Prognosis in HIV-infected patients with non-small cell lung cancer

Background:

We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients.

Methods:

Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders.

Results:

Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5–8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17–23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks.

Conclusion:

NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.     

非小细胞肺癌预后影响因素分析

目的:探讨非小细胞肺癌(NSCLC)患者的预后相关因素。方法:对2005年6月-2006年6月我院收治的162例非小细胞肺癌患者的临床、病理资料进行回顾性研究,采用Kaplan-Meier和COX回归方法分析评价各因素对预后的影响。结果:单因素分析表明KPS评分、手术与否、临床分期、治疗状况及治疗前血小板(PLT)、癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)的水平与NSCLC患者的预后有关。多因素分析表明,临床分期、治疗状况、血小板及血清癌胚抗原的水平是独立的预后影响因素。临床分期Ⅳ期、未治疗、PLT>300×109/L、CEA>5.0μg/L时,相对危险度(RR)分别为5.524、16.096、3.563、2.607。结论:治疗前血小板、血清CEA的水平、临床分期及治疗情况是NSCLC患者独立的预后影响因素。     

早期非小细胞肺癌预后相关因素分析

早期非小细胞肺癌患者首选手术治疗后，仍有部分出现了局部复发和／或远处转移。筛选出预后差的患者辅以综合治疗显得尤为重要。本文分析了近年来研究的一些早期非小细胞肺癌的预后因素。     

SPARC expression and prognostic value in non-small cell lung cancer

Secreted protein,acidic and rich in cysteine(SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value.Moreover,because of its strong affinity for albumin,and hence albumin-bound drugs,SPARC has increasingly become a focus for research.In this study,we aimed to determine SPARC expression in patients with non-small cell lung cancer(NSCLC) and investigate the association of SPARC with disease prognosis.Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center,and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression.Our results showed that SPARC expression status did not significantly relate with age,gender,and tumor stage.However,SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma(75% vs.43.5%,P = 0.004).Patients with smoking history had higher SPARC expression than non-smokers(68.2% vs.33.3%,P = 0.002).In both univariate and multivariate analyses,SPARC was a prognostic factor of overall survival(HR = 0.32;95% CI:0.16-0.65) but not disease-free survival.Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC.Most notably,SPARC can be used as a prognostic factor for NSCLC.     

硫氧还蛋白还原酶-2在非小细胞肺癌中的表达及预后

目的:探讨硫氧还蛋白还原酶-2(thioredoxin reductase-2,TrxR2)在非小细胞肺癌(NSCLC)中的表达及对患者预后的影响.方法:免疫组化法检测90例手术后NSCLC癌组织及癌旁正常肺组织中TrxR2的表达,分析TrxR2表达与患者临床病理特征及生存预后的关系.结果:TrxR2在NSCLC组织中的表达高于癌旁正常组织(P＜0.05),TrxR2的表达与患者性别、是否吸烟、肿瘤组织分级、TNM分期无相关性(P＞0.05),而与年龄及淋巴结转移显著相关(P＜0.05).随访90例患者发现TⅨR2高表达组的患者预后更差(P＜0.05).结论:TrxR2在NSCLC中高表达,有望成为NSCLC转移及预后判断的重要指标.     

PTEN蛋白阳性在非小细胞肺癌的临床意义

目的：研究FTEN蛋白阳性对非小细胞肺癌临床意义。方法：应用免疫组化SP法检测10例正常肺组织和56例非细胞肺癌中PFEN基因的表达。结果：非小细胞肺癌中PTEN蛋白阳性率为59％，而正常组织均阳性。PTEN蛋白阳性与肿瘤组织分化程度、临床分期以及有无淋巴结转移相关。PTEN蛋白阴性者预后较差，结论：从蛋白水平揭示PTEN基因与非小细胞肺癌发展有关．PTEN蛋白的检测有望成为判断非小细胞肺癌预后的参考指标之一。     

胰岛素样生长因子结合蛋白3在非小细胞肺癌中的表达研究

目的:检测胰岛素样生长因子结合蛋白3(IGFBP3)在非小细胞肺癌(NSCLC)组织中的表达,探讨其与肺癌临床病理学特征和生存时间的关系。方法:采用免疫组织化学和免疫印迹技术检测IGFBP3在34例肺鳞癌和25例肺腺癌(共21例含癌旁肺组织)及15例良性肺病变组织中的表达。结果:IGFBP3在良性肺组织中表达定位于细胞质;而在肺癌组织中表达定位于细胞质和细胞核(分别称为IGFBP3质表达和核表达),后二者阳性率为44%(26/59)和29%(17/59)。IGFBP3使表达在肺癌和良性肺组织间差异无统计学意义。在伴有局部淋巴结转移肺癌组织中IGFBP3核表达显著低于无淋巴结转移肺癌组织,P=0.0029;在低分化肺癌组织中IGFBP3核表达显著低于中或高分化肺癌,P=0.0292。IGFBP3质表达与胰岛素样生长因子1(IGF1)在肺癌组织中的表达显著相关,P=0.0007。IGFBP3质表达阳性者预后差,而IGFBP3核表达阳性者预后优于阴性表达者。结论:在NSCLC组织中,IGFBP3质表达可能与调节IGF作用有关,而核表达则可能与抑制肿瘤生长有关,IGFBP3质或核表达具有一定的预后意义。     

