Ping Zhan

Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Lung Cancer A Systematic Review with Meta-Analysis

Background: Vascular endothelial growth factor (VEGF) has been implicated in tumorigenesis and metastasis, and it presumably mediates the proliferation of endothelial cells and promotes vascular permeability. However, the prognostic value of VEGF overexpression in patients with lung cancer remains controversial. Methods: Survival data from published studies were aggregated following a methodological assessment. A systematic review of eligible studies with meta-analysis was performed to quantitatively review the correlation of VEGF overexpression with survival in patients with lung cancer. Results: We conducted a final analysis of 5386 patients from 51 studies. The studies were categorized by histology, disease stage, patient race, VEGF isoform, and laboratory techniques used. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on survival of patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, VEGFC and vascular endothelial growth factor receptor 3 (VEGFR3)/flt-1 overexpression did not significantly correlate with survival in patients with NSCLC. In stage I–III NSCLC with VEGF, the hazard ratio (95% confidence interval) was 1.46 (1.38–1.54) overall, 1.35 (1.24–1.46) in Asian patients, 1.61 (1.49–1.73) in non-Asian patients, 1.41 (1.17–1.65) in SCLC, 1.27 (1.06–1.47) in adenocarcinoma, 1.57 (1.43–1.70) in stage I NSCLC, 1.46 (1.38–1.55) in NSCLC by immunohistochemistry, 1.52 (1.23–1.81) in NSCLC by reverse transcription-polymerase chain reaction, 1.22 (0.96–1.47) in NSCLC with VEGFC, and 1.58 (0.96–2.20) in NSCLC with VEGFR3/flt-1. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas. Conclusion: VEGF overexpression indicates a poor prognosis for patients with NSCLC and SCLC; VEGFC and VEGFR3/flt-1 overexpression was not significantly correlated with survival for patients with NSCLC.

ERCC2/XPD Lys751Gln and Asp312Asn Gene Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 22 Case–Control Studies

Introduction: Published data on the association between XPD Lys751Gln and Asp312Asn gene polymorphism and lung cancer risk are inconclusive. Methods: To derive a more precise estimation of the relationship, a meta-analysis was performed. Results: A total of 22 studies including 15,507 subjects for XPD Lys751Gln genotype and 13,198 subjects for XPD Asp312Asn genotype were examined. For XPD Lys751Gln genotype, significantly increased lung cancer risk was associated with two variant genotypes (CC versus AA: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.12–1.42, p = 0.473 for heterogeneity; C allele carriers versus AA: OR = 1.18, 95% CI = 1.08–1.36, p = 0.732 for heterogeneity). When stratified by ethnicity, significantly increased risks were found among Caucasians but not in Asians. For XPD Asp312Asn genotype, significantly increased lung cancer risk was associated with two variant genotypes (AA versus GG: OR = 1.24, 95% CI = 1.09–1.42, p = 0.104 for heterogeneity; the A allele carriers versus GG: OR = 1.35, 95% CI = 1.13–1.57, p = 0.219 for heterogeneity). When stratified analysis by ethnicity, significantly increased risks were found among Asians but not in Caucasians. In the subgroup analyses by smoking status, there were no significant associations among the nonsmoker subgroup; however, significantly increased lung cancer risks were found in the smoking group. Conclusion: This meta-analysis suggests that the XPD Lys751Gln and Asp312Asn gene polymorphisms are associated with lung cancer risk, the C allele of XPD Lys751Gln genotype is an increased risk factor for developing lung cancer among Caucasians and in smokers, and the A allele of XPD 312 genotype is also an increased risk factor among Asians and in smokers.

XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis

Many studies have examined the association between the XRCC3 Thr241Met gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Ultimately, 17 studies, comprising 4123 lung cancer cases and 5597 controls were included. Overall, for T allele carriers (TC + TT) versus the wild-type homozygotes (CC), the pooled OR was 0.95 (95% CIu2009=u20090.87-1.04 Pu2009=u20090.228 for heterogeneity), for TT versus CC the pooled OR was 0.99 (95% CIu2009=u20090.86-1.15 Pu2009=u20090.315 for heterogeneity). In the stratified analysis by ethnicity, histological types of lung cancer and smoking status, no any significantly risks were found for (C/T + T/T) vs C/C or T/T vs C/C. No publication bias was found by using the funnel plot and Eggers test.Overall, there is no evidence showing a significant correlation between XRCC3 Thr241Met polymorphism and lung cancer risk stratified analysis by ethnicity, histology and smoking status.

