晚期小细胞肺癌和非小细胞肺癌不同转移部位预后意义的比较

  目的  明确不同转移部位对小细胞肺癌（small cell lung cancer,SCLC）和非小细胞肺癌（non-small cell lung cancer,NSCLC）预后影响的差异。  方法  回顾性分析天津医科大学肿瘤医院2012年1月至2017年12月确诊为晚期SCLC 266例和2015年1月至2017年12月确诊为晚期NSCLC 275例,总计541例患者病例资料。主要观察指标为总生存期（overall survival,OS）。  结果  在SCLC中,与多器官转移者相比,单器官转移者的预后更好（P=0.000 4）;在NSCLC中,单器官与多器官转移者之间未见到明显的生存差异（P=0.451）。在SCLC单器官转移者中,脑转移的预后相对最好,骨转移的预后相对较差,肝转移的预后最差,三者的中位生存时间（median survival time,MST）分别为14.5、11.5和10.3个月;在NSCLC单器官转移者中,肺内转移的预后最佳,肝和肾上腺转移者的预后较差,三者的MST分别为未达到、7.6和7.3个月。在SCLC多器官转移者中,有骨（P=0.046）、肝（P=0.019）转移者预后较差;而有无脑（P=0.995）、肺（P=0.847）、肾上腺（P=0.255）转移对患者的预后无显著性影响;在NSCLC多器官转移的患者中,有脑（P=0.054）、肾上腺转移（P=0.006）的患者预后较差;有肺（P=0.008）转移的患者预后较好;而有无骨（P=0.091）、肝（P=0.300）转移对患者的预后无显著性影响。  结论  不同转移部位对SCLC和NSCLC预后的影响存在差异。      

The prognostic effects of hyponatremia and hyperchloremia on postoperative NSCLC patients

Electrolytic disorders are common in lung cancer patients. But the association between serum electrolytes levels and survival in patients undergoing lung cancer resections for non–small-cell lung cancer (NSCLC) has been poorly investigated. A retrospective study was conducted on consecutive postoperative NSCLC patients. Pearson's test was used to determine the association between serum sodium and chlorine levels and clinical characteristics, and cox regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. We found that hyponatremia was an independent prognostic factor associated with poor prognosis in NSCLC patients undergoing complete resection (log-rank test, P = 0.004). In addition, we found that hyperchloremia predicted a poor clinical outcome in patients with non-anion-gap (log-rank test, P = 0.011), whereas it predicted a favorable clinical outcome in patients with high-anion-gap (log-rank test, P = 0.002). The serum electrolytes levels may reflect the prognosis of NSCLC patients who receive complete resection. Early detection, monitoring, and management of hyperchloremia and hyponatremia might improve patients’ prognosis.     

Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer

High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1-3, N0-2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P= 0.009 and P= 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r= 0.21; P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P < 0.02) and microvessel density (P < 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC.     

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.     

Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer

High expression levels of TrkB and BDNF are associated with aggressive malignant behavior in tumor cells and a poor prognosis in patients with various types of cancer. In this study, we aimed to identify the relationship between TrkB and BDNF expression and clinicopathological variables and prognosis in non-small cell lung cancer (NSCLC). We evaluated TrkB and BDNF expression in the tumor cells of 102 NSCLC patients by immunohistochemistry. Out of all clinicopathological factors examined, only vascular invasion was significantly correlated with TrkB (P=0.010) and BDNF (P=0.015) expression. TrkB-positive tumors had significantly worse disease-free survival (P=0.0094) and overall survival (P=0.0019) than TrkB-negative tumors, and TrkB expression was an independent prognostic factor for disease-free survival (HR 3.735, 95%C.I. 1.560-11.068, P=0.002) and overall survival (HR 4.335, 95%C.I. 1.534-15.963, P=0.004) in multivariate analysis. Finally, our analysis revealed that co-expression of TrkB and BDNF conferred poorer prognosis compared with overexpression of either protein alone. Our results indicate that expression of TrkB and BDNF is associated with poor prognosis in NSCLC patients.     

Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer.

