Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients’ clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.     

High Sam68 expression predicts poor prognosis in non-small cell lung cancer

Background

The nuclear protein Sam68 has been implicated in the oncogenesis and tumor growth. The aim of this study was to explore the clinical value of Sam68 in patients with non-small cell lung cancer (NSCLC).

Methods

We examined Sam68 expression in 50 NSCLC tissues and matched adjacent noncancerous tissues by quantitative RT-PCR (qRT-PCR) and Western blotting. Furthermore, the Sam68 protein expression was analyzed by immunohistochemistry in 208 NSCLC samples. Kaplan–Meier method and multivariate Cox regression model were used to evaluate the prognostic value of nuclear Sam68 expression in NSCLC for disease survival.

Results

The expression of Sam68 was significantly elevated in NSCLC tissues as compared with adjacent non-cancerous tissues (P < 0.01). The high expression of Sam68 in NSCLC was significantly correlated with lymph node metastasis and tumor TNM stage. Kaplan–Meier survival analysis revealed that high expression of Sam68 correlated with poor prognosis of NSCLC patients (P < 0.01). Multivariate analysis showed that Sam68 expression was an independent prognostic marker for overall survival of NSCLC patients (HR 2.73, 95 % CI 1.549–4.315, P = 0.002).

Conclusion

Our results suggest that high Sam68 expression predicts poor prognosis of NSCLC patients, and Sam68 may be potentially a prognostic biomarker for NSCLC.     

Long-term survival in three patients with metastatic non-small cell lung cancer treated with gefitinib

Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), produces radiographic regression and symptom relief in patients with refractory advanced non-small cell lung cancer. However, it remains controversial whether gefitinib improves patient survival. We report three cases of refractory metastatic non-small cell lung cancer who have survived approximately 3 years since they first started gefitinib. These long-term survivors were Japanese female non-smokers with adenocarcinoma, who often had multiple lung metastases and were effectively re-treated with gefitinib. One patient had a surgical specimen available for DNA extraction and showed deletions in exon 19 of EGFR. Our experience suggests that gefitinib may improve long-term survival in selected patients. Further studies are required to identify biomarkers downstream of the EGFR mutations that are involved in multiple lung metastases and which could identify those patients who may benefit from gefitinib re-treatment.     

Elevated RABEX-5 expression predicts poor prognosis in non-small-cell lung cancer

RABEX-5 has been studied in various solid tumors, but its role in non-small-cell lung cancer (NSCLC) remains unknown. This study is aimed to investigate the expression, the potential relevance to clinicopathological characters and prognostic significance of RABEX-5 in patients with NSCLC. A total of 120 NSCLC patients who underwent radical surgery between 2005 and 2010 were enrolled in the study. The clinicopathological data and survival time were reviewed. The mRNA and protein expression of RABEX-5 from the paired tumor specimens and adjacent normal tissues were determined, and its relationship with clinicopathological variables and prognosis was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of RABEX-5 for NSCLC. We found the mRNA and protein expression levels of RABEX-5 were significantly elevated in NSCLC tissues. The increased RABEX-5 expression was correlated strongly with tumor recurrence (P=0.005). The 5-year median OS and DFS were significantly shorter in the higher RABEX-5 expression group compared to that in the lower RABEX-5 expression group. Multivariate Cox analysis indicated that high RABEX-5 expression was an independent prognostic factor for OS and DFS (P<0.001). This data suggests that RABEX-5 is a potentially useful indicator for a poor prognosis for NSCLC.     

吉非替尼对晚期非小细胞肺癌患者生活质量的改善

Objective  

The aim of this study was to evaluate the effect of gefitinib on improvement of quality of life (QoL) of patients with advanced non-small cell lung cancer (NSCLC).     

晚期非小细胞肺癌恶性胸腔积液IL-6水平与EGFR-TKIs治疗疗效及预后的关系

目的:探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)恶性胸腔积液中白介素-6(interleukin-6,IL-6)与接受表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)治疗的疗效和预后的关系。方法:回顾性分析2014年01月至2017年05月在我院呼吸内科病理确诊NSCLC恶性胸腔积液73例患者的临床资料,采用流式荧光法检测胸腔积液中IL-6水平,蛋白磷酸化流式分析技术检测外周血单个核细胞中pSTAT1和pSTAT3表达,通过Kaplan-Meier法构建生存曲线,Cox比例风险模型行多因素分析。结果:整体入组患者的客观缓解率为64.4%,高IL-6组17例客观缓解率为41.2%,低IL-6组56例客观缓解率为71.5%,低IL-6组客观缓解率优于高IL-6组(P=0.006),所有完全缓解患者均为低IL-6组。高IL-6组和低IL-6组治疗失败时间(time to treatment failure,TTF)和总生存期(overall survival,OS)比较结果分别为:6.8个月 vs 10.5个月(P＜0.000 1),20.5个月 vs 26.4个月(P=0.000 3)。多因素回归分析示IL-6水平是影响TTF(P＜0.001,OR 6.190,95%CI 3.136~12.221)和OS(P＜0.001,OR 6.288 95%CI 3.060~12.925)的预后因素。在CD4+T淋巴细胞中,高IL-6组pSTAT1表达低于低IL-6组（P＜0.001）,两组间pSTAT3表达均无明显差异。结论:恶性胸腔积液中IL-6水平可能是预测EGFR敏感突变型NSCLC接受EGFR-TKIs治疗的患者临床预后的有效指标。     

