Assessment of prognostic significance of cytoplasmic survivin expression in advanced oesophageal cancer

Survivin is a member of the family of proteins, which inhibit apoptosis (inhibitor of apoptosis proteins - IAP). Expression of survivin was found in colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and breast cancer. There is some recent data indicating the correlation of poor prognosis and worse response to chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC) expressing survivin. The aim of the present study was to assess survivin expression in cancerous tissue of patients with advanced OSCC and to test the potential correlation between survivin expression and clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs), who were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin expression, examined immunohistochemically, was found in 35 (83.33%) cases. No statistically significant correlation between survivin expression in the tumour and patients' gender, TNM stage, or vascular involvement was noted. The mean survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months) was not statistically different to those with negative survivin staining (16+/-6.28 months) as assessed by Mantel-Cox test (p=0.49). Univariate regression analysis revealed UICC staging as the only predictor of survival in the analysed group (p<0.05). These results indicate that the cytoplasmic survivin expression does not seem to be the prognostic factor in advanced cases of OSCC.     

MMP14在非小细胞肺癌中的表达及其与预后的关系

肺癌5年生存率低,侵润和转移是导致其死亡的主要原因.探讨MMP14(matrix mettallo proteinase 14)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达,及其与浸润转移和预后的关系.通过采用免疫组化检测92例NSCLC组织及25例癌旁正常组织中MMP14蛋白的表达,并分析其与临床病理学特征及预后的关系.免疫组化结果显示,MMP14蛋白在NSCLC组织中表达的阳性率为64.1%(59/92),显著高于癌旁正常组8%(2/25)(P<0.001).MMP14阳性率与NSCLC的分化程度、T分期、淋巴结转移和TNM分期相关(P<0.05),而与性别、年龄、吸烟及组织学类型无关(P>0.05).Kaplan-meier生存曲线显示,MMP14阳性表达组的患者5年生存期显著低于阴性表达组(P=0.004).Cox多因素回归分析显示,MMP14不是NSCLC的独立预后因素(P>0.05).MMP14在肺癌的分化、浸润和转移中扮演着重要的作用,并对生存期有一定的影响.     

血清外泌体lncRNA PCGEM1、miR-129-5p与非小细胞肺癌患者临床病理特征及预后的关系

摘要 目的：研究血清外泌体长链非编码核糖核酸（lncRNA）前列腺癌基因表达标记1（PCGEM1）、微小核糖核酸（miR）-129-5p与非小细胞肺癌（NSCLC）患者临床病理特征及预后的关系。方法：选取2016年2月-2018年1月南京脑科医院收治的125例NSCLC患者作为NSCLC组,同期选取体检的70例健康人群作为健康组。采集两组静脉血,提取血清外泌体;采用实时定量聚合酶链式反应（qRT-PCR）检测血清外泌体lncRNA PCGEM1、miR-129-5p表达情况;采用Pearson相关性分析lncRNA PCGEM1与miR-129-5p的关系。并分析血清外泌体lncRNA PCGEM1、miR-129-5p与NSCLC患者临床病理特征的关系。对NSCLC患者行5年随访,绘制Kaplan-Meier曲线分析预后情况,多因素Cox比例风险回归模型分析预后不良危险因素,受试者工作特征（ROC）曲线分析lncRNA PCGEM1、miR-129-5p对NSCLC预后的预测价值。结果：：NSCLC组lncRNA PCGEM1相对表达量高于健康组,miR-129-5p相对表达量低于健康组（P＜0.05）。血清外泌体lncRNA PCGEM1相对表达量与miR-129-5p表达呈负相关（r= -0.420,P＜0.05）。血清外泌体lncRNA PCGEM1、miR-129-5p表达与患者TNM分期、分化程度、淋巴结转移有关（P＜0.05）。Kplan-Meier生存曲线显示,lncRNA PCGEM1低表达组5年生存率69.05%高于lncRNA PCGEM1高表达组35.53%,miR-129-5p高表达组5年生存率68.09%高于miR-129-5p低表达组33.80%。多因素Cox比例风险回归显示,TNM分期III期、有淋巴结转移、lncRNA PCGEM1高表达、miR-129-5p低表达为NSCLC患者预后不良的独立危险因素（P＜0.05）。ROC曲线显示,lncRNA PCGEM1、miR-129-5p联合检测对NSCLC预后的预测曲线下面积（AUC）为0.865,预测价值高于两者单独预测。结论：NSCLC患者血清外泌体lncRNA PCGEM1表达上调、miR-129-5p表达下调,二者表达与NSCLC患者TNM分期、分化程度、淋巴结转移有关,且与患者预后密切相关,对NSCLC预后不良具有较好预测价值。     

