Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma.

PURPOSE: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. PATIENTS AND METHODS: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification. CONCLUSION: The prognostic significance of VCP expression level in GC was demonstrated.     

VCP蛋白表达与胃癌预后的相关性研究

目的：探讨VCP蛋白表达与胃癌预后的关系，确立VCP作为判断胃癌预后的独立因子作用。方法：在187倒胃癌组织手术标本中进行VCP的免疫组织化学染色，比较肿瘤细胞和正常血管内皮细胞VCP的表达，并结合肿瘤浸润、转移、预后等临床因素进行分析比较。结果：VCP的表达与胃癌的浸润、淋巴结转移相关，单变量分析中年龄、胃癌的浸润深度、脉管浸润、淋巴结转移及远处转移等因素显示与胃癌的预后相关（P〈0．05），多变量分析显示了VCP表达水平较肿瘤的分化、淋巴结浸润、转移与胃癌预后相关的危险系数高，故VCP的表达更能反映胃癌的预后。结论：VCP的表达是胃癌重要、独立的预后因子。     

Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.

PURPOSE: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci. RESULTS: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively). CONCLUSIONS: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.     

Expression Level of Valosin Containing Protein is Associated with Prognosis of Primary Orbital MALT Lymphoma

Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated withthe prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expressionin 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty usingmonoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statisticalanalysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALTlymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) accordingto the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCPwas significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-yeardisease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001;P=0.032). There was no observed correlation between the expression level of VCP and other clinical features.Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma.     

赖氨酰氧化酶样蛋白2在头颈部鳞状细胞癌中的表达及临床意义

目的:探讨赖氨酰氧化酶样蛋白2（lysyl oxidase-like 2,LOXL2）在头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）中的表达及与肿瘤转移、预后间的关系。方法:免疫组化检测LOXL2在157例HNSCC患者中的蛋白表达情况,并分析其表达与临床病理特征、转移时间（time to metastasis,TTM）及总生存时间（overall survival,OS）的关系。结果:LOXL2阳性表达患者中位TTM为27.3个月,5年OS为26.1%;而LOXL2阴性表达患者中位TTM为38.6个月,5年OS为47.8%。LOXL2的表达增加与HNSCC中淋巴转移呈正相关(P＜0.05)。结论:HNSCC组织中LOXL2高表达患者更容易发生早期转移,预后更差。LOXL2可能成为一种新的判断头颈部鳞状细胞癌恶性程度和预后的分子标志。     

DJ‐1: A novel independent prognostic marker for survival in glottic squamous cell carcinoma

DJ‐1 is frequently overexpressed in a large variety of solid tumors, but the DJ‐1 expression in laryngeal squamous cell cancer and its clinical/prognostic significance is unclear. We aimed to evaluate DJ‐1 protein expression in glottic squamous cell carcinoma (GSCC) and to correlate this with clinicopathological data including patient survival. The expression of DJ‐1 in GSCCs (60) and adjacent normal tissue (44) was assessed by immunohistochemistry and western blot analysis. In addition, the role of DJ‐1 was investigated in tumorigenesis by transfecting DJ1‐specific siRNA into laryngeal squamous cell carcinoma (LSCC) Hep‐2 cells. Our data showed that positive expression of DJ‐1 was found in 85% of GSCCs. In univariate survival analysis of the GSCC cohorts, a highly significant association between DJ‐1 expression with shortened patient overall survival (5‐year survival rate 92.9%vs 66.6%; P = 0.001; log rank test) was demonstrated. In multivariate analyses, DJ‐1, tumor grading, and pT status were significant prognostic parameters for shortened patient overall survival. Furthermore, siRNA targeting DJ‐1 can effectively inhibit DJ‐1 expression, resulting in enhanced apoptosis and less proliferation of Hep‐2 cells. We concluded that DJ‐1 overexpression might be a novel independent molecular marker for poor prognosis (shortened overall survival) of patients with GSCC. (Cancer Sci 2010; 101: 1320–1325)     

