Expression and prognostic relevance of CD44v6 in stage I non-small cell lung carcinoma

Purpose  

Expression of CD44 and its variants has been shown to be relevant to tumor progression in various human malignancies. We evaluated the expression of CD44v6 in the primary lesions of stage I non-small cell lung cancer (NSCLC) and correlated the expression level to its prognosis.     

血清癌胚抗原与非小细胞肺癌关系的研究进展

血清癌胚抗原是最早用于肺癌诊断及预后评估的肿瘤标志物,尤其是在非小细胞肺癌的早期诊断、预后及疗效评估中尤为重要,但由于其敏感性较低,故目前越来越多研究倾向于联合其他肿瘤指标以提高其敏感性.本文结合近期相关文献,就癌胚抗原与非小细胞肺癌的关系作一综述.     

Serum carcinoembryonic antigen level and pleural lavage cytology in woman with non-small cell lung cancer

BACKGROUND: The prognostic impact of serum carcinoembryonic antigen (CEA) levels and pleural lavage cytology (PLC) in female patients with non-small cell lung cancer (NSCLC) were examined. METHODS: A consecutive series of 122 women with NSCLC who underwent surgical resection and PLC were included in the study. RESULTS: The 5-year survival rate of patients with preoperative serum normal and elevated CEA levels was 86.79 % and 58.46 %, respectively ( P = 0.0032). Positive PLC was present in 9/122 (7.38 %) of patients. The 5-year survival rate of patients with positive PLC findings was 33.33 %, which was significantly poor compared with that of patients with negative findings (83.16 %, P = 0.0010). Multivariate analysis indicated that pN status, preoperative serum CEA levels and PLC findings were independent prognostic factors. CONCLUSIONS: Preoperative serum CEA level and PLC findings were independent prognostic factors for female patients with NSCLC.     

METTL14在非小细胞肺癌中的表达以及预后意义

目的探讨METTL14在非小细胞肺癌(NSCLC)组织中的表达以及与预后之间的相关性。方法收集我院2015年1月-2016年7月收治并行手术切除术的64例NSCLC患者癌变组织(研究组)及相应的癌旁正常组织(对照组),采用实时荧光定量(qRT-PCR)检测组织中METTL14 mRNA的表达,westernblot检测METTL14蛋白表达。比较两组间METTL14的表达与临床病理特征之间的关系,绘制Kaplan-Meier生存曲线,采用多因素Cox回归模型分析独立预后因素。结果METTL14 mRNA在研究组与对照组中的相对表达量分别为(3.03±1.02)、(1.01±0.04),METTL14蛋白在研究组与对照组中的相对表达量分别为(0.21±0.05)、(0.13±0.03),METTL14 mRNA与蛋白在NSCLC癌变组织中的表达较癌旁正常组织高(P均<0.05);TNMⅢ+Ⅳ级、合并淋巴转移的NSCLC患者METTL14高表达的比例较高(P均<0.05),METTL14高、低表达与患者的年龄、性别、病理类型以及吸烟史无关(P均>0.05),METTL14高、低表达的NSCLC患者中位生存时间分别为23.5、34.5个月,总生存率分别为15.63%、46.88%,METTL14低表达的NSCLC患者预后优于METTL14高表达患者(P均<0.05)。Cox回归模型分析发现METTL14高表达、TNMⅢ+Ⅳ级是影响NSCLC患者生存的独立预后因素(P均<0.05)。结论METTL14在NSCLC组织中高表达,且与患者TNM分级、淋巴转移相关,可能参与了NSCLC的发生发展,提示NSCLC患者预后不良。     

Tumor volume is a better prognostic factor than greatest tumor diameter in stage Ia non-small cell lung cancer

