均密度等指标。结果:高密度组与低密度组手术时间比较差异有统计学意义(P0.05),两组患者在BMI、术中出血量、肾周脂肪厚度(PD)等方面比较差异无统计学意义。结论:本研究发现MAP肾周脂肪评分无法准确地评估肾周脂肪含量,而肾周脂肪平均密度可作为肾周脂肪的评估指标。     

单中心评估保留肾单位手术在cT1期Xp11.2易位型肾癌的可行性

目的 评估保留肾单位手术(NSS)在cT1期Xp11.2易位型肾癌(Xp11.2 tRCC的可行性。方法 回顾性对比分析2007年1月至2020年8月在南京鼓楼医院确诊的45例cT1期Xp11.2 tRCC和135例cT1期透明细胞肾细胞癌(ccRCC)临床病理资料。结果 在Xp11.2 tRCC中c T1a期和c T1b期患者各有13例(52%)和11例(55%)行NSS,而在ccRCC中cT1a期和cT1b期患者各有57例(74%)和48例(82.8%)行NSS。与ccRCC相比,Xp11.2 tRCC瘤体距离肾盂集合系统或肾窦脂肪较近,居于肾脏中央偏内生型生长(均P0.05)。生存分析显示cT1b期Xp11.2tRCC患者根治性肾切除术(RN)组无进展生存期(PFS)明显优于NSS组(P=0.036),而cT1a期和c T1期患者总体生存期(OS)和PFS差异均无统计学意义(P0.05)。然而多因素分析显示手术方式不是影响Xp11.2 tRCC患者疾病进展的独立危险因素(P=0.475和P=0.061)。结论 cT1a期Xp11.2 tRCC患者行NSS是安全可行的,而cT1b期患者应慎重选择NSS。     

肾透明细胞癌组织浸润CD8＋T细胞中异质性胞核核糖核蛋白A2B1的表达及其临床意义

目的探讨异质性胞核核糖核蛋白A2B1(HNRNPA2B1)在肾透明细胞癌(ccRCC)组织浸润CD8+T细胞中表达分布特征及其临床意义。方法利用基因表达综合数据库(GEO)公共数据分析HNRNPA2B1在ccRCC组织浸润免疫细胞以及CD8+T细胞亚群中的表达分布;转录组测序技术(RNA-seq)差异分析高、低表达HNRNPA2B1 ccRCC患者高变免疫基因并富集相关通路。多标记免疫荧光染色(mIHC)检测223例ccRCC患者癌组织和癌旁正常组织浸润CD8+T细胞中HNRNPA2B1的表达分布特征, 采用R语言做统计分析, 经单因素Cox、最优子集回归和LASSO回归交叉验证筛选临床因素并纳入多因素Cox回归构建列线图预测模型。Wilcoxon检验用于组间差异显著性分析, 生存分析采用Kaplan-Meier法和Log-rank检验。结果 HNRNPA2B1在CD8+T细胞上高表达并参与抗原加工呈递、T细胞增殖调节等多个信号通路。肾透明细胞癌患者肿瘤组织浸润HNRNPA2B1+CD8+T细胞比率高于癌旁正常组织[1.26%(0%, 35.56%)比0.28%(0%, 13.35%)...     

控制营养状态评分和相关炎性指标在肾透明细胞癌预后预测中的价值：一项多中心回顾性研究

目的 探讨控制营养状态(CONUT)评分和相关炎性指标在肾透明细胞癌(ccRCC)患者预后预测中的价值,为临床更好地评估病情及制定个体化治疗方案提供参考。方法 回顾性分析2010—2018年宜宾市4所综合性医院收治的132例ccRCC患者的病历资料和生存情况,采用受试者工作特征曲线(ROC)分析CONUT评分及炎性指标中性粒细胞和淋巴细胞比值(NLR)、血小板和淋巴细胞比值(PLR)以及淋巴细胞和单核细胞比值(LMR)预测患者预后的曲线下面积和最佳截断值,Kaplan-Meier法绘制生存曲线,采用Log-rank检验和Cox回归分析影响预后的因素。结果 患者中位随访时间62(53,71)个月,随访期内死亡37例(28.03%),疾病特异性生存期(DSS)和无进展生存时间(PFS)分别为51(41,58)个月和46(35,56)个月,患者3、5年DSS分别为84.09%和71.97%,3、5年PFS分别为75.00%和71.97%。CONUT评分、NLR、PLR以及LMR预测患者预后的ROC曲线下面积(AUC)分别为0.980、0.905、0.899和0.884,最佳截断值分别为3.5...     