肝细胞癌患者外周血中miR-30a、miR-106b的表达及其与预后的关系

目的:探讨肝细胞癌(hepatocellular carcinoma,HCC)患者血清miR-30a、miR-106b的表达及其与 预后的关系。方法:选取2015年6月-2017年2月本院收治的HCC患者80例为研究对象,20例同期健康人群作为对照组。荧光定量PCR检测外周血中miR-30a、miR-106b的表达水平,分析患者血清miR-30a、miR-106b水平与HCC临床病理的关系。分析HCC患者预后的影响因素以及血清miR-30a、miR-106b水平与HCC患者预后的相关性。结果:HCC患者血清miR-30a表达水平（1.03±0.02）低于正常人群（5.15±0.06）（P=0.00）;血清miR-106b表达水平（2.62±0.35）高于正常人群（1.15±0.06）（P=0.00）。miR-30a、miR-106b表达与患者肿瘤直径、组织分化类程度、肝内转移、淋巴结转移、甲胎蛋白（AFP）水平、门静脉癌栓、肿瘤数目及TNM分期有显著相关性(P＜0.05) 。miR-30a低表达组患者3年总生存率（39.8%）低于miR-30a高表达组（64.6%）（P=0.002）;miR-106b低表达组患者3年总生存率（75.8%）高于miR-106b高表达组（51.2%）（P=0.003）。二元Logistic回归分析提示,淋巴结转移、TNM分期、miR-106b及miR-30a水平是患者预后的重要影响因素。结论:miR-30a在HCC患者血清中低表达,miR-106b在HCC患者血清中高表达,与肿瘤的进展、预后不良有关。     

406例鼻咽癌患者颈部及Ⅴ区后缘间隙淋巴结转移的预后分析

  目的  回顾性分析鼻咽癌患者伴有颈部及Ⅴ区后缘间隙淋巴结转移的预后情况,为颈部淋巴结分区及鼻咽癌N分期的进一步修订提供参考。  方法  选取2011年12月至2016年6月成都军区总医院经病理确诊为鼻咽癌的患者406例,分析伴有颈部及Ⅴ区后缘间隙淋巴结转移患者的预后情况。  结果  406例患者的5年总生存率（overall survival,OS）、无进展生存率（progressionfree survival,PFS）、无局部复发生存率（local relapse-free survival,LRFS）、无远处转移生存率（distant metastasis-free survival,DMFS）分别是75.0%、63.4%、87.2%和81.8%。伴有Ⅴ区后缘间隙淋巴结转移患者的3年OS、PFS、LRFS、DMFS分别是51.5%、22.7%、90.0%和41.3%。N3期患者伴或不伴有Ⅴ区后缘间隙淋巴结转移的3年OS、PFS、LRFS、DMFS分别是43.9%和84.7%（P=0.002）、12.9%和55.4%（P=0.006）、88.9%和80.3%（P=0.649）、33.0%和85.9%（P＜0.001）。单因素分析显示N分期是影响OS、PFS、DMFS的预后因素（P＜0.05）,多因素分析显示Ⅴ区后缘间隙淋巴结转移是影响DMFS的独立预后因素（P＜0.05）。  结论  鼻咽癌患者伴有Ⅴ区后缘间隙淋巴结转移预后差,且该区淋巴结转移预示患者远处转移的风险增加。建议将Ⅴ区后缘间隙作为头颈部肿瘤一个新的颈部分区。      

胰腺癌术后生存率的影响因素

目的:探讨影响胰腺癌术后生存率的影响因素.方法:回顾性分析2010年1月至2012年12月本院178例行胰十二指肠切除术治疗的胰腺癌患者(研究组)以及81例同期健康体检者(对照组)的临床资料,分析术后生存率的影响因素.单因素分析采用Logistic二元回归模型,筛选有统计学意义的指标纳入COX风险回归模型进行多因素分析.结果:Kaplan-Meier结果显示,178例患者术后1年、2年、3年总体生存率分别为56.2%、18.0%、1.7%.单因素分析结果表明,性别、年龄、肿瘤位置与术后生存率无相关性(P>0.05);而肿瘤大小、肿瘤分化程度、临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平与术后生存率有相关性(P<0.05).COX多因素回归分析显示,临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平对患者术后生存率的影响差异有统计学意义(P<0.05),是影响术后生存率的独立危险因素.患者术前、术后1周血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9表达水平显著高于对照组(P<0.05),而术后1个月的表达水平与对照组差异均无统计学意义(P>0.05).患者术后血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9表达水平均逐渐下降,术后1个月的表达水平均显著低于术前(P<0.05).患者术后1个月 sPLA2-ⅡA、CD44v6、CA19-9表达水平显著低于术后1周(P<0.05),整合素β1表达水平和术后1周差异无统计学意义(P>0.05).sPLA2-ⅡA、CD44v6、整合素β1和CA19-9低表达患者的术后生存率均显著高于高表达的患者(P<0.05).结论:在进行胰腺癌治疗时应特别注意临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平等影响预后的独立危险因素,以提高生存率.     

