骨桥蛋白预测早期非小细胞肺癌患者预后的意义

目的 探讨骨桥蛋白（osteopontin,OPN）在非小细胞肺癌（non-small cell lung cancer,NSCLC）中的表达和预后意义。方法 采用免疫组织化学法检测84例非小细胞肺癌组织中OPN表达情况,利用χ 2检验和Kaplan-Meier生存曲线分析OPN表达与临床病理相关因素及患者术后总生存时间（overall survival,OS）、无疾病生存时间（disease-free survival,DFS）的关系。结果 84例非小细胞肺癌组织中OPN阳性表达率为83.3%（70/84）。在早期患者中,OPN阴性表达组DFS和OS长于OPN阳性组（χ ²=9.722,P=0.019;χ ²=6.064,P=0.014）。而晚期患者OPN阴性表达组DFS和OS与阳性组间比较差异无统计学意义。结论 非小细胞肺癌组织中存在OPN表达,OPN可能成为预测早期NSCLC患者预后的参考指标。     

整合素α7在非小细胞肺癌组织中的表达及临床意义

探讨整合素α7(ITGA7)在非小细胞肺癌(NSCLC)组织中的表达及与临床病理特征和预后的关系。方法回顾性分析2009年1月至2013年12月178例接受手术切除的NSCLC患者的临床病理资料。采用免疫组化SP法检测NSCLC和配对癌旁组织中ITGA7的表达水平。分析ITGA7表达与NSCLC临床病理特征以及无病生存期(DFS)和总生存期(OS)的关系。结果NSCLC组织中ITGA7的高表达率为38.2%(68/178),低表达率为61.8%(110/178);在癌旁组织中分别为23.0%(41/178)和77.0%(137/178)。ITGA7在NSCLC组织中的表达水平高于配对癌旁组织,差异有统计学意义(P=0.004)。ITGA7在NSCLC组织中的表达与分化程度和肿瘤直径有关(P<0.05),与年龄、性别、淋巴结转移和TNM分期无关(P>0.05)。NSCLC患者中,ITGA7高表达者的中位DFS为28.0(95%CI:21.7~34.3)个月,低于低表达者的35.0(95%CI:29.5~40.5)个月,差异有统计学意义(P=0.014);ITGA7高表达者中位OS为41.0(95%CI:30.5~51.5)个月,低于低表达患者的43.0(95%CI:31.9~54.1)个月,差异有统计学意义(P=0.040)。Cox多因素分析显示,ITGA7表达、分化程度和淋巴结转移是影响DFS的独立因素;分化程度和淋巴结转移是影响OS的独立因素。结论ITGA7在NSCLC组织中高表达,且与肿瘤低分化、肿瘤直径大以及不良预后有关。     

LncRNA-SChLAP1在结直肠癌组织中高表达的预后评估意义

目的 探讨长链非编码RNA-SChLAP1过表达对结直肠癌(CRC)预后的影响。方法 选取符合严格随访标准的156例CRC患者和 43例癌旁结直肠组织进行qRT-PCR检测,评估SChLAP1表达与CRC临床病理特征和总生存期(OS)、无病生存期(DFS)的关系,以及影响CRC患者OS和DFS的风险因素。结果 CRC中SChLAP1水平明显高于癌旁结直肠组织,差异有统计学意义(P＜ 0.01)。SChLAP1高表达与CRC的分化和分期有关,也与DFS和OS有关(P＜ 0.01)。Cox比例风险回归模型发现SChLAP1表达是CRC患者OS和DFS下降的独立风险因素。结论 SChLAP1在CRC进展中起着重要作用,SChLAP1 可能作为独立的生物标志物用于CRC的预后评估。     

High expression of CASK correlates with progression and poor prognosis of colorectal cancer

Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at cell–cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan-2, is involved in cell proliferation, cytoskeletal remodeling, and cell migration. To demonstrate the role of CASK in colorectal cancer (CRC) carcinogenesis, we examined the expression of CASK and its binding protein syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC specimens and the controls from adenomas and normal mucosae by immunohistochemical staining and Western blot analysis. Syndecan-2 protein level was tested in CRC samples and the controls by Western blot analysis. The correlations between CASK expression and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues. Furthermore, high expression of CASK and syndecan-2 was significantly correlated with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis showed that patients with low CASK staining had a significantly better survival compared to patients with high CASK staining. In multivariate analysis, CASK overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion, and liver metastasis were independent prognostic factors of poor DFS and OS. Our present study indicates that CASK overexpression is associated with an unfavorable prognosis. CASK is an independent prognostic factor for CRC, which suggests that it is a novel and crucial predictor for CRC metastasis.     