基于铜死亡相关基因的肾透明细胞癌中预后模型的构建与应用

目的:研究铜死亡相关基因(cuproposis-related genes, CRGs)在肾透明细胞癌(clear cell renal cell carcinoma, ccRCC)中的表达情况，构建预后模型并探讨其临床意义。方法:从TCGA数据库中获得522例ccRCC患者的转录组数据和临床病理数据。将患者随机分为训练集(262例)和验证集1(260例),并将总体患者作为验证集2(522例)。在训练集中采用差异性分析确定肿瘤组织和癌旁组织差异性表达的CRGs,使用LASSO-Cox回归分析构建ccRCC的CRGs预后模型(OSCRG)。根据OSCRG将患者分为低危组和高危组，使用Kaplan-Meier生存分析研究OSCRG与总体生存期(overall survival, OS)的关系。使用单因素和多因素Cox回归分析构建包含OSCRG和临床病理参数的列线图预测OS,并在验证集中验证该列线图的准确性。最后使用KEGG和GO基因富集分析探索差异性表达的CRGs的生物学功能。结果:在训练集中有9个差异性表达的CRGs,并且均与OS相关。LASSO-Cox回归分析确定了3个CRGs并构建O...     

术前红细胞分布宽度对根治性膀胱切除患者预后的临床意义

目的研究术前外周血红细胞分布宽度(RDW)在根治性膀胱切除术患者预后中的临床意义。方法本研究对2009年1月至2018年11月期间共210例接受根治性膀胱切除术的患者进行了回顾性分析。采用X-tile软件来确定RDW的最佳临界值;采用Kaplan-Meier法来评估RDW对患者总生存期(OS)和无疾病进展期(PFS)的影响;采用卡方检验来比较两组患者的临床基线特征;采用Cox回归模型来分析影响根治性膀胱切除术患者预后的独立危险因素。结果 RDW的最佳临界值是14.2;Kaplan-Meier法分析表明,术前高RDW组(14.2)的膀胱癌患者与OS(Log-rank=6.703,P0.05)和PFS(Log-rank=4.821,P0.05)降低显著相关;低RDW组和高RDW组的患者在T分期上差异有统计学意义(χ2=11.254,P=0.010);Cox多因素分析证实术前RDW是接受根治性膀胱切除术患者OS和PFS的预测因素。结论高RDW可以作为接受根治性膀胱切除术患者OS和PFS不良的危险因素。     

无远处转移肾癌伴肾静脉瘤栓的长期疗效和预测影响因素北大核心CSCD

目的探讨无远处转移肾癌伴肾静脉瘤栓患者行开腹根治性肾切除联合瘤栓取出术的预后影响因素。方法回顾性分析2000年1月~2014年9月我院113例术后病理证实为肾癌伴肾静脉瘤栓的临床资料,均为Mayo 0级瘤栓,采用Kaplan-Meier生存分析,Cox比例风险模型评价肾癌伴肾静脉瘤栓的预后。结果 106例获得随访,随访率93.8%（106/113）,中位随访时间61个月（12~186个月）,36例死亡,中位生存127个月（5~186个月）,5年肿瘤特异性生存率（cancer-specific survival,CSS）为61.3%,10年CSS为50.4%。Cox比例风险模型结果显示副瘤综合征（β=2.457,P=0.000）、Fuhrman分级（G3/4）（β=2.617,P=0.000）和肾周脂肪受累（β=1.369,P=0.002）是肾癌伴肾静脉瘤栓患者的独立预后因素,同时伴有3项危险因素的患者中位生存仅14个月。结论术前无远处转移的肾癌伴肾静脉瘤栓患者行开腹根治性肾切除联合瘤栓取出术后预后良好,伴有副瘤综合征,高Fuhrman分级和肾周脂肪受累的患者预后差。     

High perirenal fat thickness predicts a poor progression-free survival in patients with localized clear cell renal cell carcinoma

Objectives

The aim of the study was to assess the association between the progression-free survival (PFS) and perirenal fat thickness (PFT) in a population of histopathologically confirmed, localized clear cell renal cell carcinoma (ccRCC) patients.