非小细胞肺癌组织PAK4、PAK5蛋白表达与上皮-间质转化、临床病理特征和预后的关系分析

摘要 目的：探讨非小细胞肺癌（NSCLC）组织p21激活激酶（PAK）4、PAK5蛋白表达与上皮-间质转化（EMT）、临床病理特征和预后的关系。方法：选取2018年1月～2019年12月我院收治的100例NSCLC患者,收集手术切除的癌组织和癌旁组织标本,采用免疫组化法检测NSCLC组织和癌旁组织中PAK4、PAK5和EMT相关蛋白[E-钙粘蛋白（E-Cad）、N-钙粘蛋白（N-Cad）和波形蛋白（VIM）]表达。分析PAK4、PAK5蛋白表达与NSCLC患者病理特征的关系和与EMT相关蛋白的相关性。根据NSCLC组织中PAK4、PAK5表达分为阳性/阴性表达组,采用K-M法绘制PAK4、PAK5阳性/阴性表达NSCLC患者的生存曲线,多因素Cox回归分析NSCLC患者死亡的影响因素。结果：与癌旁组织相比,NSCLC组织中PAK4、PAK5、N-Cad、VIM蛋白阳性表达率升高,E-Cad蛋白阳性表达率降低（P＜0.05）。二列相关性分析显示,NSCLC组织PAK4、PAK5与E-Cad蛋白阳性表达率呈负相关,与N-Cad、VIM蛋白阳性表达率呈正相关（P均＜0.001）。不同分化程度、TNM分期、淋巴结转移NSCLC患者PAK4、PAK5蛋白阳性表达率比较,差异有统计学意义（P＜0.05）。100例NSCLC患者3年总生存率为56.00%（56/100）。K-M生存曲线分析显示,PAK4、PAK5阳性表达组总生存率低于阴性表达组（P＜0.05）。多因素Cox回归分析显示,低分化、TNM分期为ⅢA期、淋巴结转移和PAK4、PAK5蛋白阳性表达为NSCLC患者死亡的独立危险因素（P＜0.05）。结论：NSCLC组织PAK4、PAK5蛋白表达升高,与EMT、分化程度、TNM分期、淋巴结转移和预后有关,可能成为NSCLC诊治的新靶点。     

Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis

Purpose

The potential prognostic value of survivin in resected non-small cell lung carcinoma (NSCLC) is variably reported. The objective of this study was to conduct a systematic review of literatures evaluating survivin expression in resected NSCLC as a prognostic indicator.

Methods

Relevant literatures were identified using PubMed, EMBASE and Chinese Biomedicine Databases. We present the results of a meta-analysis of the association between survivin expression and overall survival (OS) in NSCLC patients. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses and publication bias were also conducted.

