Predictive and Prognostic Roles of Ribonucleotide Reductase M1 in Patients with Pancreatic Cancer Treated with Gemcitabine: A Meta-analysis

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictorof survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy afteroperative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimedto assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated withgemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web ofScience, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysiswas performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals(CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreaticcancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that highRRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56,95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) thanlow RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests thathigh RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated withadjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker forgemcitabine response and prognosis in pancreatic cancer patients.     

RRM1 mRNA 表达水平与晚期 NSCLC 吉西他滨维持治疗疗效的相关性分析

目的：探讨晚期NSCLC组织中RRM1 mRNA表达水平及其与吉西他滨维持治疗疗效的相关性。方法通过液相芯片法检测40例晚期NSCLC患者肿瘤组织中RRM1 mRNA表达水平，分析RRM1 mRNA表达水平与患者临床特征、吉西他滨维持治疗有效率、无进展生存及总生存时间的相关性。结果 RRM1 mRNA低表达与高表达患者在各临床特征方面无显著差别，两组总生存时间比较无统计学差异（15．6个月 vs 12．1个月，P＝0．582），但RRM1 mRNA低表达患者具有更高的疾病控制率（85．7％ vs 52．6％，P＝0．023）和更长的无进展生存时间（7．0个月 vs 4．5个月，P＝0．025）。结论晚期NSCLC 肿瘤组织中RRM1 mRNA低表达患者吉西他滨维持治疗疾病控制率更高；无进展生存时间更长，RRM1 mRNA是独立的预后因素，适合作为筛选吉西他滨维持治疗获益人群的指标。     

Efficacy of gemcitabine in patients with non-small cell lung cancer according to promoter polymorphisms of the ribonucleotide reductase M1 gene.

PURPOSE: High ribonucleotide reductase M1 (RRM1) expression in resected lung cancers has been associated with better clinical outcomes. However, gemcitabine-treated patients with high tumoral RRM1 expression generally evidence poor prognoses due to the decreased efficacy of gemcitabine therapy. This study was designed in accordance with the hypothesis that polymorphisms (-37 and -524) of the RRM1 promoter gene sequence, which regulate RRM1 expression, could influence the efficacy and prognosis of lung cancer patients treated with gemcitabine-based chemotherapy. EXPERIMENTAL DESIGN: A retrospective dataset of 97 patients with advanced non-small cell lung cancer treated with gemcitabine regimens as a first-line treatment was studied in this work. The allelotyping of RRM1 promoter polymorphisms was conducted via real-time PCR using genomic DNA obtained from peripheral WBC. RESULTS: The RRM1 promoter allelotype was RR37CC-R524TT in 58 patients, RR37AC-RR524CT in 29 patients, and other allelotypes in 10 patients. The response rate for gemcitabine-containing chemotherapy was 49.5%. The response rate was significantly higher in the RR37AC-RR524CT group (65.5%) compared with the group containing other allelotypes (42.6%; P = 0.039). Overall survival and progression-free survival did not differ significantly by allelotype. CONCLUSIONS: We detected significant differences in response rates to gemcitabine-based chemotherapy according to the allelotypes of the RRM1 promoter sequence, which could be determined using the germline DNA. Further functional and clinical studies will be required before this can be used as a predictive marker.     

Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy

The aim of the present study was to evaluate the correlation between excision repair cross-complementation group 1 (ERCC1) protein with the clinical outcome of nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based induction chemotherapy. One hundred one Stage III-IVB nonkeratinizing NPC patients who were treated with cisplatin (DDP)+fluorouracil (5-Fu) induction chemotherapy were recruited. Pre-treatment tumor biopsy specimens were analyzed for ERCC1 by immunohistochemistry. The relationship of ERCC1 expression and chemotherapy response and survival of these NPC patients was analyzed. The objective response to induction chemotherapy of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 88.2% vs. 72% (P=0.041). The 5-year distant failure-free survival (D-FFS) of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 73.5% vs. 51.3% (P=0.037). ERCC1 expression was a significant prognostic factor for overall survival and D-FFS using Cox regression analysis. High tumor ERCC1 expression predicts low chemotherapy response and poor survival mainly caused by more metastasis in locoregionally advanced NPC treated with cisplatin-based induction chemotherapy.     

Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC. PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P =.001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1-positive (n = 88) and those who were EBNA-1-negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1-positive patients and only one of 36 EBNA-1-negative patients developed distant metastases (P =.00015). Kaplan-Meier estimates of overall survival (P =.0010), metastasis-free survival (P =.0004), and progression-free survival (P =.0004) were significantly lower for the patients in the EBNA-1-positive group than for those in the EBNA-1-negative group. Multivariate Cox analysis confirmed the same results. CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.     

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer

Aim： This study explored the correlation between the expression of excision repair cross-complementation group 1 （ERCC1） and the prognosis of gastric cancer patients. Methods： From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry （IHC） was used to assess the expression of ERCCI in resected samples. The relationship between ERCCI expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time （MST） and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. Results： ERCC1 expression was positive in 412 patients （68.1%）. There is no significant difference between ERCCl-positive group and ERCCl-negative group in terms of the MST and 5-year survival rate （P=0.455）. The MST and 5-year survival rate have no significant difference （P=0.162） between group with chemotherapy and group with no chemotherapy in patients with ERCCl-positive expression. However, the MST and 5-year survival rate in patients with ERCCl-negative expression benefited more from with chemotherapy （P=0.019）. The ERCCl-positive patients survived longer than those ERCCl-negative patients （P=0.183） in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC 1 expression had no significant relationship with overall survival in patients with stage II or llI gastric cancer （P〉0.05）. Conclusions： ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCC     

ERCC1 expression as a prognostic marker in N2(+) nonsmall-cell lung cancer patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy

BACKGROUND.: Excision repair cross-complementation Group 1 (ERCC1) overexpression is associated with resistance to cisplatin-based chemotherapy in patients with nonsmall-cell lung cancer (NSCLC). A preliminary study also suggested that ERCC1 expression is associated with radioresistance in lung cancer cells. The aim of this study was to evaluate the clinical implications of ERCC1 expression in stage IIIA N2-positive NSCLC patients treated with platinum-based neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. METHODS.: Sixty-eight patients with mediastinoscopy-proven N2-positive NSCLC were enrolled between August 1997 and September 2003. ERCC1 expression was assessed by immunohistochemistry from pretreatment mediastinoscopic biopsy specimens. RESULTS.: ERCC1 expression was positive in 31 of 68 specimens (46%). Among 14 patients who obtained pathologic complete response, 6 were positive for ERCC1 expression and 8 were negative (P = .818). On univariate analysis, with median follow-up of 61.8 months (range, 34.3-108.8 months), progression-free survival was 15.9 months for ERCC1-positive and 29.5 months for ERCC1-negative patients (P = .062), and there was a statistically significant difference in overall survival between ERCC1-negative tumors and ERCC1-positive tumors (89.2 vs 26.0 months, P = .014). On multivariate analysis, ERCC1 negativity (P = .041) and achieving mediastinal nodal clearance (downstage to pathological N0 or N1) after neoadjuvant CCRT followed by surgery (P = .005) were significant independent prognostic factors for the prolongation of survival. CONCLUSIONS.: These results suggest that N2-positive NSCLC patients with ERCC1 negative tumors show a survival benefit from neoadjuvant CCRT with a platinum-containing regimen. Cancer 2008. (c) 2008 American Cancer Society.     