DEK蛋白在非小细胞肺癌中的表达及临床意义

目的:探讨DEK蛋白在非小细胞肺癌中的表达及意义.方法:免疫组织化学方法检测DEK蛋白在非小细胞肺癌中的表达情况以及和临床病理因素的相关性.结果:DEK蛋白在非小细胞肺癌中阳性率65.9％.DEK高表达与分化程度呈负相关(r=-0.173,P=0.021);与pTNM分期(r=0.160,P=0.033)和淋巴结转移(r =0.195,P=0.009)呈正相关.DEK高表达的NSCLC患者生存时间低于DEK低表达的NSCLC患者(P=0.021).结论:DEK是一种癌蛋白,可作为一种新的肿瘤标记物,深入研究DEK可能会为肺癌恶性生物学行为变化提供干预的靶点.     

Prognostic factors in patients with stage IV non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths among both men and women over the world. In 2002, lung can- cer accounted for more deaths than breast cancer, prostate cancer, and colon cancer combined[1]. Non-small cell lung cancer (NSCLC) represents 75%–85% of all lung cancers. Lung cancer is hard to discovered until it’s at an advanced stage and the outlook for recovery is poor. Approximately two-thirds of NSCLC patients have advanced-stage at di- agnosis. Stage IV NSCLC denotes …     

Ⅳ期非小细胞肺癌预后影响因素分析

Objective: To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P＜0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis.Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis,anatomic typing,KPS,appetite,body weight loss,cycles of chemotherapy.     

非小细胞肺癌根治术后生存分析

目的 肿瘤的局部复发和远处转移是非小细胞肺癌(non-small cell lung cancer,NSCLC)治疗失败和死亡的最主要原因.本研究评价与NSCLC患者复发/转移后生存时间(postrecurrence survival,PRS)和总生存率(overall survival,OS)相关的临床病理因素.方法 回顾性分析2005-01-01-2011-12-31于中日友好医院胸外科行肺叶切除+纵隔淋巴结清除的160例NSCLC患者临床资料及随访资料,病理分期为p I A～ⅢA期且经过随访均发生局部复发或者远处转移,应用SPSS 20.0对资料进行统计分析.应用Kaplan-Meier曲线及Cox回归对根治性切除术后OS和PRS相关风险因素进行分析.结果 160例患者平均年龄62岁,其中鳞癌41例,腺癌101例,其他类型NSCLC 18例(腺鳞癌11例,大细胞癌7例).随访终点43例发生局部复发,93例发生远处转移,24例同时发生局部复发和远处转.入组患者中位生存时间45个月;复发/转移后中位生存时间20个月.单因素分析结果显示,性别、TNM分期和复发/转移与OS有相关性,P＜0.05;年龄、吸烟指数、吸烟史、病理类型、淋巴血管浸润、复发/转移时间≤12个月、复发转移时间≤24个月、术后有无(放)化疗以及复发后有无治疗亦与OS具有相关性,P＜0.01.多因素分析结果显示,年龄(HR=0.23,95％CI:0.14～0.38,P＜0.01)、吸烟指数(HR=11.28,95％CI:2.53～50.26,P＜0.01)、TNM分期(HR=1.50,95％CI:1.08～2.07,P＜0.05)、复发时间≤24个月(HR=0.31,95％CI:0.16～0.60,P＜0.01)、术后有无放化疗(HR=0.82,95％CI:0.68～0.99,P＜0.05)、复发后有无治疗(HR=1.40,95％CI:1.24～1.58,P＜0.01)为影响OS的独立危险因素.单因素分析结果显示,年龄、吸烟指数、病理类型、TNM分期、术后有无(放)化疗和复发后有无治疗与PRS有相关性,P＜0.01;复发/转移亦与PRS有相关性,P＜0.05.多因素分析结果显示,年龄(HR=0.26,95％CI:0.18～0.45,P＜0.01)、吸烟指数(HR=1.73,95％CI:1.12～2.68,P＜0.05)、术后有无(放)化疗(HR=0.77,95％CI:0.66～0.91,P＜0.01)、复发后有无治疗(HR=1.36,95％CI:1.22～1.52,P＜0.01)为影响PRS的独立危险因素.结论 NSCLC患者OS和PRS与多个因素密切相关,其中术后早期(≤24个月)发生复发/转移的患者预后较差;复发/转移后治疗可以显著改善患者的OS与PRS.     

