Prognostic significance of tumor multifocality on outcomes in patients with upper tract urothelial carcinoma after radical nephroureterectomy: A cohort study

To identify the prognostic impact of tumor multifocality on upper tract urothelial carcinoma (UTUC) outcomes in patients treated with radical nephroureterectomy (RNU). Study included 342 consecutive patients with UTUC. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Tumor multifocality was significantly associated with a history of previous non-muscle invasive bladder cancer (P < 0.001), tumor size (P < 0.001), gender (P = 0.009), tumor location (P = 0.005), and anemia (P = 0.01). The Kaplan–Meier method showed that tumor multifocality was significantly associated with worse recurrence-free survival (P < 0.001, log rank). Using multivariate analysis, tumor multifocality (HR, 2.86; 95% CI, 2.06 – 3.99; P < 0.001) was independently associated with recurrence free survival. During the follow-up, a total of 128 (37.4%) patients died, including 92 (28.2%) from UTUC. However, tumor multifocality was not associated with CSS (HR, 1.29; 95% CI, 0.89 – 1.96; P = 0.21) in univariate Cox regression analyses. Tumor stage (HR, 11.1; 95% CI, 3.64 – 33.8; P < 0.001), lymph node status (HR, 2.04, 95% CI, 1.05 – 3.94; P = 0.03) and preoperative anemia (HR, 3.50, 95% CI, 2.02 – 6.08; P < 0.001) were the only independent predictors associated with worse cancer-specific survival. Tumor multifocality is an independent prognostic factor of disease recurrence in patients treated with RNU for UTUC. Tumor multifocality is unable to predict cancer specific survival in a single-center series of consecutive patients who were treated with RNU.     

CIP2A在膀胱尿路上皮癌组织中的表达及其临床意义

目的 研究蛋白磷酸酶2A癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在膀胱尿路上皮癌组织中的表达及其与临床病理特征的关系,探讨其成为膀胱尿路上皮癌预后指标的可行性.方法 应用RT-PCR和Western blot检测CIP2A mRNA和蛋白在25例膀胱尿路上皮癌和对应癌旁组织中的表达情况;应用组织芯片技术和免疫组织化学方法,检测CIP2A在117例膀胱尿路上皮癌和30例癌旁组织中的表达情况,分析CIP2A与膀胱尿路上皮癌患者临床病理特征及预后之间的关系.结果 CIP2A mRNA和蛋白在25例配对膀胱尿路上皮癌组织中的表达水平明显高于癌旁组织.免疫组织化学检测发现,膀胱尿路上皮癌组织中CIP2A蛋白的阳性表达率为76.9％(90/117),明显高于癌旁组织的6.7％ (2/30),差异有统计学意义(P＜0.001).CIP2A表达与肿瘤病理分级(P＜0.001)、临床分期(P＜0.001)、肿瘤大小(P=0.002)和淋巴结转移(P=0.046)有关,但与年龄、性别及肿瘤数目无关(P＞0.05).KaplanMeier单因素分析显示,CIP2A蛋白高表达是总体生存率和无复发生存率的影响因素(P＜0.001).Cox多因素风险比例模型显示,与总生存率相关的独立预后因素为临床分期、肿瘤病理分级和CIP2A表达,与无复发生存率相关的独立预后因素亦为临床分期、肿瘤病理分级和CIP2A表达.结论 CIP2A蛋白在膀胱尿路上皮癌组织中高表达,可能与膀胱尿路上皮癌的进展有关,其表达状态是膀胱尿路上皮癌患者独立预后因素.     

Association of perioperative blood transfusion with oncologic outcomes after radical nephroureterectomy for upper tract urothelial carcinoma

BackgroundTo test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).MethodsRetrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality.ResultsA total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92–1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89–1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93–1.28, p = 0.29).ConclusionsIn patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses.     