Results

We performed a final analysis of 2703 patients from 28 evaluable studies. Combined HRs suggested that survivin overexpression had an unfavorable impact on NSCLC patients'' survival with no evidence of any significant publication bias (HR = 2.03, 95%CI: 1.78–2.33, Egger''s test, P = 0.24) and no severe heterogeneity between studies (I² = 26.9%). Its effect also appeared significant when stratified according to the studies categorized by histological type, HR estimate, patient race, cutoff point (5%, 10%), detection methods and literature written language except for disease stage. Survivin was identified as a prognostic marker of advanced-stage NSCLC (HR = 1.93, 95%CI: 1.49-2.51), but not early-stage NSCLC (HR = 1.97, 95%CI: 0.76-5.14), in spite of the combined data being relatively small.

Conclusion

This study shows that survivin expression appears to be a pejorative prognostic factor in terms of overall survival in surgically treated NSCLC. Large prospective studies are now needed to confirm the clinical utility of survivin as an independent prognostic marker.     

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population

A failure to undergo apoptosis is widely thought to be an important event in cancer formation and progression. Although there have been many studies in vitro that provide evidence for this suggestion, the roles of apoptosis-associated proteins in cancer tissues in vivo are not as yet fully understood. Moreover, multiple marker analyses of apoptosis-associated protein expression in non-small cell lung cancer (NSCLC) tissues are scarce. In the present study, we investigate the expression of a group of apoptosis-associated proteins including bcl-2, caspase-3, fas, fas ligand (fasL) and survivin, and its clinical significance in NSCLC tissues using immunohistochemistry (IHC). Bcl-2 staining in cancer tissue cells was found in cytoplasm and the positive rate was 38.2% (29/76). Caspase-3 staining was mainly seen in cytoplasm of cancer tissue cells (53.9% [41/76]) with a few cases of nuclear staining (6.6% [5/76]). Fas staining was seen in cytomembrane (15.8% [12/76]) and cytoplasm (42.1% [32/76]) of cancer tissue cells. Likewise, fasL also showed staining in cytoplasm (55.3% [42/76]) and cytomembrane (44.7% [34/76]) of cancer tissue cells. Survivin staining was seen in cytoplasm but not nuclear of cancer tissue cells and the positive rate was 48.7% (37/76). Higher cytoplasm expression of bcl-2 was associated with large tumor size (≥ 3 cm) in NSCLC (p < 0.05). Decreased cytoplasm expression of fas was associated with poor grade in NSCLC (p < 0.05). A negative correlation was found between bcl-2 and cytoplasm caspase-3 expression in NSCLC (p < 0.001). No separate expression of the apoptosis-associated proteins in NSCLC was linked to overall survival of patients (p > 0.05). Multiple marker analyses revealed caspase-3+/cytomembrane fasL- to be linked to better survival of patients with NSCLC (p < 0.05). These results indicate that apoptosis- -associated proteins may impact a variety of clinicopathological features of NSCLC and may co-operatively influence the prognosis of patients with this malignant tumor.     

非小细胞肺癌组织miR-1179、miR-1182表达水平与Notch信号通路、临床病理特征和预后的关系

摘要 目的：探讨非小细胞肺癌（NSCLC）组织微小核糖核酸（miRNA）-1179、miR-1182表达与缺口(Notch)信号通路、临床病理特征和预后的关系。方法：选取2018年1月～2019年12月武汉市中医医院收治的118例NSCLC患者,收集手术切除的癌组织和癌旁组织标本,采用实时荧光定量聚合酶链式反应检测miR-1179、miR-1182和Notch信号通路相关分子表达。分析miR-1179、miR-1182表达与Notch信号通路相关分子和NSCLC患者临床病理特征的关系。根据NSCLC组织中miR-1179、miR-1182表达均值分为高、低表达组,采用K-M法绘制不同miR-1179、miR-1182表达NSCLC患者生存曲线,多因素Cox回归分析NSCLC患者预后的影响因素。结果：与癌旁组织比较,NSCLC组织中miR-1179、miR-1182表达降低,Notch受体1（Notch1） 信使核糖核酸（mRNA）、Notch2 mRNA、Notch3 mRNA、Notch4 mRNA表达升高（P＜0.05）。Pearson相关性分析显示,NSCLC组织中miR-1179、miR-1182表达与Notch1 mRNA、Notch2 mRNA、Notch3 mRNA、Notch4 mRNA表达均呈负相关（P＜0.05）。不同分化程度、TNM分期、淋巴结转移NSCLC患者miR-1179、miR-1182表达比较有统计学差异（P＜0.05）。118例NSCLC患者随访3年,失访5例,3年总生存率为55.75%。K-M生存曲线分析显示,miR-1179、miR-1182高表达组总生存率高于低表达组（P＜0.05）。多因素Cox回归分析显示,低分化、TNM分期Ⅲ期、淋巴结转移为NSCLC患者预后的独立危险因素,miR-1179、miR-1182升高为其独立保护因素（P＜0.05）。结论：NSCLC组织中miR-1179、miR-1182低表达,与Notch信号通路、分化程度、TNM分期、淋巴结转移和预后有关,miR-1179、miR-1182表达可能通过抑制Notch信号通路发挥抑癌作用。     