110例局部非小细胞肺癌手术治疗的预后分析

目的:探讨手术治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）患者的临床病理特征与预后的关系。方法:回顾分析110例NSCLC患者的临床资料,临床病理特征和治疗情况,并用Kaplan-Meier法进行预后分析。结果:110例NSCLC患者,男女比例为2.79∶1;年龄31~84岁,中位年龄63岁,＜65岁的61例,≥65岁的49例。中位生存时间为67个月。单因素分析结果显示,老年（P=0.026）、淋巴结转移阳性（P=0.049）及Ⅲ期患者（P=0.000）预后差。多因素分析结果显示年龄（P=0.014）及临床分期（P=0.001）是影响NSCLC患者生存的独立预后因素。亚组分析结果显示淋巴结转移阳性的NSCLC患者中,肿瘤位于右肺（P=0.005）及肿瘤最大径＞5 cm组（P=0.014）预后较差。结论:老年、临床分期为Ⅲ期、有淋巴结转移且肿瘤位于右肺及直径大于5 cm的患者预后差。     

非小细胞肺癌中Id蛋白的表达及预后意义

目的：研究4种分化抑制因子（inhibitors of differentiation,Id）Id1,Id2,Id3和Id4在非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中的表达及临床意义.方法：采用免疫组织化学方法检测68例非小细胞肺癌及对应癌旁肺组织中4种Id蛋白的表达水平并探讨其与NSCLC患者临床参数及生存时间的关系.结果：68例非小细胞肺癌中4种Id蛋白表达的阳性率分别为67.4％,89.7％,88.2％和64.7％,高于癌旁组织中的表达（P ＜0.05）;Id1和Id3蛋白与分化程度相关（P＜0.05）,Id2蛋白的表达与患者淋巴结转移正相关（P＜0.05）,4种Id蛋白的表达水平与患者的性别,年龄,组织类型及临床分期无关（P＞0.05）;Id2蛋白阴性与阳性表达的患者术后生存时间具有显著性差异（P＜0.05）.结论：4种Id蛋白在非小细胞肺癌患者中表达上调,Id1和Id3与NSCLC的分化程度相关,Id2蛋白与NSCLC的转移及患者的预后相关,可能作为评价其预后的标志.     

Role of pemetrexed in non-small cell lung cancer

Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells.     

非小细胞肺癌中基质金属蛋白酶-13表达及与预后的关系研究

Objective: To investigate the expression of MMP-13 in non-small cell lung cancer (NSCLC), so as to analyze its correlation with prognosis of NSCLC. Methods: MMP-13 expression was detected in 99 NSCLC tissues and 32 normal lung tissues by immunohistochemical method. Results: (1) Expression of MMP-13 (51.5%, 51/99) in cancer tissues was significantly higher than that in normal tissues 0% (P ＜ 0.05). Expression level of MMP-13 was significantly related to lymph node metastasis and clinical stage (P＜0.01). (2) Kaplan-Meier analysis showed that expression level of MMP-13 was closely correlate with the prognosis of NSCLC. Multivariate Cox model analysis suggested that the survival time was significantly related to clinical stage and the expression of MMP-13. Conclusion: MMP-13 is an independent factor that affect prognosis.     

Expression of MMP-13 and its correlation with prognosis in non-small cell-lung cancer

Objective： To investigate the expression of MMP-13 in non-small cell lung cancer （NSCLC）, so as to analyze its correlation with prognosis of NSCLC. Methods： MMP-13 expression was detected in 99 NSCLC tissues and 32 normal lung tissues by immunohistochemical method. Results： （1） Expression of MMP-13 （51.5%, 51/99） in cancer tissues was significantly higher than that in normal tissues 0% （P 〈 0.05）. Expression level of MMP-13 was significantly related to lymph node metastasis and clinical stage （P 〈 0.01）. （2） Kaplan-Meier analysis showed that expression level of MMP-13 was closely cor- relate with the prognosis of NSCLC. Multivariate Cox model analysis suggested that the survival time was significantly related to clinical stage and the expression of MMP-13. Conclusion： MMP-13 is an independent factor that affect prognosis.     