MEK5在膀胱尿路上皮癌组织中的表达及预后相关性分析北大核心

目的:探究膀胱尿路上皮癌组织中丝裂原活化蛋白激酶5(mitogen-activated protein kinase 5,MEK5)表达水平及其与预后相关性。方法:选取2015年06月至2017年06月本院收治的膀胱尿路上皮癌患者93例作为研究对象,术中收集入组患者癌组织及癌旁组织。采用qRT-PCR法、免疫组化染色法检测膀胱尿路上皮癌组织及癌旁组织中MEK5表达;Kaplan-Meier法绘制生存曲线分析膀胱尿路上皮癌组织中MEK5表达与患者预后相关性;Cox比例风险回归模型分析影响膀胱尿路上皮癌患者不良预后发生的危险因素;受试者工作特征(ROC)曲线分析膀胱尿路上皮癌组织中MEK5 mRNA对患者预后不良预测价值。结果:膀胱尿路上皮癌组织中MEK5 mRNA表达水平及MEK5蛋白阳性率明显高于癌旁组织(P<0.05)。高级别、T_(2)-T_(4) TNM分期、浸润性及淋巴结转移膀胱尿路上皮癌患者癌组织中MEK5蛋白高表达率明显高于低级别、T_(a)-T_(1) TNM分期、非浸润性及无淋巴结转移患者(P<0.05)。MEK5蛋白高表达患者中无复发生存16例,无复发生存率为31.37%;MEK5蛋白低表达患者中无复发生存28例,无复发生存率为66.67%,两组比较差异有统计学意义(P<0.05)。浸润性、低级别、T_(2)-T_(4) TNM分期、淋巴结转移、MEK5高表达是影响膀胱尿路上皮癌患者不良预后发生的独立危险因素(P<0.05)。结论:膀胱尿路上皮癌组织中MEK5呈高表达,与患者TNM分期、病理分型、病理分级、淋巴结转移等密切相关,可能作为临床评估患者预后的参考指标。     

Villin 1 is a predictive factor for the recurrence of high serum alpha-fetoprotein-associated hepatocellular carcinoma after hepatectomy

The prognostic assessment of patients with hepatocellular carcinoma (HCC) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha-fetoprotein (AFP), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose mRNA expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum AFP-associated HCC patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum AFP-associated HCC tumor tissues. In the present analysis, only VIL1 was significantly correlated with the recurrence of HCC. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of VIL1 mRNA was also correlated with high serum PIVKAII, vascular invasion (P < 0.05), poor differentiation, an advanced cancer stage (P < 0.01) and recurrence-free survival (P = 0.017). The upregulation of VIL1 mRNA was observed more frequently in the early recurrence patients as compared to the late recurrence patients. Cox regression univariate and multivariate analyses indicated that high serum AFP levels (overall survival, HR 1.675, P = 0.002; FRS, HR 1.359, P = 0.039) and Vil1 protein expression (overall survival, HR 0.253, P = 0.009; FRS, HR 0.401, P = 0.041) were independent, unfavorable prognostic factors for overall and recurrence-free survival of patients. We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC.     

金属硫样蛋白5在乳腺癌组织中的表达及其与预后的关系

目的探讨金属硫样蛋白5(MTL5)在乳腺癌组织中的表达与患者预后的关系。 方法本回顾性研究采用在中国人类遗传资源共享服务平台(编号：2005DKA2130)获得的2005年1月至2012年9月初次手术、术前无肿瘤远处转、未经过新辅助治疗的77例乳腺癌患者的癌组织和癌旁组织标本进行免疫组织化学实验。术后随访截止至2016年1月，随访时间为3.3～11.0年。用χ²检验、Fisher精确概率法及非参数检验分析MTL5在乳腺癌组织中表达与临床病理特征的关系；用Cox比例风险回归模型分析MTL5表达对患者复发和死亡风险的影响；用Kaplan-Meier法进行生存分析并绘制生存曲线；采用log-rank检验比较不同MTL5表达患者的OS率和无复发生存率。 结果在纳入的77例成对样本中，排除脱片样本5例、癌组织和癌旁组织均无MTL5表达的样本29例、MTL5均有表达但差别无法判断的样本2例后，剩余41例，其中MTL5高表达(癌组织中MTL5表达高于癌旁组织)者21例，低表达(癌组织中MTL5表达低于癌旁组织)者20例。MTL5表达与年龄、腋窝淋巴结转移相关(P＝0.021；Z＝－2.281，P＝0.023)，而与ER、PR、肿瘤大小、病理类型、HER-2无关(χ²＝0.034，P＝0.853；χ²＝0.042，P＝0.837；χ²＝1.177，P＝0.278；P＝0.663；P＝1.000)。单因素分析显示：腋窝淋巴结转移及MTL5表达为复发和死亡风险因素(复发风险：N₃期与N₀期比较，HR＝14.524，90%CI: 2.322～90.858，P＝0.004；MTL5高表达者比低表达者，HR＝8.752, 90%CI: 1.093～70.054，P＝0.041；死亡风险：N₃期与N₀期比较，HR＝8.469，90%CI: 1.495～47.988，P＝0.016；MTL5高表达者比低表达者，HR＝8.255, 90%CI: 1.031～66.081，P＝0.047)。多因素分析显示：高表达MTL5的乳腺癌患者复发风险更高，且可以作为独立风险因素(HR＝11.320, 95%CI：1.022～125.436，P＝0.048)；同样，高表达MTL5的乳腺癌患者有更高的死亡风险，且可以作为独立风险因素(HR＝9.191, 95%CI：1.037～81.430，P＝0.046)。MTL5高表达者OS率及无复发生存率均低于MTL5低表达者(χ²＝5.652、6.084，P＝0.017、0.014)。 结论MTL5在乳腺癌组织中高表达可提示患者预后差，有潜力作为乳腺癌的治疗靶点。     