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.     

High expression of M3 muscarinic acetylcholine receptor is a novel biomarker of poor prognostic in patients with non-small cell lung cancer

We assessed the expression of M3 receptor in non-small cell lung cancer (NSCLC) and determined its relationship with clinicopathological features and its impact on patient outcome. Specimens from 192 patients with NSCLC were investigated by immunohistochemistry for M3 receptor and Ki67 expression. Correlation between the expression of M3 receptor and Ki67 and various clinicopathological features of NSCLC patients was analyzed. We found that M3 receptor expression was gradually elevated from normal to metaplasia/dysplasia tissues to cancer tissues. Furthermore, there was a similar trend for Ki67 expression. Statistical analysis revealed that M3 receptor expression in tumor cells were correlated significantly with stage (P?<?0.0001), histology type (P?=?0.0003), Ki67 expression (P?<?0.0001), tumor size (P?<?0.0001), lymph node status (P?<?0.0001), LVS invasion (P?=?0.0002), and histology grade (P?<?0.0001). Patients with M3 receptor high expression showed far lower disease-free survival (DFS) and overall survival (OS) rates than those with M3 receptor low expression. Multivariate Cox regression analysis demonstrated that high M3 receptor expression was an independent prognostic factor for both DFS and OS. High M3 receptor expression correlates with poor survival in NSCLC patients. M3 receptor expression may be related with tumor progression in NSCLC, indicating that M3 receptor may be a novel antineoplastic target in the future.     

Low Wilms' tumor gene expression in tumor tissues predicts poor prognosis in patients with non-small-cell lung cancer

We elucidated the relationship between prognosis of non-small-cell lung cancer (NSCLC) and Wilms' tumor gene (WT1) mRNA expression in tumor tissue. The WT1 mRNA expression levels of the fatal cases were lower as compared with those of the survival cases. Overall survival (OS) and disease-free survival (DFS) of the high WT1 expression group were longer than of the low expression group. As for squamous cell lung cancer (SQLC), low WT1 expression was significantly associated with lymph node metastasis. Cox analysis revealed that the gene level was a significant prognostic factor in OS and DFS. Low WT1 expression predicted poor prognosis in patients with NSCLC.     

Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic factor in resectable non-small cell lung cancer

Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) has been considered to be a tumor suppressor in human cancer, but its clinical and prognostic significance in non-small cell lung cancer (NSCLC) has not been well elucidated.A retrospective analysis of 215 patients with surgically resected NSCLCs from Sun Yat-Sen University Cancer Center between April 2002 and March 2005 was performed using immunohistochemistry and Western Blot to analyze PTPN12 expression. The association between PTPN12 expression and patient survival was investigated.Western Blots showed that the expression level of PTPN12 were higher in normal paracancerous lung tissues than in NSCLC tissues. High PTPN12 expression was less common in the presence than in the absence of visceral pleural invasion (p=0.038). Patients with PTPN12-high tumors had a longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (p<0.001), especially for those with non-squamous cell carcinoma (non-SCC) (DFS, p<0.001; OS, p<0.001). Multivariate analysis confirmed that PTPN12 positivity was associated with increased survival duration (DFS, p<0.001; OS, p<0.001), independent of prognostic indicator.High PTPN12 expressive levels are associated with favorable survival duration in patients with NSCLC, especially those with non-SCC. Our study suggests that PTPN12 expression is a valuable prognostic biomarker for NSCLC patients.     

Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer prognosis and therapeutics

Ubiquitin-specific protease 22 (USP22) exhibits an important function in tumor progression and oncogenesis. The aim of this study was to investigate the role of USP22 and the association with its potential targets in patients with cervical cancer. To our knowledge, this is the first study that determines the relationship between USP22 expression and clinicopathological significance in cervical cancer. The immunohistochemistry results showed that USP22 protein was overexpressed in cervical cancer samples compared with normal cervical tissues (P?<?0.001). Moreover, clinicopathological analysis showed that USP22 expression was highly related to International Federation of Gynecology and Obstetrics stage, Ki67, lymph node metastasis, and histology grade. The results of Kaplan–Meier analysis indicated that patients with high USP22 expression had significantly shorter overall survival (OS) and disease-free survival (DFS) than patients with low expression of USP22 (P?<?0.001). Multivariate Cox regression analysis revealed that USP22 expression status was an independent prognostic marker for both OS and DFS of patients with cervical cancer. It is suggested that USP22 overexpression may be associated with poor prognosis in cervical cancer. It may represent a novel prognostic biomarker or a target for improving the treatment efficiency of patients with cervical cancer.     

GCNT3表达在非小细胞肺癌中的临床意义

  目的  研究葡萄糖胺基转移酶3(glycosyltransferase enzyme 3, GCNT3)在非小细胞肺癌(non-small cell lung cancer, NSCLC)组织及对应正常组织中的表达情况, 探讨其表达水平与NSCLC患者临床病理特征、总生存期(overall survival, OS)和无进展生存期(progression-free survival, PFS)的关系。  方法  分别应用实时定量反转录链式反应(qRT-PCR)和蛋白质印记技术(Western blot, WB)检测GCNT3在2017年3月至2017年7月天津医科大学肿瘤医院20例NSCLC患者癌组织及对应的正常组织中的表达情况; 此外, 收集2010年1月至2014年12月本院164例NSCLC患者的石蜡组织标本, 通过免疫组织化学技术(immunohistochemistry, IHC)评估样本中GCNT3表达, 分析GCNT3表达水平与临床病理学特征之间的关系, 探究GCNT3表达与NSCLC患者OS及PFS的关系, 通过细胞功能实验研究GCNT3对NSCLC细胞增殖能力、侵袭能力和迁移能力的影响。  结果  qRT-PCR与WB结果均显示GCNT3在NSCLC癌组织中的表达水平明显高于正常组织。IHC结果显示GCNT3表达水平与NSCLC患者的性别、吸烟史、组织学类型、病理分期和淋巴结转移相关; Kaplan-Meier分析显示GCNT3高表达NSCLC患者OS和PFS均差于GCNT3低表达患者(P < 0.05)。多因素Cox比例风险回归模型分析显示, GCNT3表达是NSCLC患者预后的独立因素(P < 0.05)。抑制GCNT3表达后, NSCLC细胞的增殖能力、侵袭能力和迁移能力明显减弱(P < 0.05)。  结论  GCNT3在NSCLC癌组织中高表达, GCNT3高表达的NSCLC患者OS和PFS较差, GCNT3有望成为评估NSCLC患者预后的标志物。      

探讨Tim-3在非小细胞肺癌浸润巨噬细胞上的表达及其对预后的影响

背景与目的：T细胞免疫球蛋白和黏蛋白域分子3(T cell immunoglobulin and mucin-domaincontaining molecules 3,Tim-3)在免疫调节中起重要作用,参与多种疾病的发生、发展,且与疾病免疫逃逸和疾病临床预后明显相关。该研究旨在探讨负性共刺激分子Tim-3在非小细胞肺癌(non-small cell lung cancer,NSCLC)浸润巨噬细胞中的表达及临床意义。方法：采用免疫组织化学法检测126例NSCLC患者中Tim-3的表达水平,分析肿瘤组织浸润巨噬细胞Tim-3的表达水平与临床病理特征间的关系,并进一步分析Tim-3的表达水平对NSCLC患者预后的影响。结果：Tim-3主要分布于巨噬细胞的细胞质和细胞膜中;Tim-3在肿瘤浸润巨噬细胞中的表达水平与肿瘤大小、淋巴结转移及TNM分期均显著相关(P=0.002、0.045和0.022);Tim-3在肿瘤浸润巨噬细胞中的表达水平可显著影响NSCLC患者的生存及预后,在Ⅲ期NSCLC患者中,Tim-3的表达越高,患者总生存期(overall survival,OS)越短(Ⅲ期：χ²=12.910,P=0.000,中位OS分别为80和32个月)。而且,Tim-3的表达水平与Ⅲ期NSCLC患者的无疾病生存期(disease free survival,DFS)也显著相关(χ²=6.135,P=0.013,中位DFS分别为41和24个月),高表达Tim-3的NSCLC患者DFS短。另外,在Ⅲ期NSCLC患者中,Tim-3在淋巴细胞中的表达水平与OS和PFS呈负相关(χ²=4.737,P=0.030,中位OS分别为80和47个月;χ²=5.882,P=0.015,中位DFS分别为41和24个月)。结论：Tim-3在肿瘤免疫中起负性调节作用从而促进免疫逃逸,对患者的生存及预后有不良影响。     