Infiltrating immune cells,but not tumour cells,express FasL in non-small cell lung cancer: No association with prognosis identified in 3-year follow-up

Non-small cell lung cancer (NSCLC) remains a difficult disease to treat and independent prognostic markers other than tumour stage and histology have not emerged. The immune cell content of solid tumours has been associated with tumour regression and at times, tumour progression. The involvement of immune cells in prognosis of NSCLC is poorly described. Poor immune responses within solid tumours have been linked with tumour production of immunosuppressive cytokines. Tumour expression of FasL is thought to disarm responses through the transduction of a death signal in Fas-expressing T cells. The existence of the 'tumour counterattack' in vivo has been questioned. We undertook to measure T cell and macrophage infiltration of the tumour bed in NSCLC and report the association between immune cell content and prognosis in a limited, 3-year analysis of survival (n = 113). In addition we investigated FasL expression (n = 45). T cells and macrophages were found to frequently infiltrate lung tumours, albeit in small numbers. Generally there were more T cells infiltrating than macrophages. T cell and macrophage numbers were not associated with prognosis. Lung tumours were found not to express FasL, although occasional immune cells surrounding tumour cells were strongly positive. FasL expression was not associated with prognosis in this series. Thus, immune cells infiltrating NSCLC are not capable of suppressing tumour growth, nor are they associated with tumour progression. We report that lung tumours do not express the FasL, and that although some immune cells are FasL positive, this is not a reflection of general immune cell activation.     

Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its prognostic significance in resected non-small cell lung cancer

BACKGROUND AND OBJECTIVES: Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of metalloproteinases that play important roles in development and progression of malignant tumors. We conducted a retrospective study of TIMP-3 expression in resected non-small cell lung cancer (NSCLC). METHODS: TIMP-3 expression was examined immunohistochemically in primary tumor specimens from 143 patients who underwent complete resection for NSCLC. Correlations between TIMP-3 expression grade and tumor histology, TNM classification, MMP-2 and MMP-9 expression grade, VEGF expression grade, intra-tumoral microvessel density, proliferative index, apoptosis index, and prognosis were analyzed. RESULTS: TIMP-3 expression was low in 40, moderate in 71, and high in 32 patients. Higher TIMP-3 expression was seen in squamous cell carcinoma than in adenocarcinoma (P = 0.001), and reduced TIMP-3 expression was significantly associated with nodal involvement (P = 0.016) and advanced pathologic stage (P = 0.036). MMP-2 expression was reduced along with enhanced TIMP-3 expression (P = 0.010). The 5-year overall survival rates of low, moderate, and high TIMP-3 patients were 53, 64, and 84%, respectively (P = 0.037). Multivariate analysis confirmed that enhanced TIMP-3 expression was an independent factor for a favorable prognosis (P = 0.037). CONCLUSIONS: TIMP-3 expression status was significantly correlated with pathologic stage and nodal involvement, and was an independent prognostic factor in resected NSCLC.     

SELDI-TOF-MS技术在非小细胞肺癌中的应用

表面增强激光解析离子化飞行时间质谱（SELDI-TOF-MS）技术是一种使用特殊的增强表面直接捕获待测样本中的蛋白质分子,然后经激光解析离子化．飞行时间质谱测定被捕获的蛋白质的相对分子量、丰度的新兴技术。目前该项技术已经成功应用于前列腺癌的诊断、子宫良恶性肿瘤的鉴别等方面。SELDI-TOF-MS技术通过寻找肿瘤病人相关的特异性蛋白用于对非小细胞肺癌的早期诊断,指导治疗及预测预后等方面具有很好的应用前景。     

153例经外科干预的非小细胞肺癌伴胸膜播散患者的预后研究

  目的  探讨经不同外科治疗方式干预的非小细胞肺癌（non-small cell lung cancer,NSCLC）伴胸膜播散患者的预后。  方法  回顾性分析2002年5月至2011年5月153例在中国医学科学院肿瘤医院胸外科接受外科手术并于术中或术后确诊NSCLC伴胸膜播散患者的临床资料。  结果  全组患者,3年和5年生存率分别为38.5%和24.2%,中位生存时间29.0个月。其中31例接受胸膜结节活检术,122例接受原发肿瘤切除术,两组患者5年生存率分别是16.1%和26.2%,中位总生存时间分别为24.0个和29.0个月,两组间生存差异均无统计学意义（P>0.05）。122例接受原发肿瘤切除术患者中,是否行淋巴结清扫和转移结节切除,以及行部分肺叶或肺叶切除对患者预后影响无显著性差异（P>0.05）。  结论  NSCLC伴胸膜播散患者预后较差,行不同外科干预方式生存未显示出显著性差异,外科干预的主要作用是除外及证实胸膜播散以明确病理诊断,指导后续治疗,肿瘤切除应慎重,其意义有待进一步探讨。