The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma

To investigate the prognostic significance of Survivin and Nectin-4 expression in breast carcinomas. Imprint smears were obtained from 140 breast carcinoma specimens and studied immunocytochemically for the expression of Survivin and Nectin-4. The results were correlated with several clinicopathological parameters, including five-year survival. Increased Survivin staining pattern correlated with increased grade (p < 0.0001), increased lymph node invasion (p < 0.0001), increased tumor size and reduced survival (p < 0.0001). Elevated Nectin-4 expression also correlated significantly with increased grade (p < 0.0001), increased tumor size (p < 0.0001) and reduced survival (p < 0.0001). In addition, Survivin and Nectin-4 staining patterns correlated strongly with one another (p < 0.0001). However, on multivariate analysis, neither Survivin nor Nectin-4 expression seemed to have an independent impact on survival in our study cases. The findings of our study suggest that increased expression of Survivin and Nectin-4 may indicate a worse prognosis in breast cancer patients. The exact implications of the expression of these markers in breast cancer prognosis and treatment remain to be clarified.     

Prognostic Value of Survivin in Patients with Gastric Cancer: A Systematic Review with Meta-Analysis

Objective

The prognostic significance of survivin for the survival of patients with gastric cancer remains controversial. Thus, the objective of this study was to conduct a systematic review of the literature evaluating survivin expression in gastric cancer as a prognostic indicator.

Methods

Relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases. A meta-analysis of the association between survivin expression and overall survival in patients with gastric cancer was performed. Studies were pooled and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.

Results

Final analysis of 1365 patients from 16 eligible studies was performed. Combined HR suggested that survivin expression had an unfavorable impact on survival of gastric cancer patients (HR=1.39, 95% CI: 1.16-1.68). The unfavorable impact also appeared significant when stratified according to the studies categorized by patients’ ethnicity, detection methods, type of sample, and HR estimate. The combined HR in the English literature showed an inverse effect on survival (HR=1.40, 95% CI: 1.13-1.75), while HR in the non-English literature did not (HR=1.38, 95% CI: 0.93-2.05). When stratified according to the location of survivin expression, combined HR showed that expression in cytoplasm was significantly associated with poor prognosis of gastric cancer patients (HR=1.46, 95% CI: 1.12-1.90). While expression in nucleus was not significantly associated with poor prognosis (HR=1.29, 95% CI: 0.72-2.31), the heterogeneity was highly significant (chi-squared=11.5, I²=74%, p=0.009).