OBJECTIVE: The objective was to determine whether tumor volume, calculated by multiplying 3-dimensional diameters recorded from surgical specimens, could represent tumor size more precisely than the currently used greatest tumor diameter (T status) as a prognostic factor in early-stage non-small cell lung cancer (NSCLC). METHODS: From 1991 to 2001, a total of 236 stage Ia NSCLC patients underwent curative resection in our institution. Their clinicopathological factors were retrospectively reviewed. The cases were grouped according to stereographic tumor size. Group 1 included tumor volumes less than 0.5236 (1(3) x pi/6) cm3, Group 2 included tumor volumes between 0.5236 - 4.1888 (2(3) x pi/6) cm3, while Group 3 included tumor volumes between 4.188 - 14.1372 (3(3) x pi/6) cm3. Overall survival and disease-free interval analyses were performed with the Kaplan-Meier method and multivariable Cox's proportional hazard model. Tumor volume and other clinico-pathological factors were included for analysis. RESULTS: Median follow-up was 55.5 months. The overall 5- and 10-year survival rates were 78 % and 71 %, and the 5- and 10-year disease-free intervals were 68 % and 64 %, respectively. The overall survival ( P = 0.0075) and disease-free interval ( P = 0.0025) showed significant differences between tumor volume groups. Smoking history, presence of symptoms and the number of resected lymph nodes were also significantly related to overall survival and disease-free interval. CONCLUSION: The products of 3-D diameters (tumor volume) more precisely evaluated tumor size as well as survival of patients with stage Ia NSCLC.     

RRM1和ERCC1在非小细胞肺癌中的表达及意义

目的探讨DNA修复基因家族成员ERCCl、RRM1在非小细胞肺癌(NSCLC)中的表达及意义。方法应用免疫组织化学PV-9000法对30例NSCLC患者肿瘤组织中的ERCC1、RRM1蛋白表达进行检测。用χ2检验、相关分析、Kaplan-Meier生存曲线进行统计分析。结果 NSCLC患者肿瘤组织中,ERCC1和RRM1表达与患者性别、年龄、分期、病理类型、是否吸烟等参数无明显相关;ERCC1和RRM1的表达呈正相关(r=0.439,P=0.027);ERCC1阴性组的总生存期和无疾病进展生存期均明显长于ERCC1阳性组,RRM1阴性组的总生存期和无疾病进展生存期均明显长于RRM1阳性组(P<0.05或<0.01)。结论 ERCC1和RRM1在NSCLC肿瘤组织中的表达具有相关性,ERCC1和RRM1低表达提示NSCLC患者生存期长、生活质量高,RRM1和ERCC1高表达者对吉西他滨+顺铂化疗耐药,可作为判断其预后的指标,指导临床个体化用药。     

VEGF及C-erbB-2蛋白在NSCLC患者肿瘤组织中的表达及意义

目的探讨血管内皮生长因子（VEGF）及表皮生长因子受体-2（C-erbB-2）表达在非小细胞肺癌（NSCLC）发病中的作用及对患者预后的影响。方法采用免疫组织化学法,对病理确诊的86例NSCLC患者肿瘤组织中VEGF及C—erbB-2蛋白表达进行检测,并与癌旁组织及正常组织进行对比;分析两种指标表达水平与肿瘤临床病理特征及患者预后的关系。结果VEGF及C-erbB-2蛋白在癌旁组织及正常组织中均无或低表达,VEGF在NSCLC肿瘤组织中阳性表达率为52．3％、与肿瘤组织学分级有关,C-erbB-2在NSCLC肿瘤组织中阳性表达率为43．0％、与肿瘤组织学类型及组织学分级有关;VEGF表达阳性及C—erbB-2表达阳性者总生存时间均显著低于阴性者,两者均为影响NSCLC患者预后的独立因素。结论VEGF和C—erbB-2表达在NSCLC发生、发展中具有重要作用,为影响预后的独立因素;临床可有针对性地使用靶向治疗药物。     

Molecular prognostic factors in resectable non-small cell lung cancer

Lung cancer retains the leading position in cancer-related deaths in the western countries. Non-small cell lung cancer (NSCLC) comprises more than 80% of lung cancers, and complete surgical resection of primary tumors in early-stage disease is the only potentially curative treatment. One area of intense research on early-stage NSCLC is the identification of molecular markers to complement TNM staging to fully assess the prognosis of patients and to define innovative strategies. Numerous prognostic factors have been identified in patients with early-stage NSCLC that might enable classification of such patients into different subsets corresponding to different risks of recurrence following complete resection. Most of the markers are proteins that can be detected by immunohistochemistry assays based on the antigen-antibody reaction. The present review aims at providing a panorama on classical as well as new prognostic markers. Of special interest are some molecular factors, already or currently tested from a prognostic point of view, that might also become good candidates for predicting treatment efficacy.     

Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer

OBJECTIVE: The purpose of this study was to determine the relationship between tumor size and survival in patients with stage IA non-small cell lung cancer (non-small cell lung cancer; ie, lesions < 3 cm). METHOD: Five hundred ten patients with pathologic stage IA (T1N0M0) non-small cell lung cancer were identified from our tumor registry over an 18-year period (from 1981 to 1999). There were 285 men and 225 women, with a mean age of 63 years (range, 31 to 90 years). The Cox proportional model was used to examine the effect on survival. Tumor size was incorporated into the model as a linear effect and as categorical variables. The Kaplan-Meier product limit estimator was used to graphically display the relationship between the tumor size and survival. RESULTS: The Cox proportional hazards model did not show a statistically significant relationship between tumor size and survival (p = 0.701) as a linear effect. Tumor size was then categorized into quartiles, and again there was no statistically significant difference in survival between groups (p = 0.597). Tumor size was also categorized into deciles, and there was no statistical relationship between tumor size and survival (p = 0.674). CONCLUSIONS: This study confirms stratifying patients with stage IA non-small cell lung cancer in the same TNM classification, given no apparent difference in survival. Unfortunately, these data caution that improved small nodule detection with screening CT may not significantly improve lung cancer mortality. The appropriate prospective randomized trial appears warranted.     

Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

ObjectiveTo investigate the expression of hENTl and ERCC1 genes in tumor tissues non–small cell lung cancer (NSCLC).MethodsFresh non–small lung cancer specimens were transplanted into nude mice. Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in tumor tissue were detected by real–time fluorescent quantitative PCR. The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated 2–3 times per week. Tissue samples were collected from NSCLC mice treated with gemcitabine plus carboplatin.ResultsThe histological examination showed that many tumor cells were well preserved in nude mice. The rate of transplanted tumor cells was 86.7%. The concomitant treatment study showed that the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC obviously influenced the body weight. Compared with NS group, DDP group, GEM group, the survival period and the level of hENTl of DDP+GEM group increased obviously, the level of ERCC1 decreased significantly (P<0.05).ConclusionsThe expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients with NSCLC treated with gemcitabine plus cisplatin.     

Therapy for stage I and stage II non-small cell lung cancer

Despite complete resection of what seems to be all evident tumor, one third to three quarters of patients with stages I and II NSCLC ultimately succumb to this neoplasm. Patients who are cured of an original NSCLC or small cell cancer remain at risk for a new primary lung cancer. Although the importance of lifelong surveillance is clear, the extent and timing of optimal follow-up remain undefined. Although clinicians refer to the development after treatment of clinically discernible sites of tumor as "recurrence," it is probably more accurate to consider these foci as "persistence"--that is, the locoregional site was not sterilized by surgery, and the distant implants were present from the outset but undetected. Although data are sparse, induction and improved adjuvant therapy for early NSCLC may be helpful. Much further experience is needed. Further study and application of biologic indicators in addition to TNM staging likely will help identify patients at high risk for surgical failure who may benefit by combination treatment.     

Therapy for stage IIIB and stage IV non-small cell lung cancer

The treatment options for unresectable stage III NSCLC include definitive RT, chemotherapy, combined chemoradiotherapy, or supportive care. Compared with radiation alone or chemotherapy alone, the combination of chemotherapy and standard RT confers a modest survival benefit at the cost of increased toxicity for patients with an excellent performance status. For metastatic disease, combination chemotherapy--in particular, platinum-based regimens--improves symptom control and survival. Newer chemotherapeutic agents with higher response rates and favorable toxicity profiles are improving outcome even for the elderly and debilitated patients and those refractory to first-line chemotherapy. Evolving understanding of the molecular events in tumorigenesis is uncovering a host of promising targets for mechanism-based therapy. Many of these novel target modulators likely will require combination with conventional chemotherapy for optimal results.     

分化抗原簇63在非小细胞肺癌中的表达及临床意义

目的 检测分化抗原簇63(cluster of differentiation 63,CD63)在非小细胞肺癌(non-small-cell lung cancer,NSCLC)组织中的表达水平与临床特征和生存的相关性.方法 收集2013年6月至2015年1月在安阳市第二人民医院接受手术治疗的NSCLC患者126例,收...     