PURPOSE: Estrogen receptor-alpha (ER-alpha) and -beta (ER-beta) play important roles in the carcinogenesis of breast tumors. Similarly, there have been several reports of ER expression in lung cancers, but the results have not been consistent, and the receptors' prognostic value remains unclear. Our goal was to investigate ER expression in non-small cell lung cancer (NSCLC) and to assess whether their expression correlates with prognosis. EXPERIMENTAL DESIGN: ER expression was examined using immunohistochemical methods with sections from 132 resected NSCLC specimens. Kaplan-Meier survival curves were analyzed to determine the significance of ER expression in the prognosis of NSCLC patients. RESULTS: ER-alpha was detected in the cytoplasm of 73% of the specimens analyzed, whereas ER-beta was detected in the nucleus of 51%. ER-alpha expression correlated with poorer overall survival (P < 0.001), as did the absence of ER-beta expression (P = 0.048). Likewise, at histopathologic stage I, ER-alpha expression (P = 0.028) or the absence of ER-beta (P = 0.037) correlated with a poorer prognosis, and ER-alpha(+)ER-beta(-) patients had a significantly worse prognosis than ER-alpha(-)ER-beta(+) patients (P = 0.00007). Multivariate Cox regression analysis revealed the absence of ER-beta to be an independent factor predictive of poor disease outcome (hazard ratio, 1.9; 95% confidence interval, 1.1-3.4; P = 0.0264). CONCLUSIONS: ER-alpha expression and the absence of ER-beta expression are associated with a poorer prognosis among NSCLC patients. In particular, the absence of ER-beta could serve as a marker identifying patients at high risk even at an early clinical stage.     

MTA1表达与中国肺癌患者预后关系的meta分析

背景与目的 已有的研究表明:在多种恶性肿瘤中发现转移相关蛋白1(metastasis associated protein 1, MTA1)发挥着促进肿瘤侵袭与转移的作用,且与肿瘤患者预后不佳有关.目前MTA1在肺癌中的预后作用仍有争议,故我们采用meta分析的方法评估其在肺癌患者中的预后价值.方法 通过计算机检索PubMed、Embase、万方数据库、中国生物医学文献数据库、中国知网等数据库,收集纳入研究MTA1表达与肺癌预后关系的文献及相关数据,采用Stata 12.0软件进行数据分析,合并值为风险比(hazard ratio, HR).结果 总共纳入8项研究共712例中国肺癌患者,对这些研究进行异质性检验,发现存在异质性(I2=59.0%,P=0.017),故采用随机效应模型进行数据合并得HR=2.07(95%CI: 1.42-3.02, P<0.001).同时分层分析显示在非小细胞肺癌(non-small cell lung can-cer,NSCLC)中各研究无明显异质性(I2=47.0%,P=0.093),采用固定效应模型合并得HR=1.66(95%CI:1.27-2.18, P<0.001).结论 MTA1高表达可能是中国NSCLC患者预后不良的一个指标,在肺癌及小细胞肺癌中的预后价值尚缺乏证据.     

Increased expression of collagen XVIII and its prognostic value in nonsmall cell lung carcinoma

BACKGROUND: Angiogenesis plays a crucial role in tumor growth and metastasis. Recently, some studies have focused on the angiogenesis inhibitor endostatin. However, the biologic role of the precursor of endostatin, collagen XVIII, in human malignancy is unknown. The purpose of the current study was to evaluate whether the expression of collagen XVIII has additional prognostic value for survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The authors investigated the expression of collagen XVIII in 221 patients using immunohistochemical methods. To confirm the specificity of the collagen XVIII polyclonal antibody used in the current study and to test the expression of collagen XVIII in human lung carcinoma, Western blot analysis was performed on a panel of human lung carcinoma cell lines. RESULTS: Collagen XVIII expression was detected in 162 of 221 patients with NSCLC (73%), primarily in the tumor cell cytoplasm. Low collagen XVIII expression levels were found in 75 tumor specimens, while high collagen XVIII expression levels were noted in 87 tumor specimens. The prevalence of positive collagen XVIII expression was greater in T2-4 tumors than in T1 tumors (P = 0.0235). The prognosis for patients with strongly collagen XVIII-positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII-positive or collagen XVIII-negative NSCLC (P = 0.0010). Multivariate analysis indicated that T status, lymph node status, and the overexpression of collagen XVIII were independent prognostic factors. CONCLUSIONS: The results of the current study indicated that the overexpression of collagen XVIII was associated with NSCLC progression and poor outcome. Thus, collagen XVIII expression may serve as a useful prognostic marker in patients with NSCLC.     