肺癌组织中RRM1表达对预测GP化疗方案疗效的作用

目的 探索核糖核苷还原酶亚单位RRM1在晚期非小细胞肺癌中的表达及其与吉西他滨化疗敏感性及效果的关系.方法 采用免疫组化S-P法检测30例Ⅲb、Ⅳ期给予GP方案化疗(吉西他滨+顺铂)的非小细胞肺癌患者RRM1的表达情况,并分析其与化疗效果的关系.结果 RRM1表达与性别、年龄、病理类型以及TNM分期差异均无统计学意义(P＞ 0.05).RRM1阳性表达组化疗有效率为12.5%,1年生存率为6.3%;RRM1阴性组化疗有效率为78.5%,1年生存率为64.3%,经统计学分析两组差异有统计学意义(P＜0.05).结论 RRM1对GP方案化疗疗效及生存的预测呈负相关关系,可以作为预测晚期非小细胞肺癌GP方案化疗敏感性及生存预测的参考指标.     

外周Ｔ细胞淋巴瘤ＭＵＭ１／ＩＲＦ４蛋白的表达及其临床意义

目的　研究ＭＵＭ１／ＩＲＦ４蛋白在外周Ｔ细胞淋巴瘤（ＰＴＣＬ）中的表达及临床意义。方法　应用免疫组织化学ＳＰ法检测４６例初治、诊断及分型明确的ＰＴＣＬ患者组织标本中ＭＵＭ１／ＩＲＦ４的表达,分析其表达与患者的临床病理特征、近期疗效及生存的关系。结果　４６例ＰＴＣＬ患者的ＭＵＭ１／ＩＲＦ４阳性表达率为７８.２％。ＭＵＭ１／ＩＲＦ４阴性表达者的有效率为８０.０％,高于阳性者的４６.７％（Ｐ＜０.０５）。全组患者的中位生存期为３１.９个月（９５％ＣＩ：２６～３４个月）,ＭＵＭ１／ＩＲＦ４阴性表达者为２８.０个月,阳性表达者为１５.０个月,差异有统计学意义（Ｐ＝０.０２６）。ＭＵＭ１／ＩＲＦ４阴性表达者的中位无进展生存期为１９.０个月,阳性表达者为１１.７个月,差异有统计学意义（Ｐ＝０.０４１）。结论　ＭＵＭ１／ＩＲＦ４蛋白在ＰＴＣＬ中过表达提示预后不良,可作为判断ＰＴＣＬ预后的指标之一。     

诱导化疗联合同期放化疗对局部晚期鼻咽癌的远期疗效

背景与目的:诱导加同期放化疗有提高鼻咽癌患者无瘤生存率和总生存率的趋势,本研究对比鼻咽癌接受单纯放疗或诱导加同期放化疗的生存率差异,探讨增加诱导及同期化疗对鼻咽癌生存率的影响.方法:将1997年1月至1998年12月在中山大学肿瘤防治中心接受诱导加同期顺铂联合氟尿嘧啶方案化疗3～5疗程联合放疗75例鼻咽癌与同时期接受单纯根治性放疗的局部晚期住院患者460例的生存期进行比较.生存相关分析用Cox回归分析,组间生存率比较采用Kaplan-Meier法.结果:两组间生存率和无瘤生存率差异有统计学意义,放疗加化疗组优于单纯放疗组(P＜0.05).Ⅲ期患者组单纯放射治疗者中位生存期和中位无瘤生存期分别为85.1个月和82.9个月,而化疗加放疗组为94.5个月和89.5个月,两组差异有统计学意义(P＜0.05).Ⅳa期患者组单纯放射治疗者中位生存期和中位无瘤生存期分别为44.4个月和40.3个月,化疗加放疗组为82.4个月和69.6个月,两组差异同样有统计学意义(P＜0.05).Cox回归分析显示,临床分期和化疗与否是独立预后因素.结论:诱导化疗加同期放化疗治疗鼻咽癌可提高Ⅲ、Ⅳa期患者的生存率.     

Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy

Caveolin-1 was up-regulated in different drug-resistant cancer cell lines and was suggested to confer drug resistance by different mechanisms. However, the relation of caveolin-1 expression and the clinical response to chemotherapy and prognosis in non-small cell lung cancer (NSCLC) remains unknown. Total 73 NSCLC (stages IIIB and IV) patients who received gemcitabine-based chemotherapy and also had tumour specimens available before treatment were assessed for caveolin-1 expression using immunohistochemistry. Immunoreactivity of caveolin-1 was correlated with the response to chemotherapy, the clinicopathologic features, and the progression-free survival (PFS) and overall survival (OS) of all patients. Positive caveolin-1 immunostaining was found in 12 (16.4%) of the 73 patients. Eight of the twelve had disease progression and the other four patients remained stable after chemotherapy. Patients with caveolin-1 expression had a significantly lower response rate (complete or partial response, 0% versus 37.7%; P=0.01) and a poor PFS and OS (median survival time: PFS, 4.6 months versus 6.1 months, P=0.005; OS, 7.0 months versus 14 months, P<0.001) than those without caveolin-1 expression. Moreover, multivariate analyses indicated that caveolin-1 positivity was an independent prognostic factor for disease-free survival (DFS) (P=0.003) and OS (P=0.008), respectively. Caveolin-1 expression significantly correlated with drug resistance and a poor prognosis in advanced NSCLC patients treated with gemcitabine-based chemotherapy.     

Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy

PURPOSE: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. EXPERIMENTAL DESIGN: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. RESULTS: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score 相似文献   

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2',2'-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy.     

鼻咽癌HSP70表达与血清EB病毒IgA/VCA的关系及其临床意义

背景与目的:热休克蛋白(HSP)70在许多恶性肿瘤中均有表达,但在鼻咽癌组织中的表达与血清IgA/VCA滴度及预后的关系尚不清楚。本研究旨在检测鼻咽癌组织中HSP70的表达和含量水平,探讨HSP70表达与鼻咽癌患者血清EB病毒IgA/VCA滴度及预后的关系。方法:采用SP免疫组化法检测38例鼻咽癌组织中HSP70表达,ELISA法检测38例鼻咽癌组织中HSP70含量,免疫酶标法检测38例鼻咽癌患者血清IgA/VCA滴度。结果:HSP70在38例鼻咽癌组织中表达率为60.5%。在不同性别、年龄、T分期、N分期和临床分期鼻咽癌组织中HSP70表达率均无显著性差异(P>0.05)。HSP70表达和含量与血清EB病毒抗体IgA/VCA滴度呈正相关(P=0.001)。HSP70阳性组和阴性组患者的5年生存率分别为65.2%和80.0%,5年无瘤生存率分别为40.0%和78.6%(P=0.04)。结论:HSP70在临床Ⅱ、Ⅲ期鼻咽癌患者癌组织中的表达与患者的IgA/VCA滴度正相关,HSP70阳性患者常规治疗后预后较差。     

P53表达对晚期上皮性卵巢癌一线化疗方案选择的意义

背景与目的:目前,上皮性卵巢癌的术后一线化疗方案主要包括铂类联合紫杉醇(TC)和铂类联合环磷酰胺(PC)。本研究拟观察分子标记物P53表达与上述两种化疗方案疗效的关系,分析P53表达在化疗疗效预测上的价值,探讨检测P53表达在选择化疗方案上的意义。方法:回顾性分析53例以TC或PC作为术后一线化疗方案的Ⅲc期上皮性卵巢癌,用免疫组化方法检测标本的P53表达,比较P53阳性组和P53阴性组中各化疗方案的完全缓解(completeresponse,CR)率和无进展生存时间(progression-freesurvival,PFS),并行多因素分析影响PFS的预后因素。结果:53例患者中22例P53阳性,其中13例采用TC方案,CR10例(76.9%),中位PFS102周;9例采用PC方案,CR3例(33.3%),中位PFS43周。TC组CR率稍高于PC组(P=0.05),TC组患者PFS长于PC组(P=0.04)。对31例P53阴性患者采用不同化疗方案治疗的CR率和PFS无显著性差异(P>0.05)。多因素分析提示残留病灶大小是独立预后因素。结论:检测P53表达在选择化疗方案上可能有意义。对于P53阳性患者首选TC方案,对于P53阴性患者可以选择PC或TC方案。确切结论尚需进一步在大样本前瞻性研究中验证。     