Conclusions

This study showed that survivin expression was associated with a poor prognosis in patients with gastric cancer. Cytoplasmic expression of survivin may be regarded as a prognostic factor for gastric cancer patients. In contrast, survivin expression in nucleus did not have a significant impact on patients’ overall survival.     

lncRNA DGCR5在非小细胞肺癌组织中的表达及其与临床病理特征的相关性分析

摘要 目的：探究lncRNA DGCR5在非小细胞肺癌(NSCLC)组织中的表达及其与临床病理特征的相关性。方法：选取2020年1月至2021年12月在我院肿瘤科收治的进行手术治疗的NSCLC患者86例,在手术期间从患者获得肿瘤和非肿瘤的肺癌旁组织样本。采用qRT-PCR测定肿瘤组织及癌旁组织中lncRNA DGCR5表达水平。分析lncRNA DGCR5表达水平与NSCLC患者性别、年龄、临床分期、T分期、N分期等临床病理参数的关系,lncRNA DGCR5表达水平与患者预后总生存期（OS）和无进展生存期（PFS）的关系。结果：与癌旁组织相比,lncRNA DGCR5在NSCLC肿瘤组织中的表达水平相对较低,差异具有统计学意义（P<0.01）。lncRNA DGCR5表达与肿瘤分化程度、TNM分期、肿瘤体积、淋巴转移和远处转移之间存在明显相关性,差异具有统计学意义（P<0.05）。采用Kaplan-Meier法进行生存分析,研究发现lncRNA DGCR5高表达组中位OS及中位DFS分别显著高于lncRNA DGCR5低表达组（P<0.05）。低分化程度、II+ IIIa临床分期、N1-N3淋巴转移、远处转移、及lncRNA DGCR5 低表达均与NSCLC患者总生存率和无进展生存率相关。结论：LncRNA DGCR5在NSCLC患者肿瘤组织中的表达量降低,NSCLC患者血LncRNA DGCR5表达水平与分化程度、TNM分期、淋巴转移、远处转移及预后具有相关性。LncRNA DGCR5可作为早期诊断和治疗NSCLC的新型生物标志物。     

非小细胞肺癌组织PRRX1、VASH-1与微血管密度、临床病理参数和预后的关系研究

摘要 目的：探讨非小细胞肺癌（NSCLC）组织配对相关同源框蛋白1（PRRX1）、血管抑制蛋白1（VASH-1）与微血管密度（MVD）、临床病理参数和预后的关系。方法：选择2018年1月至2020年1月辽宁省金秋医院行手术切除的156例NSCLC患者的癌组织及癌旁正常组织标本。应用免疫组织化学染色法检测癌组织及癌旁组织PRRX1、VASH-1的阳性表达率,并进行MVD计数。比较PRRX1阳性表达组/阴性表达组、VASH-1阳性表达组/阴性表达组MVD计数。分析PRRX1、VASH-1与NSCLC患者病理参数的关系。随访3年,应用Kaplan-Meier生存曲线分析PRRX1、VASH-1阳性/阴性表达与NSCLC患者预后的关系。结果：与癌旁组织相比,NSCLC患者癌组织PRRX1阳性表达率降低,VASH-1阳性表达率升高（P<0.05）。与PRRX1阴性NSCLC患者相比,PRRX1阳性NSCLC患者癌组织MVD降低,与VASH-1阴性NSCLC患者相比,VASH-1阳性NSCLC患者癌组织MVD升高（P<0.05）。与TNM I~II期、无淋巴结转移NSCLC患者的癌组织相比,TNM Ⅲ A期、淋巴结转移NSCLC患者的癌组织中PRRX1阳性表达率降低,VASH-1阳性表达率升高（P<0.05）。Kaplan-Meier法分析显示,PRRX1阳性组3年总体生存率（OS）、3年无病生存率（DFS）高于PRRX1阴性组（P<0.05）,VASH-1阴性组3年OS、3年DFS高于VASH-1阳性组（P<0.05）。结论：NSCLC患者的癌组织中PRRX1阳性表达率降低,VASH-1阳性表达率升高,与淋巴结转移、TNM分期及不良预后有关。     

Early CYFRA 21-1 variation predicts tumor response to chemotherapy and survival in locally advanced non-small cell lung cancer patients