The prognostic value of the site of invasion in T3aN0M0 clear cell renal cell carcinoma

Background

The 7th Tumor-Node-Metastasis system for clear cell renal cell carcinoma (ccRCC) classified renal sinus fat invasion (SFI), perirenal fat invasion (PFI), or renal vein invasion (RVI) as stage pT3a. However, their close interactions and prognostic value of them remain controversial. The goal of this study is to further analyze their prognostic values for patients with T3aN0M0 ccRCC.

肿瘤细胞性染色体数目异常在肾透明细胞癌中的生物学作用及其与SSIGN评分的关系

目的探讨肿瘤细胞性染色体数目异常在肾透明细胞癌中的生物学作用及其与SSIGN评分的联系。方法收集20例男性肾透明细胞癌患者,根据SSIGN评分分为高SSIGN评分组和低SSIGN评分组,并选择5例非肿瘤肾组织作为阴性对照。采用荧光原位杂交技术分别检测标本X、Y染色体数目的异常率,观察比较高SSIGN评分组与低SSIGN评分组以及正常组之间的性染色体异常率的差异。结果 5例非肿瘤肾组织无异常,与肿瘤组比较,有显著性差异(P0.05)。高SSIGN评分组比低SSIGN评分组的X染色体获得率没有显著的变化,无统计学意义(P0.05),而高SSIGN评分组比低SSIGN评分组的Y染色体获得率有明显增高,差异有统计学意义(P0.05)。结论肾透明细胞癌肿瘤细胞存在性染色体的异常,而非肿瘤肾组织无异常率的发现,提示性染色体异常与肾透明细胞癌的发生发展有着密切的关系。肾透明细胞癌高SSIGN评分组比低SSIGN评分组的Y染色体获得率有明显增高,Y染色体获得很可能是肾透明细胞癌预后差的特征性改变,可望作为判断肾透明细胞癌恶性程度和预后的指标之一。     

Impact of several histopathological prognosticators and local tumour extension on oncological outcome in pT3b/c N0M0 renal cell carcinoma

OBJECTIVE

To investigate the prognostic relevance of different histopathological features and local tumour extension in patients with pT3b/c N0M0 renal cell carcinoma (RCC), as recently new proposals of reclassifying tumour fat invasion in pT3b/c RCC have been made but the effect of other histopathological tumour characteristics and combinations thereof with tumour invasion has yet to be determined in these patients.

PATIENTS AND METHODS

Between 1990 and 2006, 1943 patients underwent surgical treatment for renal tumours in our institution, of which 175 patients (8.7%) had pT3b/c RCC. After exclusion of 57 patients (32.6%) with lymph node and/or distant metastases at the time of diagnosis, 118 (67.4%) remained for retrospective analysis. Different histopathological features and local tumour extension were studied for their association with cancer‐specific‐survival (CSS) and progression‐free‐survival (PFS) by univariate and multivariate analyses. Histopathology was reviewed and revised according to the 2002 Tumour‐Nodes‐Metastasis (TNM) classification system by one pathologist (S.B.). CSS and PFS were estimated by the Kaplan–Meier method.

RESULTS

Follow‐up data were obtained from 110 patients at a median (range) of 3.2 (0.3–16.1) years. In univariate analysis, microvascular invasion (MVI) and capsular invasion increased the risk of tumour progression by 2.05‐ and 2.72‐times (P = 0.037 and P < 0.001). Overall, tumour fat invasion (TFI) and the presence of areas composed by cells with eosinophilic cytoplasm were associated with a higher risk of progression (P = 0.001 and P = 0.011) and reduced CSS (P = 0.037 and P = 0.017). In multivariate analysis, MVI and capsular invasion were associated with a two‐fold increased risk of dying from cancer (hazard risk ratio, HR 2.22, P = 0.045 and HR 2.31, P = 0.011). TFI in general (P = 0.004) and specifically coexistent perirenal fat invasion (PFI) and renal sinus fat invasion (RSFI) were associated with a three‐fold increased risk of developing tumour progression (HR 3.36, P = 0.001). The 10‐year CSS and PFS rates were 39% and 36% for all patients, 47% and 45% for pT3b/c RCC with no PFI or RSFI, and 25% and 10% for PFI + RSFI.