Clinical significance of cyclooxygenase-2 expression in extranodal natural killer (NK)/T-cell lymphoma, nasal type

PURPOSE: To determine whether there are any differences in therapeutic response, patterns of systemic recurrence, and prognosis of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, by the cyclooxygenase-2 (COX-2) expression. PATIENTS AND METHODS: Thirty-four patients with Ann Arbor Stage I and II extranodal NK/T-cell lymphoma who underwent chemotherapy or radiotherapy, or both, were retrospectively reviewed. These patients were divided into two groups according to their immunohistochemical staining for COX-2 expressions: a COX-2-negative group (n = 10 patients) and a COX-2-positive group (n = 24 patients). The treatment response, patterns of treatment failure, and survival data for the patients were compared between the COX-2-positive and negative groups. RESULTS: There was no significant difference in the clinical profiles between the COX-2-negative and COX-2-positive groups. All patients (100%) in the COX-2-negative group achieved complete response after initial treatment, whereas only 14 patients (58%) in the COX-2-positive group achieved complete response (p = 0.03). Compared with the patients in the COX-2-negative group, those in the COX-2-positive group had a significantly lower 2-year systemic recurrence-free survival rate (100% for the COX-2-negative group vs. 54% for the COX-2-positive group) (p = 0.02) and a decreased 5-year overall survival rate (70% for the COX-2-negative group vs. 32% for the COX-2-positive group) (p = 0.06). CONCLUSION: Cyclooxygenase-2 expression can serve as a predictive factor for poor treatment response, higher systemic recurrence, and unfavorable prognosis in patients with extranodal NK/T-cell lymphoma, nasal type.     

nm23-H1和MUC-1在外周T细胞淋巴瘤中的表达及其临床意义

背景与目的:外周T细胞淋巴瘤(peripheralT-celllymphoma,PTCL)是一类异质性疾病,临床侵袭性较强,常规治疗效果欠佳。国际预后指数(internationalprognosticindex,IPI)在PTCL中的价值尚未确定,有必要寻找一些分子指标来协助预测PTCL的预后。本研究旨在探讨nm23-H1和MUC-1对PTCL预后判断的价值。方法:免疫组化SP法检测中山大学肿瘤防治中心1997年1月至2004年12月间收治的96例初治PTCL患者组织中nm23-H1和MUC-1的表达情况,分析其表达与患者临床特征、近期疗效及远期生存率的关系。结果:96例患者nm23-H1和MUC-1的阳性率分别为81.2%(78/96)和58.3%(56/96);两者表达强度均与病理亚型无明显相关(P>0.05)。nm23-H1高表达与Ⅲ/Ⅳ期、PS状态≥2分、结外侵犯和结外病变数≥2等有关(P﹤0.05);而MUC-1高表达仅与分期Ⅲ/Ⅳ期、结外病变数≥2有关(P<0.05)。89例患者可评价化疗的客观疗效,全组有效率87.8%,完全缓解(CR)率56.7%。nm23-H1阴性者CR率高于阳性者(66.7%vs.55.4%,P<0.05),低表达组CR率高于高表达组(79.9%vs.44.0%,P<0.05);MUC-1阴性和低表达组的CR率分别高于阳性和高表达组,但均无显著性差异(P>0.05)。全组中位随访时间30个月(2～98个月),中位生存期32个月(95%CI26～34个月);nm23-H1阴性组5年生存率(overallsurvival,OS)明显高于阳性组(86.7%vs.24.9%,P=0.001),低表达组5年OS明显高于高表达组(52.3%vs.21.7%,P=0.000);MUC-1阴性组5年OS稍高于阳性组(47.9%vs.28.5%,P=0.260),低表达组5年OS稍高于高表达组(46.2%vs.22.2%,P=0.337)。多因素分析结果显示,IPI评分和nm23-H1表达水平是PTCL独立的预后指标。结论:nm23-H1在PTCL中过度表达提示预后不良,可作为判断PTCL预后的独立指标;MUC-1在PTCL中阳性及高表达与预后不良具一定的相关性,但对预后判断的价值尚不能确定。nm23-H1结合IPI评分等临床指标可能有助于更精确判断PTCL的预后。     

Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy

BACKGROUND: Eg5 is a microtubule motor protein that functions in bipolar spindle assembly. We investigated the relationship between Eg5 expression and the response to chemotherapy of patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eg5 expression was investigated immunohistochemically in 122 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. We also investigated cyclin B1 expression, which is involved in the G2/M transition. All patients received antimitotic agents combined with platinum chemotherapy. The response to chemotherapy was compared in relation to Eg5 and cyclin B1 expression and in relation to clinicopathological factors. RESULTS: The response rate to chemotherapy of patients with Eg5-positive tumors was 37%, as opposed to 10% for patients with Eg5-negative tumors, and Eg5 expression was significantly associated with the response to chemotherapy (P=0.002). The response rate of patients with cyclin B1-positive tumors (53%) was higher than that of patients with cyclin B1-negative tumors (23%) (P=0.009), and Eg5 expression was significantly correlated with cyclin B1 expression (P=0.005). A multivariate analysis confirmed Eg5 status to be an independent variable related to response to chemotherapy (P=0.008). CONCLUSIONS: Eg5 expression can predict a response to antimitotic agents combined with platinum chemotherapy among patients with advanced NSCLC.     

鼻咽癌新鲜肿瘤组织DNA倍体性与预后的关系

背景与目的:因肿瘤有生物学异质性,部分肿瘤的预后和TNM分期并不符合;寻找有效的生物学预后指标作为临床分期的补充,可为今后鼻咽癌的个体化治疗提供一个新的依据.本研究探讨初治鼻咽癌患者新鲜肿瘤组织细胞的DNA倍体性与疗效、预后的关系.方法:1999年1月至2000年2月,53例初治鼻咽癌患者进入本研究,其中单纯放疗32例,另21例患者于放疗第4周接受了一个疗程的PF方案化疗.患者治疗前均活检取新鲜肿瘤组织,用流式细胞仪进行DNA倍体检测.结果:53例患者中,二倍体32例(60.4%),异倍体21例(39.6%).不同倍体组患者的年龄、性别、临床分期、N分期、化疗与否的差异无统计学意义(P=0.695、0.657、0.088、0.972和0.335).全组患者中位随访时间73个月(12～84个月).全组5年总生存率65.61%,其中二倍体组为80.92%,异倍体组为42.86%(P=0.002);5年无远处转移生存率二倍体组为84.26%,异倍体组为44.53%(P=0.003);5年无复发生存率二倍体组为92.59%,异倍体组为72.65%(P=0.118).单因素分析结果显示,临床分期是无复发生存率的影响因素,DNA倍体性、临床分期和T分期是总生存率和无远处转移生存率的影响因素.多因素分析结果显示,与总生存率相关的独立预后因素为DNA倍体性(P=0.020)和临床分期(P=0.007),与无转移生存率相关的预后因素亦为DNA倍体性(P=0.017)和临床分期(P=0.011).结论:采用流式细胞术检测新鲜组织细胞的DNA倍体性和临床分期一样可以预测鼻咽癌患者的预后;DNA异倍体患者比二倍体患者更容易出现远处转移而导致治疗失败.