We have evaluated CYFRA 21-1 serum level variations as an indicator of tumor response and survival in 44 consecutive patients with locally advanced non-small cell lung cancer (NSCLC) treated with induction chemotherapy (IC). Irrespective of the initial CYFRA 21-1 serum concentration, a more than 65% decrease in the serum level after the first chemotherapy course was significantly predictive of an objective tumor response (p = 0.0022). In addition, a more than 80% decrease in this level significantly predicted a better disease-free survival (p = 0.039). In patients with initial CYFRA 21-1 serum levels > 3.3 ng/mL (n = 29), a more than 80% decrease after the first IC course was the most significant predictor of overall survival (p = 0.025) in a Cox analysis including initial staging, tumor response and surgery. We conclude that early monitoring of CYFRA 21-1 serum levels may be a useful prognostic tool for tumor response and survival in stage III NSCLC patients treated by induction chemotherapy.     

BRCA1: a novel prognostic factor in resected non-small-cell lung cancer

Background

Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1).

Methodology and Principal Findings

We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04).

Conclusions

Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.     

胃癌survivin基因mRNA和蛋白的表达与临床病理关系

目的　研究胃癌组织中survivin基因的mRNA和蛋白表达情况及其与临床病理参数的关系。方法　应用原位杂交方法和免疫组化SP法检测 5 4例胃癌 ,34例胃良性病变 ,2 0例胃正常组织标本中survivin基因mRNA及蛋白的表达。并对其与临床病理因素和二者的关系进行分析。结果　Survivin蛋白表达阳性率在胃癌、良性疾病组织和正常组织分别为 87 0 % (47/ 5 4 )、 2 3 5 % (8/ 34)和 15 % (3/ 2 0 ) ;SurvivinmRNA阳性率为 79 6 % (43/ 5 4 )、 2 3 5 % (8/ 34)和2 0 % (4/ 2 0 )。胃癌组远大于正常胃组织和良性疾病组 ,而正常胃组织与胃良性疾病组之间差异无显著性。SurvivinmRNA与蛋白在胃癌中的表达呈正相关 (rs=0 6 79,P <0 0 5 )。且其阳性率高低与性别、年龄、组织学类型无关 ;而与淋巴结转移、TNM分期、组织学分级有关。结论　SurvivinmRNA与蛋白在胃癌中表达较高 ,且与淋巴结转移、TNM分期、组织学分级有关 ,它可作为评估胃癌生物学行为和判断预后的生物学指标。     

早期非小细胞肺癌患者血清巨噬细胞抑制因子-1、趋化素与临床病理特征及预后的关系

目的:探讨早期非小细胞肺癌(NSCLC)患者血清巨噬细胞抑制因子-1(MIC-1)、趋化素(chemerin)水平与临床病理特征及预后的关系。方法:选择72例NSCLC患者(NSCLC组)、53例肺良性疾病患者(良性组)、50例体检健康人群(对照组),分别检测血清MIC-1、chemerin水平,分析血清MIC-1、chemerin水平与NSCLC患者临床病理参数的关系。Kaplan-Meier法分析不同血清MIC-1、chemerin水平NSCLC患者生存时间的差异,COX比例风险回归分析血清MIC-1、chemerin水平与NSCLC患者预后的关系。结果:NSCLC组患者血清MIC-1、chemerin水平高于良性组和对照组(P0.05)。血清MIC-1水平与NSCLC患者年龄、目前吸烟、肿瘤直径、TNM分期、分化程度、复发或转移、生存状态有关(P0.05),chemerin水平与NSCLC患者目前吸烟、TNM分期、复发或转移、生存状态有关(P0.05)。高MIC-1水平患者生存率低于低MIC-1水平患者(P0.05),高chemerin水平患者生存率低于低chemerin水平患者(P0.05)。COX比例风险回归分析结果显示:血清MIC-1、chemerin、TNM分期与NSCLC不良预后独立相关。结论:血清MIC-1、chemerin水平与NSCLC患者部分临床病理参数和预后相关,可作为早期NSCLC患者预后预测的潜在指标。     

Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance

Survivin, an important inhibitor of apoptosis, has been found to play an important role in the initiation, progression, and chemoradioresistance of human malignancies. Previously, we have reported that upregulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. The aim of this study was to assess prognostic significance of survivin protein expression in RCC and analyze its correlation with radiosensitivity of RCC cells. RT-PCR and Western blot assays were performed to detect survivin mRNA and protein expression in normal human kidney epithelial cell line (HKEC) or RCC cell lines. The expression of survivin mRNA in RCC and corresponding nontumor kidney tissues was also detected by RT-PCR. Immunohistochemistry was performed to determine survivin protein expression in 75 cases of RCC tissue samples. Moreover, the association of survivin protein expression with clinicopathogical factors and prognosis of RCC patients was statistically analyzed. Small interfering RNA was used to knockdown the endogenous survivin expression in RCC cell line (ACHN) and evaluate the effects of survivin knockdown on proliferation, apoptosis, and radiosensitivity of RCC cell line. RCC cells showed sufficient expression of survivin mRNA and protein, but the expression of survivin gene was not detected in normal HKEC. Moreover, the expression level of survivin mRNA in RCC tissues was significantly higher than that in corresponding nontumor kidney tissues. The immunostaining of survivin protein was mainly located in cytoplasm of RCC tumor cells. Tumor pathological stage (P = 0.028), grade (P = 0.004), and lymph node metastasis (P = 0.017) of RCC patients were significantly correlated with survivin protein expression. In addition, patients with high survivin levels had a significantly shorter overall survival than those with low levels (P < 0.001), and the expression of survivin protein was an independent prognostic factor for RCC patients (P = 0.008). The expression of survivin gene could be reduced in RCC cell line and survivin knockdown could inhibit growth and enhance in vivo radiosensitivity of RCC cell line by inducing apoptosis enhancement. Taken together, the status of survivin protein expression may be an independent factor for predicting the prognosis of RCC patients and tumor-specific survivin knockdown combined with radiotherapy will be a potential strategy for RCC therapy.     

Expression of survivin and patients survival in non-small cell lung cancer: a meta-analysis of the published studies

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44–2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.     

红细胞分布宽度、中性粒细胞与淋巴细胞比值与晚期非小细胞肺癌患者临床病理特征及预后的关系研究

目的:探讨红细胞分布宽度(RDW)、中性粒细胞与淋巴细胞比值(NLR)与晚期非小细胞肺癌(NSCLC)患者临床病理特征及预后的关系。方法:选择2017年5月至2019年5月我院收治的106例确诊为晚期NSCLC患者(NSCLC组)和门诊接诊的102例体检正常者(对照组)作为研究对象。检测RDW、NLR,分析RDW、NLR与NSCLC患者临床病理特征以及预后的关系。结果:NSCLC组RDW、NLR高于对照组(P<0.05),年龄≥60岁、淋巴结转移NSCLC患者RDW高于年龄<60岁、无淋巴结转移NSCLC患者(P<0.05),TNM分期为Ⅳ期、淋巴结转移NSCLC患者NLR高于TNM分期为Ⅲ期、无淋巴结转移患者(P<0.05)。Kaplan-Meier生存曲线分析结果显示高RDW组、高NLR组NSCLC患者生存率低于低RDW组、低NLR组(P<0.05)。单因素COX回归分析显示分化程度、TNM分期、淋巴结转移、RDW、NLR与NSCLC预后有关(P<0.05),多因素COX回归分析显示淋巴结转移、RDW、NLR与NSCLC患者预后相关(P<0.05)。结论:晚期NSCLC患者RDW、NLR较高,RDW与年龄、淋巴结转移有关,NLR与TNM分期和淋巴结转移有关,高水平RDW、NLR预示着NSCLC预后不良,可作为预后评估的辅助指标。