鼻咽癌放化疗后骨转移的治疗及预后分析

目的：分析鼻咽癌放化疗后骨转移的治疗疗效及预后因素。方法：回顾性分析2003年－2011年在钦州市第一人民医院接受鼻咽癌放化疗后5年内发生骨转移的126例患者的治疗及预后。Kaplan －Meier 法计算生存率,Log －rank 法行单因素预后分析,Cox 回归模型行多因素预后分析。结果：5年随访率为98．4％。全部患者1、2、3、5年生存率分别为69．8％、50．0％、34．9％、15．9％。年龄、性别、治疗前 T 分期、治疗前 N 分期、治疗前2D －CRT 或 IMRT 放疗模式,对患者骨转移后1、2、3、5年生存率无影响（P ＞0．05）。骨转移数目≤3个与骨转移＞3个,1、2、3、5年生存率比较,差异有统计学意义（P ＜0．05）;单纯骨转移与骨转移合并其他脏器转移,1、2、3、5年生存率比较,差异有统计学意义（P ＜0．05）;放化疗为主的治疗与化疗为主的治疗比较,1、2、3、5年生存率比较,差异有统计学意义（P ＜0．05）。多因素分析显示骨转移数目＞3个、骨转移合并其他脏器转移、化疗为主的综合治疗模式是影响预后的因素（P ＝0．000）。结论：鼻咽癌治疗后骨转移灶数目≤3个、无其他脏器转移、放化疗为主的综合治疗模式是疗效显著的因素。     

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。     

结直肠癌组织中ARID1A基因突变和MSH2蛋白表达与临床病理特征及预后的相关性

目的:检测结直肠癌（CRC）组织中富含AT结合域1A（ARID1A）基因突变和 mutS同种组织蛋白2(MSH2)蛋白表达,分析两者的临床意义。方法:选取自2017年1月至2018年1月期间我院诊治的142例CRC患者作为研究对象。采用直接测序法检测CRC癌组织中ARID1A基因突变。免疫组化检测癌及癌旁组织MSH2蛋白表达。Spearman秩相关分析ARID1A基因突变和MSH2蛋白表达的相关性。统计学分析ARID1A基因突变、MSH2蛋白表达与CRC临床病理特征的关系。Kaplan-Meier生存分析ARID1A基因突变和MSH2蛋白表达对患者生存预后的影响。单因素及多因素Cox回归分析影响CRC患者生存预后的因素。结果:142例CRC癌组织中,27例发生ARID1A基因突变,ARID1A基因突变率为19.01%（27/142）。MSH2棕黄色阳性表达主要位于细胞核。CRC癌组织中MSH2阳性率为51.41%（73/142）,明显低于癌旁组织91.55%（130/142）（χ2=56.116,P=0.000）。不同肿瘤TNM分期、淋巴结转移CRC癌组织中ARID1A基因突变、MSH2阳性率差异具有统计学意义（P＜0.05）。CRC癌组织中ARID1A基因突变和MSH2表达呈显著负相关性(r=-0.575,P=0.000)。ARID1A基因突变组患者3年总体生存率为37.04%（10/27）,明显低于野生型组患者67.27%（74/110）（P=0.000）;MSH2阳性表达组患者3年总体生存率为81.43%（57/70）,明显高于阴性表达组患者42.30%（27/67）（P=0.000）。ARID1A基因突变型、MSH2阴性表达、肿瘤TNM分期Ⅲ期及伴淋巴结转移是影响CRC患者预后的独立危险因素（P＜0.05）。结论:ARID1A基因、MSH2表达与CRC患者肿瘤分期及淋巴结转移有关,是CRC患者预后预测的独立因素。     