Survival Effect of Chemotherapy in Metastatic Upper Urinary Tract Urothelial Carcinoma

Background

Few data examined the potential survival benefit of chemotherapy (CHT) in the setting of metastatic upper urinary tract urothelial carcinoma (mUTUC). We hypothesized that a survival benefit might be associated with the use of CHT in nonsurgically treated primary mUTUC and tested this hypothesis within a large population-based cohort.

Effects of Variant Histology on the Oncologic Outcomes of Patients With Upper Urinary Tract Carcinoma After Radical Nephroureterectomy: A Propensity Score–Matched Analysis

PurposeTo determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU).Patients and MethodsThe data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes.ResultsUTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P = .011, P = .002, P = .006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR) = 1.92; 95% confidence interval (CI), 1.27-2.89; P = .002], CSS (HR = 4.47; 95% CI, 1.99-10.1; P = .001), and OS (HR = 3.00; 95% CI, 1.55-5.78; P = .001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P = .562, P = .060, P = .153, respectively).ConclusionUTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients.     

Robot-assisted versus open radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: A retrospective cohort study across ten years

PurposeRadical nephroureterectomy is the gold standard of treatment for high-risk non-metastatic urothelial carcinoma of the upper urinary tract. However, the optimal surgical approach remains a controversial debate. This study compared the perioperative and oncological outcomes of open and robot-assisted radical nephroureterectomies.Methods131 consecutive radical nephroureterectomies (66 robot-assisted nephroureterectomies vs. 65 open nephroureterectomies) for urothelial carcinoma of the upper urinary tract at a single tertiary referral center were included from 2009 to 2019. The perioperative and oncological outcomes were compared between both surgical approaches, including logistic regression analysis, propensity score matching, Kaplan Meier analyses, and Cox regression models.ResultsOverall, robot-assisted surgery had less blood loss (150 ml vs. 250, p = 0.004) and less positive surgical margins (1.5% vs. 15.4%, p = 0.004) at a comparable operating time (robotic 188min vs. 178). Any grade complications were more frequent after open surgery (40.9% vs. 63.1%, p = 0.011), and the length of stay was shorter after robotic nephroureterectomy (9 days vs. 12, p < 0.001). These differences remained significant in the propensity score matched analysis, except for the complication rates, which were still lower for the robotic approach, but no longer significant. At a median follow-up of 30.9 months (range 1.4–129.5), neither the progression-free survival (PFS, 2-year: robotic 66.7% vs. open 55.3%), nor the overall survival differed significantly (OS, 2-year: robotic 76.2% vs. open 68.4%). In the Cox regression, the surgical approach did not impact the PFS or OS. Lymph node metastases (HR 3.32, p = 0.008) had the strongest impact on the PFS besides patient age (HR 1.51 per 10 years, p = 0.025) and prior cystectomy (HR 2.42, p = 0.026) in the multivariate analysis.ConclusionsRobot-assisted radical nephroureterectomy had significant perioperative advantages at comparable oncological outcomes compared to open surgery for the treatment of urothelial carcinoma of the upper urinary tract at a high volume center, experienced in robotic surgery.     