Prognostic value of circulating chromogranin A and soluble tumor necrosis factor receptors in advanced nonsmall cell lung cancer

BACKGROUND: Increased levels of chromogranin A (CgA), a protein secreted by many neuroendocrine cells, have been detected in sera of patients with neuroendocrine tumors or renal, hepatic, or heart failure. In patients with heart failure, serum CgA correlates with tumor necrosis factor-alpha (TNF) and soluble TNF receptors (sTNF-Rs), with important prognostic implications. The prognostic value of CgA and sTNF-Rs was investigated in advanced nonsmall cell lung cancer (NSCLC), a histologically heterogeneous group of tumors that may undergo neuroendocrine differentiation. METHODS: CgA and sTNF-Rs were analyzed in the sera of 88 patients with NSCLC before chemotherapy by enzyme-linked immunoadsorbent assay (ELISA) and in tumors by immunohistochemistry. RESULTS: Thirteen percent of patients had CgA values greater than the highest value observed in normal subjects (distribution range, 9-724 ng/mL and 28-196 ng/mL, respectively). Immunohistochemical studies showed no correlation between CgA expression in tumors and serum levels. Conversely, circulating CgA was associated with worse Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P = .0005), more advanced stage (P = .042), and survival, with CgA being an independent prognostic factor of poor outcome (hazards ratio [HR] 1.31 for 100 ng/mL increase; 95% confidence interval [95% CI], 1.08-1.60 [P = .0071]). sTNF-R1 and sTNF-R2 were also associated with ECOG PS (P = .0001 and P = .02, respectively). sTNF-Rs was weakly correlated with circulating CgA (r = 0.39 for TNF-R1 and r = 0.40 for TNF-R2), suggesting a regulatory link between sTNF-Rs and CgA secretion. CONCLUSIONS: Increased serum levels of CgA in NSCLC are independent from protein expression in tumors and more likely related to neuroendocrine response associated with worsening of patient condition. In addition to ECOG PS and stage, CgA is an independent indicator of poor prognosis.     

RASSF4的异常表达在非小细胞肺癌中的意义

目的:探讨RASSF4在非小细胞肺癌中的表达模式和意义。方法:应用免疫组化及Western Blot方法,检测并分析89例非小细胞肺癌样本中RASSF4的表达情况及其与临床病理因素的相关性。结果:在非小细胞肺癌组织中,41.57%（37/89）出现RASSF4的表达下调,并且其异常表达与患者的高TNM分期(P=0.005)、淋巴结转移(P=0.024)及患者不良预后(P=0.018)相关。在肺癌细胞系中,我们在部分细胞系（57.14%,4/7）中发现了RASSF4的异常表达。结论:RASSF4蛋白的弱表达可能是判断非小细胞肺癌恶性程度的重要标志之一。     

Intratumoral lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region

Head and neck squamous cell carcinomas (HNSCCs) frequently disseminate to regional lymph nodes. To investigate the possible mechanisms involved, we studied the expression of cancer cell adhesion molecules together with lymphatic vascular and blood vascular markers in a panel of 97 primary HNSCC tumors and correlated expression levels with conventional clinicopathological parameters and with long-term prognosis. In particular, we measured the density of intratumoral and peritumoral lymph vessels as assessed with the marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and the density of tumor CD44, a receptor up-regulated in many metastatic cancers. Intratumoral LYVE-1(+) lymphatic vessels were clearly associated with a higher risk for local relapse as well as with poor disease-specific prognosis (P = 0.02 and 0.0009, respectively). In contrast, a high density of peritumoral LYVE-1(+) vessels was a sign of favorable survival (P = 0.05). Strong primary tumor CD44 expression was associated with a poor prognosis, an increased risk of local recurrence (P = 0.03 and 0.02, respectively), and an increase in resistance to radiation therapy (P = 0.03). CD44 was the only factor with an independent prognostic value for the disease-specific overall survival (P = 0.04). Our results suggest that intratumoral lymphatics play a greater role than peritumoral lymphatics in nodal metastasis of HNSCC and that tumor CD44 levels can predict sensitivity to radiation therapy. These parameters may be useful predictive and prognostic tools in the clinical management of HNSCC.     

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。     

Absence of correlation between nuclear morphometry and survival in stage I non-small cell lung carcinoma.

To evaluate the utility of nuclear morphometry as a prognostic indicator in lung cancer, 5-year follow-up information was obtained in 46 cases of surgically resected Stage I non-small cell lung cancer (NSCLC). Nuclear area, perimeter, major diameter, minor diameter, and nuclear shape factor were determined from representative histologic sections of the tumors with a computer-assisted digitizing system. The morphometric parameters were compared between patients with favorable outcome (Group I: alive with no evidence of disease, n = 17) and those with poor outcome (Group II: dead of disease or with recurrence of disease, n = 29). No significant differences in any of the morphometric parameters were found between tumors in Groups I and II for individual tumor cell types or the combined cases. Failure to demonstrate a correlation between morphometric parameters and prognosis in Stage I NSCLC indicates that future efforts to determine objective prognostic factors should concentrate on other variables, such as specific genetic abnormalities.     

Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis

Akt, a downstream mediator of phosphatidylinositol 3-kinase (PI3K), is a signal transduction protein that plays a central role in tumorigenesis. The tumor suppressor gene PTEN negatively regulates the PI3K/Akt signaling pathway. However, the roles of Akt and PTEN function in patients with non-small cell lung cancer (NSCLC) is not well established. To clarify roles of expression of phosphorylated Akt (p-Akt) and loss of PTEN expression in biological behavior and prognosis of NSCLC. Immunohistochemical staining was used to determine the expression of p-Akt and PTEN in 20 cases of normal lung tissues and 102 cases patients with NSCLC. All patients with NSCLC were followed from 3 to 60 months. The positive incidence of p-Akt expression and loss incidence of PTEN expression in NSCLC were 41.2% (42/102) and 46.1% (47/102), while negative of p-Akt expression (0%, 0/20) and positive of PTEN expression (100%, 20/20) in normal lung tissues. Overexpression of p-Akt and loss of PTEN expression were correlated to poor differentiation, lymph node involvement, distant metastasis and late stages. A significant negative correlation was observed between expression of p-Akt and PTEN (r = -0.425, P < 0.001). Patients with p-Akt positive expression (42/102) and loss of PTEN expression (47/102) showed significantly worse 5 years survival rate and median survival time than relevant those with p-Akt negative expression (14.29% versus 33.33%, 14 months versus 32 months, Log-rank test X(2) = 14.24, P < 0.001) and PTEN positive expression (10.64% versus 38.18%, 15 months versus 40 months, Log-rank test X(2) = 21.06, P < 0.001). A univariate analysis revealed that smoking, tumor size, lymph node involvement, distant metastasis, stage, p-Akt and loss of PTEN expression were significant correlative factors with prognosis. The result of multivariate Cox analysis showed that smoking, stage and loss of PTEN expression were independent prognosticators. p-Akt is overexpressed and accompanied by the loss of PTEN in clinical specimens of NSCLC. Both p-Akt and PTEN are concerned with invasion and metastasis of NSCLC. Loss of PTEN expression is an independent poor prognostic factor for patients with NSCLC.     

423例非小细胞肺癌患者生存的多因素分析

背景与目的:非小细胞肺癌在我国发病率高且预后较差,需要新的预后因子来指导对该病患者的治疗。本研究总结非小细胞肺癌完全切除术患者的临床特征和生存结果,探讨影响癌灶复发和转移的临床因素。方法:建立423例患者的病例资料库,采用SPSS10.0统计软件进行单因素和多因素生存分析。结果:本组病例5年生存率为46.98%,Cox分析显示独立的预后不良因素有TNM分期较晚(P=0.003)和B型血(B型与非B型,P=0.02),独立的良好预后因素有行辅助化疗(P=0.04)和病理类型为鳞癌(P=0.005);随着预后不良因素(非鳞癌和B型血)的增加,Ⅲa期患者5年生存率相应呈下降的趋势(43.5%vs23.7%vs4.0%,P<0.001)。结论:非小细胞肺癌患者完全切除术后辅助化疗对预后可能有益,联合分析病理类型和血型,可以提供Ⅲa期患者一个新的预后模式。     

Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features

The aim of this study was to investigate the prognostic significance of E-cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101 primary carcinomas were retrospectively studied. The level of E-cadherin expression was determined by immunohistochemistry. There was a significant correlation between decreased E-cadherin expression and the presence of nodal metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were also associated with nodal metastases. Multivariate analysis confirmed that these three parameters were independent predictors of nodal metastases. Decreased E-cadherin expression also correlated with an increase in recurrence rates (P=0.019). However, in multivariate analysis only pathological N-stage was significantly associated with disease-specific survival. We conclude that E-cadherin is an independent predictor of nodal metastases in supraglottic squamous cell carcinomas. Determination of E-cadherin expression levels might be useful in identifying patients with clinically negative lymph nodes who are at risk of occult metastases, allowing more effective treatment strategies to be implemented.     

Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases.