Examining Nek2 as a better proliferation marker in non-small cell lung cancer prognosis

The purpose of this study is to identify a better potential biomarker for the prognosis of patients with non-small cell lung cancer (NSCLC). The expressions of Nek2, MCM7, and Ki-67 were evaluated in 270 NSCLC tissues using immunohistochemical and immunofluorescence techniques. Associations between protein expression and clinical pathologic characters were assessed, and the impact on overall survival was analyzed. We detected high levels of Nek2, MCM7, and Ki-67 expression in 25.9, 35.2, and 24.4 % of NSCLC tissues, respectively. Overexpressions of Nek2 were detected more frequently in high T-stage and N-stage cases (P?=?0.000, 0.011). The expressions of Nek2, MCM7, and Ki-67 were correlated with each other. Kaplan-Meier curves indicated that patients with overexpression of Nek2, MCM7, and Ki-67 had a poorer overall survival rate compared to those with low expression for all stages (P?=?0.000). In particular, the patients with Nek2 overexpression had the most negative prognosis. Multivariate Cox regression analysis showed that Nek2, MCM7, and Ki-67 are independent prognostic indicators for NSCLC. Our data suggest that among Nek2 kinase, MCM7, and Ki-67, it is Nek2 kinase that is the more effective tumor proliferation marker of poor prognosis for NSCLC patients. Thus, Nek2 may represent a new potential target for NSCLC therapeutic intervention.     

Aurora-A is a novel predictor of poor prognosis in patients with resected lung adenocarcinoma

Background： The Aurora-A （AurA） gene, a key regulator of mitosis, has been proved as an oncogene in a variety of cancers. The Aur-A overexpression has been proved correlated with aggressiveness of cancer cells. However, the frequency of Aur-A protein overexpression, as well as its association with clinicopathologic parameters and prognosis remain unclear in lung adenocarcinoma （ADC）. This study tried to clarify the clinical significance of Aur-A in patients with resected lung ADC. Patients and methods： A total of 142 informative patients with surgically resected lung ADC and 20 normal lung tissues were enrolled. Western blot and immunohistochemistry （IHC） were utilized to assess protein expression of Aur-A. Result： The expression of Aur-A was elevated in most of tumor tissues compared with the adjacent tissues by western blot. The IHC results showed that Aur-A protein was over-expressed in 98 of 142 （69.0%） tumor sections, while Aur-A was low-expressed in all normal lung sections. A positive correlation between Aur-A overexpression rate and ascending pathologic stages was observed （P〈0.05）. Kaplan-Meier analysis demonstrated that patients with Aur-A high expression had significantly inferior survival compared to those with Aur-A low expression. Both overall survival （OS） and disease-free survival （DFS） of positive overexpression patients were shorter than the negative group （P=0.036, P=0.041, respectively）. Multivariate analysis confirmed that Aur-A expression, as an independent and significant factor for both DFS and OS, could predict a poor prognosis in patients with resected lung ADC （P=0.022, P=0.049, respectively）. Conclusions： Aur-A was overexpressed in lung ADC and overexpression of Aur-A might be a novel predictor for poor prognosis and potential therapeutic target in lung ADC.     