β1、β2肾上腺素能受体在口腔鳞状细胞癌组织中的表达及其临床意义

目的 探讨β1肾上腺素能受体（β1 adrenergic receptors，β1-AR）和β2肾上腺素能受体（β2 adrenergic receptors，β2-AR）在口腔鳞状细胞癌组织中的表达及其临床意义。方法 收集2017年7月至2018年7月在广西医科大学附属口腔医院口腔颌面外科手术切除的口腔鳞癌组织及相应癌旁组织60例，并收集同期于本院就诊的15例非口腔鳞癌患者的口腔正常黏膜上皮组织。采用RT-qPCR及Western blot法检测β1-AR和β2-AR mRNA及蛋白在组织中的表达，采用Cox回归分析其与临床病理特征及预后的关系。结果 β1-AR、β2-AR蛋白及β2-AR mRNA在口腔鳞状细胞癌组织中的相对表达量均高于癌旁组织（P＜0.01）及正常口腔上皮组织（P＜0.05）。β1-AR、β2-AR mRNA和蛋白表达水平均与临床分期有关，其中β2-AR表达水平还与淋巴结转移及术后复发有关（均P<0.05）。β2-AR高表达组患者1 年、3 年总生存率及无进展生存率低于β2-AR低表达组（χ2=3.945，P=0.047；χ2=9.286，P=0.002），β1-AR表达水平与患者总生存期、无进展生存期无关。校正潜在的混杂因素后，多因素Cox回归显示β2-AR蛋白低表达是影响总生存期的保护因素（HR=0.149，95%CI：0.028~0.785，P=0.025）。结论 β1-AR、β2-AR在口腔鳞状细胞癌组织中高表达，β2-AR高表达患者预后较差，可能是口腔鳞状细胞癌潜在的预后评估指标。     

The relationship between patient physiology and cancer-specific survival following curative resection of colorectal cancer

The impact of patient physiology on cancer-specific survival is poorly documented. Patient physiology predicted overall, cancer-specific (Physiology Score>30; HR 8.64 (95% CI 3.00-24.92); P=0.0005) and recurrence-free survival (Physiology Score >30; HR 7.44 (95% CI 1.99-27.73); P=0.003) independent of Dukes stage following potentially curative surgery for colorectal cancer. This independent negative association with survival is a novel observation.     

二甲双胍对2型糖尿病合并前列腺癌患者生存率及无复发率影响的Meta分析

目的:系统评价二甲双胍对2型糖尿病并发前列腺癌患者生存结果的影响。方法:通过检索Pubmed、Embase和Cochrane这三个数据库。按照纳入、排除标准，由2名作者进行文献筛选、文献质量评估及数据提取，使用Review Manager 5.3软件对总体生存期（overall-survival,OS）、癌症相关生存期（cancer-specific survival,CSS）、无复发生存期（recurrence-free survival,RFS）进行分析，并把风险比（HR）作为效应量，各效应量以95%可信区间（confidence Interval，CI）表示。结果:共纳入22篇文献，共389 584例患者。Meta分析显示:与未使用二甲双胍治疗相比，使用二甲双胍能够明显提高前列腺癌患者OS（HR=0.74，95%CI:0.61～0.90,P=0.003）、CSS（HR=0.74，95%CI:0.62～0.87,P=0.000 3）及RFS（HR=0.72，95%CI:0.57～0.92，P=0.008）。结论:相比非二甲双胍治疗组，接受二甲双胍治疗的前列腺癌合并2型糖尿病患者，能够获得更好的总体生存期、癌症相关生存期以及无复发生存期。     

二甲双胍对胃癌合并2型糖尿病患者预后影响的Meta分析

目的:系统评价二甲双胍对胃癌合并2型糖尿病患者预后的影响。方法:计算机检索Pubmed、Cochrane library、Embase、知网、万方、维普等数据库,由两名研究员根据纳入、排除标准分别对检索文献进行筛选、质量评价及数据提取。使用RevMan5.4软件对总体生存率、癌症特异性生存率、无复发生存率进行Meta分析,效应量为风险比（hazard ratio,HR）,各效应量以95%置信区间（confidence interval,CI） 表示。结果:总共纳入10项研究,共计2 522例患者。Meta分析的结果显示,与未使用二甲双胍的患者相比,二甲双胍的使用能够提高胃癌合并2型糖尿病患者的总生存期（HR=0.71,95%CI:0.63~0.80,P＜0.000 01）、癌症特异性生存期（HR=0.76,95%CI:0.65~0.90,P=0.001）及无复发生存期（HR=0.58,95%CI:0.47~0.72,P＜0.000 01）。结论:与非二甲双胍治疗相比,接受二甲双胍治疗的胃癌合并2型糖尿病患者能够改善预后,总生存期、癌症特异性生存期及无复发生存期得到延长。     