CYP1A1 MspI and exon7 gene polymorphisms and lung cancer risk: An updated meta-analysis and review

BackgroundMany studies have examined the association between the CYP1A1 MspI and exon 7 gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent.MethodsTo assess this relationship more precisely, a meta-analysis and review were performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.ResultsUltimately, 64 studies, comprising 18,397 subjects from 49 case-control studies of the MspI genotype and 18,518 patients from 40 case-control studies of the exon 7 genotype, were included. A significantly elevated lung cancer risk was associated with 2 MspI genotype variants (for type C vs Type A: OR = 1.26, 95% CI = 1.12-1.42; for types B and C combined vs Type A: OR = 1.20, 95% CI = 1.13-1.28) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians, lung SCC, lung AC and Male population, not in mixed population, lung SCLC and Female population. However, inconsistent results were observed for CYP1A1 exon7 in our meta-analysis, two variants of the exon 7 polymorphism were associated with a significantly higher risk for lung cancer (for Val/Val vs Ile/Ile: OR = 1.24, 95% CI = 1.09-1.42; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07-1.24) in overall population. In the stratified analysis, a significant assocation was found in Asians, Caucasians, lung SCC and Female population, not in mixed population, lung AD, lung SCLC and Male population. Additionally, a significant association was found in smoker population and not found in non-smoker populations for CYP1A1 MspI and exon7 gene.ConclusionsThis meta-analysis suggests that the MspI and exon 7 polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility and there is an interaction between two genotypes of CYP1A1 polymorphism and smoking, but these associations vary in different ethnic populations, histological types of lung caner and gender of case and control population.

Chlamydia pneumoniae infection and lung cancer risk: A meta-analysis

Chlamydia pneumoniae (C. pneumoniae) is a common cause of acute respiratory infection and has been hypothesised to cause several chronic diseases, including lung cancer. Numbers studies were conducted to analyse the association between C. pneumoniae infection and risk of lung cancer, but no clear consensus had been found. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, Web of Science and CNKI were searched; Data were extracted and analysed independently by two investigators. Ultimately, 12 studies, involving 2595 lung cancer cases and 2585 controls from four prospective studies and eight retrospective studies were included. Overall, people exposed to C. pneumoniae infection had an odds ratio (OR) of 1.48 (95% confidence interval (CI), 1.32-1.67) for lung cancer risk, relative to those not exposed. C. pneumoniae infection was clearly identified as a risk factor for lung cancer in both prospective studies (OR, 1.16; 95% CI, 1.00-1.36) and retrospective studies (OR, 2.17; 95% CI, 1.79-2.63) and in both IgA ≥ 16 cutoff group (OR, 1.22; 95% CI, 1.06-1.41) and the IgA ≥ 64 cutoff group (OR, 2.35; 95% CI, 1.88-2.93). In conclusion, C. pneumoniae infection is associated with an increased risk for lung cancer, higher titre may be a better predictor of lung cancer risk.

TNF-308 gene polymorphism is associated with COPD risk among Asians: meta-analysis of data for 6,118 subjects.

Chronic obstructive pulmonary disease (COPD) is a complex polygenic disease in which gene–environment interactions play a critical role in disease onset and progression. The gene encoding tumor necrosis factor (TNF) is one of several candidate loci for the pathogenesis of COPD and is highly polymorphic. A number of studies have investigated the association between the TNF-308 polymorphisms and COPD risk in different populations, and resulted in inconsistent results. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science, and CNKI databases were searched for case–control studies published from 1966 to April 2009. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twenty-four eligible studies, comprising 2,380 COPD cases and 3,738 controls, were included in the meta-analysis. The pooled result showed that the TNF-308 polymorphisms were significantly associated with an increased risk of COPD (ORxa0=xa01.335, 95% CI: 1.172–1.522, for allele A carriers versus G/G; ORxa0=xa01.330, 95% CIxa0=xa01.174–1.505, for allele A versus allele G). Subgroup analysis supported the results in the Asian populations, but not in the Caucasian populations. When the analysis was limited to only those studies in which the COPD cases and controls were smokers/ex-smokers, the pooled results supported the conclusion. This meta-analysis suggested that the TNF-308 A allele is a more significant risk factor for developing COPD among Asian populations, but not among Caucasians.