成纤维细胞活化蛋白在非小细胞肺癌组织中的表达及其临床意义

目的： 检测人非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中成纤维细胞活化蛋白（fibroblast activation protein,FAP）mRNA的表达,探讨FAP mRNA与NSCLC临床特征及预后之间的关系。 方法： 2004年6月至2006年12月选取天津医科大学附属肿瘤医院组织库中247例NSCLC患者瘤组织标本和对应的48例癌旁组织标本,患者随访至2011年12月1日。采用实时荧光PCR检测NSCLC组织和正常肺组织中FAP mRNA。临床病理参数与FAP mRNA相对表达量的相关性分析采用Mann-Whitney U检验,以Kaplan-Meier法绘制生存曲线,用log-Rank检验比较患者的生存差异,采用Cox回归模型评估独立的预后因素。 结果： FAP mRNA在NSCLC组织中过表达。NSCLC组织中FAP mRNA表达水平与NSCLC患者KPS评分成正相关（P<0.05）,而与肿瘤原发部位、肿块大小、淋巴结转移、临床分期、组织学类型等其他病理特征无明显关系（P>005）。高表达FAP mRNA 的NSCLC患者与低表达者相比,中位总生存时间（overall survival,OS）无明显差异（43 vs 39个月,P>0.05）。进一步以组织学类型分层分析显示,肺腺癌患者FAP mRNA表达量与临床分期成负相关（P=0.031）,与KPS评分成正相关（P=0.041）。高表达FAP mRNA的肺腺癌患者与低表达者相比,中位OS时间显著延长（42 vs 26个月,P<005）,多因素分析进一步证实FAP mRNA表达是影响肺腺癌患者预后的独立因素。 结论： FAP在NSCLC组织中高表达,FAP mRNA高表达与肺腺癌的临床分期呈负相关,并与肺腺癌患者的预后密切相关。     

NACK的表达水平对非小细胞肺癌预后的影响

目的:探讨NACK在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其与临床病理特征的关系.方法:采用RT-PCR及Western blot法对35例非小细胞肺癌患者的肺癌组织及癌旁组织的NACK表达水平进行定量分析,以及NACK的表达与非小细胞肺癌临床病理特征的关系,通过生存曲线分析随访病人的总体生存率(OS)和无病生存率(DFS).结果:非小细胞肺癌患者NACK相对表达水平高于正常对照组(P<0.05),其表达与临床分期、分化程度及淋巴结转移显著相关(P<0.05),而与患者的年龄、性别、肿瘤大小、抽烟、病理类型无关(P>0.05).随访3年NACK高表达的病人总体生存率(OS)和无病生存率(DFS)分别为30.7%和34.6%,而低表达者分别为OS 77.8%和DFS 81.8%,两组间差异有显著统计学意义(P<0.001).结论:我们认为NACK的高表达可以作为预测NSCLC预后不良的高危因素,为以后深入研究NACK-Notch调控机制和探索新的治疗靶点提供重要基础.     

Risk stratification and adjuvant chemotherapy after radical resection based on the clinical risk scores of patients with stage IB-IIA non-small cell lung cancer

IntroductionDespite the heterogeneity among patients with stage IB-IIA non-small cell lung cancer (NSCLC), clinically applicable models to identify patients most suitable for receiving adjuvant chemotherapy (ACT) are limited. We aimed to develop a model for risk stratification and the individualized application of ACT.MethodsBetween January 2008 and March 2018, patients with T2N0M0 NSCLC at Sun Yat-sen University Cancer Center were retrospectively enrolled. Survival curves were estimated by Kaplan-Meier method and compared with log-rank test. Cox regression models were used to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was implemented. Subgroup analysis was performed based on clinical risk score (CRS) value and epidermal growth factor receptor (EGFR) mutation status.ResultsOf 1063 patients with T2N0 NSCLC enrolled, 272 patients received ACT. Before PSM, patients with high CRS (>1) had a significantly worse OS and DFS outcomes. In the PSM, the baseline characteristics of the 270 pairs of patients were well matched. ACT was associated with improved OS outcomes for patients with a high CRS, while ACT was associated with improved OS and DFS outcomes in patients with wild-type EGFR. The interaction analysis showed an apparent interaction effect between ACT and EGFR-activating mutations as well as chemotherapy regimens and histology.ConclusionsThe CRS can predict the prognosis of patients with stage IB-IIA NSCLC. ACT could improve the outcome of patients with a high CRS. Patients with non-squamous cell histology receiving pemetrexed plus platinum might benefit more, but not those with EGFR-activating mutations.     