Preoperative Neutrophil-Lymphocyte Ratio as an Independent Prognostic Marker for Patients With Upper Urinary Tract Urothelial Carcinoma

BackgroundTo predict the prognosis, we evaluated the significance of the preoperative neutrophil-lymphocyte ratio (NLR) in patients with upper urinary tract urothelial carcinoma (UUTUC).Patients and MethodsA cohort of 137 patients diagnosed with UUTUC from 1994 to 2008 at Tokyo Metropolitan Tama Medical Center was enrolled in this retrospective study. Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses.ResultsOn univariate analysis, pathologic T stage, grade, lymphovascular invasion, C-reactive protein (CRP) level, and NLR were significantly associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). The RFS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 74.3% and 30.4%, respectively. The CSS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 81.3% and 29.4%, respectively. The multivariate Cox proportional hazards regression models showed that the NLR could be an independent predictor for RFS and CSS. Based on the results of multivariate analysis, the scoring model was developed. RFS and CSS rates at 5 years were as follows: 0 risk factor, 97.1% and 97.0%, respectively; 1 risk factor, 91.1% and 90.9%, respectively; 2 risk factors, 39.5% and 58.6%, respectively; 3 risk factors, 26.6% and 28.6%, respectively; and 4 risk factors, 6.0% and 5.6%, respectively.ConclusionsThe preoperative NLR is an independent prognostic predictor. The model based on the NLR and pathologic factors can be useful in clinical practice.     

术前PNI、SII、SIM和白蛋白对牙龈癌患者术后生存的预测价值

目的:探讨术前预后营养指数(prognostic nutritional index,PNI)、炎症指数(system inflammation index,SII)、系统炎性标志物(systemic inflammatory marker,SIM)和白蛋白与牙龈癌患者预后的关系。方法:回顾性分析2014年12月至2017年11月在我院首次接受根治性手术切除的200例牙龈癌患者的临床和随访资料。通过受试者工作特征(receiver operating characteristic curve,ROC)曲线确定PNI、SII、SIM和白蛋白预测牙龈癌预后的最佳临界值。采用χ2检验分析术前PNI、SII、SIM和白蛋白与临床特征的关系。采用Kaplan-Meier法和Cox回归模型对牙龈癌患者预后影响因素进行单因素和多因素分析。结果:通过ROC曲线确定PNI、SII和SIM和白蛋白预测生存的最佳临界点分别为46.03、478.37、1.02和40.5 g/L。Cox多因素分析提示较晚的TNM分期(HR 2.873;95% CI 1.598~5.166;P＜0.000 1)、较低的PNI值(HR 0.414;95% CI 0.223~0.770;P=0.005)、较高的SIM值(HR 2.391;95% CI 1.329~4.299;P=0.004)以及低水平的白蛋白(HR 0.425;95% CI 0.203~0.888;P=0.023)是牙龈癌患者术后3年总生存期的独立危险因素,而较晚的TNM分期(HR 3.324;95% CI 2.055~5.089;P＜0.000 1)和低PNI值(HR 0.457;95% CI 0.296~0.705; P＜0.000 1)是术后3年无复发生存期(recurrence-free survival,RFS)的独立危险因素。结论:仅低水平的PNI是影响牙龈癌患者3年总生存期和3年无复发生存期的独立危险因素,对患者个体化治疗和随访具有指导意义。     

High Cytoplasmic Expression of the Orphan Nuclear Receptor NR4A2 Predicts Poor Survival in Nasopharyngeal Carcinoma

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantlyassociated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC).Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression wasevaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: Wedid not find a significant association between total NR4A2 expression and clinicopathological variables in 84patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associatedwith tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinicalstage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival ratethan those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysissuggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overallsurvival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potentialunfavorable prognostic factor for patients with NPC.     