TS和MMR联合检测在结直肠癌预后判断中的作用

目的:对133例结直肠癌患者临床病例资料进行回顾性分析,分析胸苷酸合成酶(thymidylate synthase,TS)蛋白与错配修复(mismatch repair,MMR)状态联合检测与结直肠癌患者临床病理特征及预后之间的关系.方法:免疫组化测定TS和MMR(MLH-1/MSH-2)蛋白表达.根据TS蛋白和MMR状态差异进行相应的配对组合,将纳入患者分为四组:TS蛋白高表达/MMR蛋白高表达(HtHm)组、TS蛋白低表达/MMR蛋白高表达(LtHm)组、TS蛋白低表达/MMR蛋白低表达(LtLm)组、TS蛋白高表达/MMR蛋白低表达(HtLm)组.分析TS和MMR联合检测与患者临床病理因素及预后的关系.结果:TS和MMR联合检测生存分析显示,LtHm组患者(39例)的3年生存率为69.2%,HtLm(20例)组患者的3年生存率为40.0%,两组总体生存率具有统计学差异(P=0.012),该差异在术后辅助化疗患者中仍存在(P=0.011).结论:辅助化疗组患者中LtHm组总体生存率显著高于HtLm组,LtLm组患者较HtHm组患者更易从氟尿嘧啶类药物辅助化疗中获益.     

Prognostic Value of Histopathological Therapeutic Effects and Mitotic Index in Locally Advanced Breast Cancers after Neoadjuvant Chemotherapy

A study was conducted to examine whether or not the histopathologicaltherapeutic effects of preoperative chemotherapy could be usefulfor determining prognosis in women with locally advanced breastcancer. The patients were 37 women with locally advanced breastcancer who received preoperative chemotherapy between 1977 and1987. The histological grade of malignancy (HGM) and histopathologicaltherapeutic effects of chemotherapy (TEf) were examined in resectedspecimens. Patients with HGM 3 showed a poorer 10-year overallsurvival (38%) than those with HGM 1 or 2 (62%). Patients showinga better histopathological response (TEf 1b plus 2) had a poorer10-year overall survival (20%) than those with a poorer response(TEf 0 plus 1a) (60%). Therapeutic effects were significantlyrelated to histological grade, nuclear atypia and mitotic index(P=0.03, 0.005 and 0.002, respectively). Histopathological therapeuticeffects were not directly correlated with patient prognosis.Cox proportional hazard regression analysis revealed that mitoticindex was the most significant prognostic factor related to10-year overall survival.     

首诊Ⅳ期乳腺癌骨转移患者的临床病理特征及预后分析

  目的  探讨首诊Ⅳ期乳腺癌骨转移（initially diagnosed stage Ⅳ breast cancer bone metastasis,IDBCBM）患者的临床病理特征、治疗和预后的关系。  方法  回顾性分析2007年3月至2016年11月天津医科大学肿瘤医院收治的74例IDBCBM患者的临床资料,并行单因素分析和采用Cox回归模型进行多因素分析。  结果  患者的中位年龄为53.3岁。中位总生存时间（overall survival,OS）为34.3个月,3年和5年的生存率分别为37.8%和12.2%。首发转移模式仅为骨转移的患者预后较好,中位生存时间为41.7个月,3年和5年的总生存率分别为54.5%和20.4%。在单因素分析中,分子亚型、激素受体状态、HER-2表达情况、淋巴结状态、Ki-67指数、骨转移数目（number of bone metastasis,NBM）、初始转移模式、药物治疗模式及局部治疗与预后相关;74例IDBCBM患者的Cox回归模型多因素分析显示首发骨转移模式,NBM,药物治疗模式,Ki-67均是影响患者OS的独立预后因素（均P < 0.05）。  结论  Ki-67的高表达、单一的药物治疗模式、NBM较多、骨合并内脏转移均与患者预后较差相关,但局部的手术和放疗是否获益尚无定论。