PURPOSE: The purpose is to identify biological markers that predict brain metastasis and treatment outcome in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Samples were obtained from the primary tumors, lymph nodes, and brain metastases of 29 patients with NSCLC who had undergone resection of both the pulmonary tumors and the brain lesions. Samples from 29 patients matched for age, sex, and histology whose pulmonary tumors were resected served as controls. Samples were stained with H&E as well as immunohistochemical stains for epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX-2), and BAX. Comparisons were made between patients with and without brain metastasis. Independent investigators determined the percentage of positive cells. RESULTS: There was positive correlation in expression of all three biomarkers between primary lung tumors and lymph node metastases. Significantly higher levels of EGFR were found in lymph node metastases in the control group (P = 0.0147). COX-2 expression in brain lesions correlated with expression in primary tumors (P = 0.023). BAX levels were lower in poorly differentiated tumors in lymph node metastases in the control group (P = 0.01) and in brain metastases (P = 0.045). Low EGFR expression and high COX-2 expression in lymph node metastasis were associated with poorer treatment outcome. CONCLUSIONS: Expression of EGFR, COX-2, and BAX in primary lung tumors did not differ between patients with brain metastases from NSCLC and those without brain metastases. These three biomarkers cannot be used to predict brain metastasis. Studies of other biomarkers are under way in an effort to predict brain metastasis among patients with NSCLC.     

TGF-β1 Protein Expression in Non-Small Cell Lung Cancers is Correlated with Prognosis

To investigate the expression intensity and prognostic significance of TGF-β1 protein in non-small celllung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normallung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-β1 protein expression insystematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-β1PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated withTNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history,tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated thatpatients with high TGF-β1 protein expression and lymph node metastases demonstrated a poor prognosis (bothp=0.000, ). Multivariate analysis showed that TGF-β1 protein expression (RR = 2.565, p=0.002) and lymph nodemetastases (RR=1.874, p= 0.030) were also independent prognostic factors. Thus, TGF-β1 protein expressionmay be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.     

Prognostic value of smoking status in operated non-small cell lung cancer

Despite the indisputable link between smoking and the increased risk for lung cancer, the inclusion of this factor in prognostic survival analysis has been scarce. Important clinical questions regarding the smoking status are the basis of this study and are as follow: what is the prognostic benefit of having been a non-smoker or having stopped smoking prior to developing lung cancer and what is the prognostic benefit of smoking cessation at the time of diagnosis of lung cancer? Cigarette smoking status of 311 patients operated for non-small cell lung cancer (NSCLC) by a single surgeon was determined based on two independent questionnaires taken prospectively prior to lung operation. Of all patients analysed, 169 (54.3%) were current smokers, 25 (8.0%) were non-smokers, 82 (26.4%) were former smokers and 35 (11.3%) were recent quitters. A Cox multiple regression model was used to test the prognostic value of smoking status on survival together with other relevant clinicopathological factors. For overall survival, older age (P = 0.011), presence of lymph node metastases (P < 0.001) and current smoking (P = 0.001) were independent predictors of poor prognosis, while non-smokers (relative risk = 0.447, 95% confidence interval = 0.206-0.970, P = 0.042), former smokers (relative risk = 0.543, 95% confidence interval = 0.350-0.843, P = 0.006) and recent quitters (relative risk = 0.340, 95% confidence interval = 0.164-0.705, P = 0.004) had a significant better prognosis compared to current smokers (referent group). Similar results were obtained for disease-free survival. These results indicate that smoking cessation is beneficial for lung cancer patients at any time point prior to lung operation and current smoking at the time of operation is associated with poor prognosis.     

miR-21和PDCD4在非小细胞肺癌中的表达及其临床意义

目的:探讨微小核糖核酸21（miR-21）和程序性细胞死亡因子4（programmed cell death 4,PDCD4）在非小细胞肺癌(NSCLC)组织中的表达及临床意义。方法:应用Real-time PCR法检测61例NSCLC组织及61例对应癌旁肺组织中miR-21、PDCD4的表达,分析二者表达的相关性及其与临床病理特征和预后的关系。结果:同癌旁正常组织相比,NSCLC组织中miR-21 mRNA表达明显上调（88.52%,P=0.000）,PDCD4 mRNA表达明显下调（83.61%,P=0.000）。两者表达呈负相关（r＝0．044,P＜0.05）。中晚期（Ⅲ-Ⅳ期）肺癌组织中miR-21 mRNA表达高于早期（Ⅰ-Ⅱ期）（P＜0.05）。PDCD4 mRNA 表达与NSCLC的分化程度、临床分期及淋巴转移相关（P＜0.05）。Kaplan-Meier 生存分析显示miR-21高表达患者较低表达患者总生存期明显缩短（P=0.007）,相反,PDCD4高表达的患者较低表达患者具有较长的总生存期(P=0.003)。