CONCLUSION

Patients with pT3b/c RCC with MVI, capsular invasion, TFI and especially PFI + RSFI, have a markedly reduced prognosis compared with patients with pT3b/c RCC without these features. When these results are corroborated by additional studies and external validation, modification of the TNM classification system would be a sensible consequence.     

Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma

Objective

To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC).

The impact of family history on pathological and clinical outcomes in non‐syndromic clear cell renal cell carcinoma

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To investigate the impact of family history on pathological and clinical outcomes after surgery for clear‐cell renal cell carcinoma (ccRCC) in patients with non‐syndromic disease.

PATIENTS AND METHODS

We reviewed 2677 patients treated with radical nephrectomy or nephron‐sparing surgery for non‐cystic ccRCC between 1970 and 2004 to identify patients with a family history of ccRCC. Patients with von Hippel–Lindau, tuberous sclerosis, or Birt–Hogg–Dube syndrome were excluded from analysis. Demographics and clinico‐pathological outcomes were compared to patients with ccRCC without a family history of kidney cancer using chi‐squared and Fisher’s exact tests. Postoperative cancer‐specific survival was estimated using the Kaplan–Meier method.

RESULTS

We identified 42 patients (1.6%) with a family history of ccRCC who were treated for non‐cystic ccRCC, with a median follow‐up of 4.7 years (range 1–34). Demographics and tumour characteristics, including tumour stage and grade, were similar between the two groups. Patients with a family history of ccRCC were more likely to have bilateral tumours (11.9 vs 2.2%, P= 0.003). Nevertheless, cancer‐specific survival rates for patients with and without a family history of ccRCC were similar at 5 years (75.7 vs 71.1%) and 10 years (53.9 vs 62.2%).

CONCLUSIONS

Patients with a family history of ccRCC have pathological and clinical outcomes similar to patients with sporadic ccRCC. The increased incidence of bilateral tumours associated with a family history of ccRCC provides further evidence to support a nephron‐sparing surgical approach when feasible.     

SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75–80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined.MethodsOur current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01).ResultsThe results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044).ConclusionsA further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.     

Prognostic significance of tumor grade for renal cell carcinoma

BACKGROUND: The natural history and prognosis of renal cell carcinoma cannot be predicted. Based on the Japanese classification system, the value of nuclear grade were assessed as a possible prognostic factor for renal cell carcinomas. METHODS: In this retrospective study of 116 patients with renal cell carcinoma, radical nephrectomy was performed. Survival rates were calculated using the Kaplan-Meier method and multivariate analysis was performed using Cox's proportional hazard model. RESULTS: Distribution by stage and grade in the population of renal cell carcinomas was as follows: pT1 in 13 cases (11.3%), pT2 in 65 cases (56.5%), pT3 in 36 cases (31.3%) and pT4 in one case (0.9%) and grade 1, 28 (24.1%), grade 2, 69 (59.5%) and grade 3, 16 (13.8%). Three cases could not be determined because of pre-operative embolization of the renal cell carcinomas. Nuclear grade was correlated with stage (P=0.0002), the presence of perirenal fat involvement (P=0.003) and metastases (P=0.007). A significant difference in survival was found between grades 1 and 3 (P=0.0001) and grades 2 and 3 (P=0.0001), respectively. Survival was significantly correlated with sex (P=0.0125), tumor size (P=0.0001), the presence of lymph node metastasis (P=0.0001), renal vein involvement (P=0.0001), perirenal fat involvement (P=0.002) or distant metastasis (P=0.0001). The multivariate analysis showed that the occurrence of tumor grade (P=0.0006) or distant metastasis were independent prognostic values. CONCLUSION: The observations lead us to conclude that the nuclear grade according to the Japanese classification system appears to be of reliable prognostic value for renal cell carcinomas.     

5t4在肾透明细胞癌中的表达及意义

目的探讨滋养层糖蛋白5t4在肾透明细胞癌中的表达及其意义。方法采用免疫组织化学技术检测72例肾透明细胞癌组织标本、17例癌旁肾组织以及14例非癌因素的肾脏组织标本中5t4的表达,并对5t4在肾透明细胞癌的表达与组织学分级的关系进行分析。结果 5t4在肾细胞癌组织中的阳性率为70.8%,癌旁肾组织中的阳性率为41.2%,两者具有差异性(P0.05)。5t4在肾癌组织学分级中低分级与高分级的表达存在显著差异(P0.01)。结论 5t4可作为判断肾透明细胞癌分化程度的标志物。