Reduced expression of thrombospondin-1 correlates with a poor prognosis in patients with non-small cell lung cancer

Thorombospondin-1 (TSP-1) is a 450 kDa extracellular matrix glycoprotein, with anti-angiogenic activity. We analyzed the relationship in TSP-1 expression and Microvessel count (MVC), and also clinical factors, using immunohistochemical methods for non-small cell cancer (NSCLC). Histopathologically, there was inverse correlation between TSP-1 expression and MVC for squamous cell carcinoma, but not for adenocarcinoma cases. Among 199 completely resected cases of NSCLC, the 5-year survival was 77.0% when the expression of TSP-1 was maintained and 55.1% when the expression were reduced, respectively (P=0.0046). When compared with TSP-1 expression in the high MVC subgroup, there was significantly shorter survival time when TSP-1 expression was reduced (P=0.0091), and no significant difference was seen for the low MVC subgroup. Multivariate analysis revealed that expression of TSP-1 is as a prognostic factor of NSCLC. Our present data suggest that TSP-1 might not be a direct anti-angiogenic factor and the TSP-1 expression is a prognostic indicator of NSCLC.     

Prolonged survival of gefitinib treatment in patients with advanced and previously treated non-small cell lung cancer

The purpose of this study was to evaluate the survival outcome in patients with advanced and previously treated non-small cell lung cancer given gefitinib (GEF) at our institution. We reviewed the clinical records of 70 Japanese patients,among whom 33 received several chemotherapy treatment modalities including GEF monotherapy (GEF group), and the other 37 were given several chemotherapy treatment modalities without GEF monotherapy (non-GEF group). The median survival time (MST) after second-line chemotherapy in the GEF group was 527 days with 1-year and 2-year survival rates of 59% and 26%, respectively. The MST in the non-GEF group was 175 days with 1-year and 2-year survival rates of 21% and 16%, respectively. Overall survival after second-line chemotherapy in the GEF group was significantly longer than in the non-GEF group (hazard ratio 1.93; 95% confidence interval 1.15-3.53, p=0.014). In our limited clinical experience, chemotherapy treatment including GEF monotherapy appeared to have longer survival than non-GEF treatment.     

Pretreatment serum C-reactive protein level predicts poor prognosis in patients with hepatocellular carcinoma

C-reactive protein (CRP) is known to be associated with poor prognosis in patients with various malignancies. We investigated the relationship between the pretreatment serum CRP level and survival in patients with hepatocellular carcinoma (HCC) in various stages of the disease. A cohort of 133 patients with newly diagnosed HCC was prospectively evaluated. The patients were divided into two groups: high-CRP group (n?=?27) with the pretreatment serum CRP level?≧?1.0?mg/dl and low-CRP group (n?=?106) with the CRP level?相似文献   

MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer

Matrix metalloproteinase-14 (MMP-14) has been demonstrated to play an important role in tumor progression. The aim of this study was to analyze the correlation between MMP-14 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). Immunohistochemical staining for MMP-14 protein was performed in 104 patients with NSCLC. High levels of MMP-14 protein were positively correlated with the status of clinical stage (I–II vs. III–IV; P?P?P?=?0.014), and differentiated degree (high vs. low or undifferentiated; P?=?0.001). The patients with higher MMP-14 expression of protein had shorter survival time than patients with low MMP-14 expression. Multivariate analysis indicated that the level of MMP-14 expression was an independent prognostic indicator (P?NSCLC. In conclusion, MMP-14 is a potential unfavorable prognostic factor for patients with NSCLC.     

MCAM expression is associated with poor prognosis in non-small cell lung cancer

Background

MCAM has been recently identified as a biomarker for epithelial–mesenchymal transition (EMT) and is potentially involved in metastasis of cancer. The current study aimed at investigating the expression of MCAM in non-small-cell lung cancer (NSCLC) and its clinico-pathological significance.

Methods

A follow-up analysis was performed on 118 patients with NSCLC resected by lobectomy or pneumectomy with systematic lymph node dissection. All patients were followed for 6–60 months. Immunostaining of tissue sections from primary tumors and their lymph node metastasis was performed and evaluated using monoclonal antibody against MCAM, E-cadherin, and vimentin. Correlations were investigated between MCAM immunostaining in primary tumors and E-cadherin, vimentin immunostaining, lymph node metastasis, and survival.

Results

MCAM protein expression was found in 46.61 % of squamous cell carcinomas and 37.47 % of adenocarcinomas; MCAM expression positively correlated with vimentin, but inversely with E-cadherin (both P values <0.05). There were significant correlations between the MCAM immunostaining score in primary tumors and in their lymph node metastasis (P = 0.03). According to the Kaplan–Meier survival estimate, the level of MCAM expression in primary tumors was a statistically significant prognostic factor (P < 0.05).

Conclusions

MCAM expression in surgically treated NSCLC is clearly associated with lymph node metastasis and poor prognosis.