Serum Periplakin as a Potential Biomarker for Urothelial Carcinoma of the Urinary Bladder

The objectives of this study were to examine serum periplakin expression in patients with urothelial carcinomaof the urinary bladder and in normal controls, and to examine relationships with clinicopathological findings.Detection of serum periplakin was performed in 50 patients and 30 normal controls with anti-periplakinantibodies using the automatic dot blot system, and a micro-dot blot array with a 256 solid-pin system. Levelsin patients with urothelial carcinoma of the urinary bladder were significantly lower than those in normalcontrols (0.31 and 5.68, respectively; p<0.0001). The area under the receiver-operator curve level for urothelialcarcinoma of the urinary bladder was 0.845. The sensitivity and specificity, using a cut-off point of 4.045, were83.7% and 73.3%, respectively. In addition, serum periplakin levels were significantly higher in patients withmuscle-invasive cancer than in those with nonmuscle-invasive cancer (P = 0.03). In multivariate Cox proportionalhazards regression analysis, none of the clinicopathological factors was associated with an increased risk forprogression and cancer-specific survival. Examination of the serum periplakin level may play a role as a noninvasivediagnostic modality to aid urine cytology and cystoscopy.     

Prognostic Impact of APOBEC3B Expression in Metastatic Urothelial Carcinoma and Its Association with Tumor-Infiltrating Cytotoxic T Cells

APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Here, we evaluated patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy. We performed a retrospective study on 94 patients with urothelial carcinoma who were treated with first line palliative chemotherapy. APOBEC3B expression and CD8+/CD3+ ratio of tumor-infiltrating lymphocytes were evaluated using immunohistochemistry. Kaplan–Meier survival curves were generated and the log-rank test was employed. The association between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. High APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival was longer in patients with high APOBEC3B expression (15 months) than in those with low expression (p = 0.045). The hazard ratio obtained based on the Cox regression analysis was 0.292 (95% confidence interval 0.118–0.723, p = 0.008). APOBEC3B expression was associated with the CD8+/CD3+ ratio (2.914, 95% confidence interval 1.030–8.249, p = 0.039). Collectively, APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells were associated with APOBEC3B expression.     

基于列线图探索脑内皮黏附分子表达水平在结肠癌预后预测中的作用

目的：探索脑内皮细胞黏附分子（CERCAM）与结肠癌患者预后的关系，利用Cox模型建立具有良好预后判断价值的列线图并予以验证。方法：下载TCGA及GTEx数据库中结肠癌及正常组织中CERCAM表达及患者临床特征数据，收集2013年2月至2019年6月南京市第一医院收治的4例结肠癌患者的癌及癌旁组织样本进行验证，通过差异分析、通路富集分析以及生存分析等方法探索CERCAM的组织定位、功能及预后价值。通过Cox回归筛选出结肠癌的预后危险因素，基于CERCAM及各危险因素构建列线图，分别使用一致性指数、校准曲线、时间依赖性受试者工作特征（ROC）曲线进行验证与评价，根据危险分层绘制生存曲线。结果：结肠肿瘤组织中CERCAM基因的表达水平显著低于正常组织（P<0.001），在结肠癌患者中，CERCAM高表达人群OS（P=0.034）及存活状态（P=0.002）显著劣于低表达组，且CERCAM与癌症信号通路以及PI3K-Akt信号通路的活化有关联。Cox分析显示，CERCAM表达水平（HR=2.23，P=0.015）、T分期（HR=5.64，P=0.015）、M分期（HR=2.62，P=0.022）是结肠癌预后的独立危险因素，血管浸润（HR=2.30，P=0.089）是危险因素，利用上述因素建立列线图，一致性指数提示其区分度好，且训练集与测试集一致；校准曲线、ROC曲线同样显示该列线图的预测能力较好。通过危险分层绘制生存曲线，结果提示高风险组有更低的生存率（P<0.000 1）。结论：CERCAM高表达与结肠癌患者不良预后密切相关，且可能与癌症中蛋白聚糖及PI3K-Akt信号通路有关联，基于CERCAM建立的列线图优于传统预测模型，对结肠癌患者生存预后的评估具有一定临床价值，这种实用的模型有助于患者风险分层及治疗方案的优化。