The prognostic effect of natural killer cell infiltration to tumoral tissues in stage I non-small cell lung cancer

Lung cancer is the most common type of cancer among males and females in developed countries. Currently, the five-year survival rate of lung cancer patients is 14%. Immune system has been considered to play an important role in the development and metastasis of lung cancer. In this study, natural killer (NK) cell infiltration was evaluated in the tumor tissues of 40 patients with stage I non-small cell lung cancer (NSCLC) to evaluate its effect on the prognosis. The evaluation included the tissue samples of 40 patients who underwent resection due to NSCLC between 1994 and 1998 in Ankara University Medical School, Chest Surgery Department. All the patients had stage I squamous cell carcinoma. The patients were followed-up for 4-8 years postoperatively. NK cell counts varied between 1 and 86 (mean: 13.63 +/- 11.86). The patients were divided into two groups according to their cell counts as low (n= 24) and high (n= 16). The mean survival time of the group with low NK cell count was 52 +/- 6 months and the mean five-year survival rate was 51%. The mean survival time of the group with high NK cell count was 58 +/- 4 months and the mean five-year survival rate was 68%. No statistically significant difference was detected between the two groups for five-year survival time (p= 0.15). As a result, in our study we did not find any significant effect of natural killer infiltration on tumoral tissue in prognosis of stage I NSCLC.     

非小细胞肺癌差异基因的筛选及预后分析

目的利用生物信息学方法分析非小细胞肺癌(NSCLC)基因表达谱芯片,筛选差异基因,分析其与预后的关系。方法从GEO数据库下载芯片数据(GSE19804、GSE27262、GSE18842),利用GEO2R软件筛选差异基因,通过基因本体(GO)和京都基因与基因组百科全书(KEGG)进行差异基因的功能及通路富集分析,用STRING数据库构建蛋白-蛋白相互作用网络,Cytoscape筛选出核心基因。Kaplan-Meier plotter数据库进行预后分析,采用实时荧光定量PCR(QPCR)检测目的基因在NSCLC组织中的表达。结果共筛选出401个差异表达基因,GO分析结果表明差异基因主要参与血管生成、细胞粘附、调节细胞增殖等生物学过程。通过Cytoscape软件筛选出29个核心基因。预后分析显示ASPM低表达患者的总生存期较高表达患者明显延长。QPCR显示ASPM在NSCLC组织中高表达,差异有统计学意义。结论ASPM在NSCLC组织中高表达,与患者的预后相关,可能是NSCLC潜在的治疗靶点。     

Prognostic significance of tumor proliferative fraction and DNA content in stage I non-small cell lung cancer.

Analyses of tumor DNA content and proliferative fraction by flow cytometry have been useful as prognostic determinants in a variety of solid tumors. The significance of this analysis in Stage I (T1N0M0 and T2N0M0) non-small cell lung carcinoma (NSCC) is unestablished. We determined DNA content (ploidy) and proliferative fraction (percentage S phase) on 44 surgically resected Stage I NSCC specimens obtained between 1977 and 1982. All cases had a minimum follow-up of 5 yr. Of the 44 cases, 27 were adenocarcinomas, 15 squamous cell carcinomas, and 2 large cell carcinomas. Of these, 32 (73%) had T1N0M0 lesions and 12 (27%) had T2N0M0 lesions. Overall 5-yr survival was 70%. All patients surviving 5 yr were free of detectable tumor. Patients with T1N0M0 lesions had an 81% 5-yr survival, but those with T2N0M0 lesions had a 42% 5-yr survival (p = 0.009). Analysis of tumor DNA content revealed 35 diploid tumors (79%) and 9 aneuploid tumors (21%). The 5-yr survival for diploid tumors was 77% compared with a 44% 5-yr survival in aneuploid lesions (p = 0.048). The median proliferative fraction was 6%. All patients with a percentage S phase less than 6% survived 5 yr, and 41% (9 of 22) of those greater than 6% survived 5 yr (p less than 0.001). When 8% S phase was used as a cutoff, 93% (28 of 30) below the cutoff survived 5 yr but only 21% (3 of 14) above the cutoff survived 5 yr (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)