CYP2E1 Rsa I/Pst I polymorphism is associated with lung cancer risk among Asians

The genetic polymorphism of CYP2E1 Rsa I/Pst I is thought to have significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 21 published studies involving 9380 subjects of the association between CYP2E1 Rsa I/Pst I polymorphism and lung cancer risk. For the homozygote c2/c2 and c2 allele carriers (c1/c2+c2/c2), the pooled ORs for all studies were 0.734 (95% CI=0.628-0.847; P=0.035 for heterogeneity) and 0.852 (95% CI=0.777-0.933; P=0.004 for heterogeneity) when compared with the homozygous wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same significant risks were found among Asians for both the c2 allele carriers and homozygote c2/c2. Among mixed populations, only significant risk was associated with c2 allele carriers. No significant associations were found in all Caucasians genetic models. In the subgroup analyses by pathological types, for lung SC the ORs of the c2 allele carriers and the homozygote c2/c2 were 0.749 (95% CI=0.683-0.813; P=0.247 for heterogeneity) and 0.726 (95% CI=0.662-0.847; P=0.006 for heterogeneity), respectively. In the subgroup analyses by smoking status, there were no significant associations among smokers or non-smokers subgroup. This meta-analysis suggests that CYP2E1 Rsa I/Pst I c2 allele is a decreased risk factor for the developing lung cancer among Asians and lung SC.

TNF-308 gene polymorphism and tuberculosis susceptibility: a meta-analysis involving 18 studies

A number of studies have investigated the association between TNF-308 (rs1800629 G/A) polymorphisms and the susceptibility towards tuberculosis (TB) in different populations. However, many of these studies provided inconsistent results. In this study, a systematic review and meta-analysis of the published studies was performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science and CNKI databases were searched for case–control studies published up to Jan 2011, we used no lower date limit. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 18 publications from 2001 to 2010, involving 2584 TB cases and 3817 controls were included. Overall, for the A allele carriers (G/Axa0+xa0A/A) vs. homozygote GG, the pooled OR was 1.03 (95% CIxa0=xa00.89–1.19; Pxa0=xa00.912 for heterogeneity). For the allele A vs. allele G, the pooled OR was 1.07 (95% CIxa0=xa00.93–1.22; Pxa0=xa00.013 for heterogeneity). In the stratified analysis by ethnicity, among Asians significant risk was found for allele A vs. allele G (ORxa0=xa01.22, 95% CIxa0=xa01.02–1.47; Pxa0=xa00.152 for heterogeneity), no significant risks were found among Caucasians. This meta-analysis indicated that the TNF-308 polymorphism was not associated with the risk of TB in the total population, however the significant risk for TNF-308 A allele was found among Asians not Caucasians.

Expression of caveolin-1 is correlated with disease stage and survival in lung adenocarcinomas

Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its significance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients.

The Relationships between cyclin D1 Expression and Prognosis of Non-small Cell Lung Cancer

Background and objective cyclin D1 is a member of the cyclin family, and it has been proven that it plaied an important role in tumorigenesis, invasion and metastasis. We performed a retrospective study on the cyclin D1 expression in non-small cell lung cancer (NSCLC) according to the clinical characteristics. Methods One hundred fifteen postsurgical NSCLC patients were investigated. Immunohistochemistry was used to evaluate the cyclin D1 expression. Results Overall survival was significantly lower in patients with cyclin D1-high expression of tumors than those with cyclin D1 low expression of tumors (χ2=5.132, P=0.023). In early stage patients (stage Ⅰ, Ⅱ), the overall survival was significantly lower in patients with cyclin D1-high expression of tumors than those with cyclin D1-low expression of tumors (χ2=6.863, P=0.009). cyclin D1 status (hazard ratio=0.630;P=0.035), differentiation (hazard ratio=0.399; P < 0.001), and pTNM (hazard ratio=1.576; P < 0.001) to be independent prognostic factors for NSCLC patients. Specifically, the cyclin D1 status (hazard ratio=0.188;P=0.008) was a significant prognostic factor for patients with stage Ⅰ NSCLCs. Conclusion cyclin D1 expression is an independent prognosis factor for postoperative patient in stage Ⅰ, Ⅱ NSCLCs.