β-tubulin表达与非小细胞肺癌患者术后诺维本联合铂类辅助化疗预后的关系

  目的  探讨β微管蛋白(β-tubulin)在非小细胞肺癌(NSCLC)中的表达情况, 及其与诺维本/铂类(NP)术后辅助化疗预后的关系。  方法  回顾性分析广州医学院第一附属医院2002年1月至2009年12月收治的84例手术完全切除或部分切除的NSCLC患者, 术后以NP方案辅助化疗。应用免疫组织化学S-P法检测患者手术标本β-tubulin中蛋白的表达, 进一步分析其与无病生存时间(DFS)和总生存时间(OS)的关系。  结果  NSCLC患者中β-tubulin蛋白的低表达率为42.9%(36/84), 高表达率为57.1%(48/84), 男性β-tubulin高表达患者多于低表达患者(68.2%vs.31.8%, P=0.032);Ⅰ~Ⅱ期β-tubulin高表达患者多于低表达患者(70.7%vs.29.3, P=0.014);且行根治性手术β-tubulin高表达患者多于低表达患者(61.6%vs.38.4%, P=0.032), 与NSCLC患者的年龄、病理类型、病理分级、淋巴结转移、吸烟史和放疗均无统计学相关性(P > 0.05)。单因素生存分析显示, 经低表达β-tubulin的NP方案辅助化疗的NSCLC患者, 中位DFS短于高表达者(22.6 vs 69.6个月), 两者之间差异无统计学意义(P=0.052), 但高表达β-tubulin患者的DFS在术后13个月后明显优于低表达者; 进一步分层分析显示, 年龄60岁(P=0.032)、腺癌(P=0.034)、中高分化程度(P=0.028)、不吸烟(P=0.016)的β-tubulin高表达者的DFS均明显优于低表达者。、多因素生存分析显示, β-tubulin的表达(RR=2.213, P=0.025)和临床分期(RR=0.319, P < 0.0001)可作为影响DFS的独立预后因素; 临床分期(RR=0.426, P=0.010)和放疗(RR=2.381, P=0.026)可作为影响OS预后的独立指标。  结论  在术后辅以NP化疗NSCLC患者中, β-tubulin高表达者预后比低表达者好, 术后化疗前对β-tubulin蛋白进行免疫组织化学检测, 有利于制定个体化治疗方案, 可能改善生存。      

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.     

C-erbB-2 Onco-Protein Expression in Breast Cancer: Relationship to Tumour Characterisitcs and Short-Term Survival in Universiti Kebansaan Malaysia Medical Centre

Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosedcases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB-2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancerpatients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB-2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patientswere eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpressioncorrelated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity.Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB-2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PRnegativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed inthose with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status,ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However,c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positiveor negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR.Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymphnode status, ER status and tumour grading were the only three independent prognostic factors for OS and DFSin this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariateanalysis showed that it is not an independent prognostic indicator in breast carcinoma in the local population.     

GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis

G-protein-coupled receptor kinase interacting protein 1 (GIT1) is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/PIX forming a functional protein complex that contributes to Rac1/Cdc42 activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the clinical significance of GIT1 expression in non-small-cell lung cancer (NSCLC) and also verified the importance of GIT1-Rac1/Cdc42 axis in stimulating NSCLC cell mobility. The result indicated higher GIT1 expression patients had significantly poorer prognoses in disease-free survival (DFS) and overall survival (OS) compared with lower GIT1 expression patients. Higher GIT1 expression was an independent prognostic factor by multivariate analysis and associated with migration/invasion of NSCLC cells in transwell assay. In vivo studies indicated that GIT1 promotes metastasis of NSCLC cells. Finally, GIT1 was found to stimulate migration/invasion by altering the activity of Rac1/Cdc42 in NSCLC cells. Together, the GIT1 expression is associated with poor prognosis in patients with NSCLC. GIT1 is critical for the invasiveness of NSCLC cells through stimulating the activity of Rac1/Cdc42.