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Journal ArticleDOI

Prognostic impact of vascular endothelial growth factor-A and E-cadherin expression in completely resected pathologic stage I non-small cell lung cancer.

01 Jul 2010-Japanese Journal of Clinical Oncology (Oxford University Press)-Vol. 40, Iss: 7, pp 670-676

TL;DR: Gender, vascular endothelial growth factor-A and E-cadherin expression were significant predictive factors for overall survival in completely resected pathologic stage I non-small cell lung cancer.

AbstractOBJECTIVE: The purpose of this study was to evaluate the value of vascular endothelial growth factor-A and E-cadherin expression as well as other confirmed prognostic factors in predicting the clinical outcome after definitive surgery of pathologic stage I non-small cell lung cancer. METHODS: One hundred and eighty-five consecutive and non-selected patients who underwent definitive surgery for stage I non-small cell lung cancer in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for vascular endothelial growth factor-A and E-cadherin and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. RESULTS: Of the 185 patients studied, 92 cases (49.7%) were strongly positive for vascular endothelial growth factor-A. Vascular endothelial growth factor-A expression was only related to visceral pleural involvement (P < 0.001). A total of 95 carcinomas (51.4%) were E-cadherin-negative tumors. E-cadherin expression correlated with histology (P < 0.001), tumor size (P = 0.001) and visceral pleural involvement (P < 0.001). In univariate analysis by log-rank test, gender, tumor size, lymphovascular invasion, visceral pleural involvement, vascular endothelial growth factor-A expression and E-cadherin expression were significant prognostic factors (P = 0.003, 0.042, 0.026, 0.035, 0.008 and 0.006, respectively). In multivariate analysis, gender, vascular endothelial growth factor-A and E-cadherin expression maintained its independent prognostic influence on overall survival (P = 0.013, <0.001 and 0.036, respectively). CONCLUSIONS: Expression of vascular endothelial growth factor-A is related to visceral pleural involvement, and E-cadherin expression correlates with histology, tumor size and visceral pleural involvement. Multivariate analysis confirmed gender, vascular endothelial growth factor-A and E-cadherin expression were significant predictive factors for overall survival in completely resected pathologic stage I non-small cell lung cancer.

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Journal ArticleDOI
TL;DR: This study analyzed the soluble factors secreted by lung tumor-associated osteoblast (TAOB), which are responsible for increasing cancer progression, to provide novel evidence that inhibition of B MP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients.
Abstract: Bone is a frequent target of lung cancer metastasis and is associated with significant morbidity and a dismal prognosis. Interaction between cancer cells and the bone microenvironment causes a vicious cycle of tumor progression and bone destruction. This study analyzed the soluble factors secreted by lung tumor-associated osteoblast (TAOB), which are responsible for increasing cancer progression. The addition of bone morphogenetic protein-2 (BMP-2), present in large amounts in TAOB conditioned medium (TAOB-CM) and lung cancer patient sera, mimicked the inductive effect of TAOB-CM on lung cancer migration, invasion, and epithelial-to-mesenchymal transition. In contrast, inhibition of BMP by noggin decreases the inductive properties of TAOB-CM and lung cancer patient sera on cancer progression. Induction of lung cancer migration by BMP-2 is associated with increased ERK and p38 activation and the up-regulation of Runx2 and Snail. Blocking ERK and p38 by a specific inhibitor significantly decreases cancer cell migration by inhibiting Runx2 up-regulation and subsequently attenuating the expression of Snail. Enhancement of Runx2 facilitates Rux2 to recruit p300, which in turn enhances histone acetylation, increases Snail expression, and decreases E-cadherin. Furthermore, inhibiting Runx2 by siRNA also suppresses BMP-2-induced Snail up-regulation and cell migration. Our findings provide novel evidence that inhibition of BMP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients.

66 citations


Journal ArticleDOI
Abstract: Background Lymphovascular invasion (LVI) is considered a high-risk pathologic feature in resected non-small cell carcinoma (NSCLC). The ability to stratify stage I patients into risk groups may permit refinement of adjuvant treatment recommendations. We performed a systematic review and meta-analysis to evaluate whether the presence of LVI is associated with disease outcome in stage I NSCLC patients. Methods A systematic search of the literature was performed (1990 to December 2012 in MEDLINE/EMBASE). Two reviewers independently assessed the quality of the articles and extracted data. Pooled hazard ratios (HRs) and 95% confidence intervals (CI) were estimated with a random effects model. Two end points were independently analyzed: recurrence-free survival (RFS) and overall survival (OS). We analyzed unadjusted and adjusted effect estimates, resulting in four separate meta-analyses. Results We identified 20 published studies that reported the comparative survival of stage I patients with and without LVI. The unadjusted pooled effect of LVI was significantly associated with worse RFS (HR, 3.63; 95% CI, 1.62 to 8.14) and OS (HR, 2.38; 95% CI, 1.72 to 3.30). Adjusting for potential confounders yielded similar results, with RFS (HR, 2.52; 95% CI, 1.73 to 3.65) and OS (HR, 1.81; 95% CI, 1.53 to 2.14) both significantly worse for patients exhibiting LVI. Conclusions The present study indicates that LVI is a strong prognostic indicator for poor outcome for patients with surgically managed stage I lung cancer. Future prospective lung cancer trials with well-defined methods for evaluating LVI are necessary to validate these results.

53 citations


Journal ArticleDOI
30 Jun 2014-PLOS ONE
TL;DR: Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.
Abstract: BACKGROUND Many studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC. METHODS Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. RESULTS A total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage. CONCLUSION Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC.

43 citations


Cites background or methods from "Prognostic impact of vascular endot..."

  • ...In these six studies with 717 patients [16,17,19,23,25,26], the combined HR was 1....

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  • ...E-cadherin expression and clinicopathological parameters in patients with NSCLC The following clinicopathological parameters extracted from studies were collected for analysis: histological type [16,17,19,20,29,31,33,35,38–41], grade of differentiation [14– 20,25,31,35,37–39], tumor size [14,15,17,19,35,38], lymph node metastasis [14–17,19,29,31,35,38,41], pleural invasion [16,26,38], vascular invasion [14,16], and TNM stages [16,17,19,20,29,31, 33,35,38–41]....

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Journal ArticleDOI
TL;DR: Gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC are summarized, and it is hypothesized that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies.
Abstract: Epidemiological studies clearly outline some disparities in cancer onset, progression as well as prognosis and therapeutic response between sexes. In particular, in lung cancer, the leading cause of cancer death, at least in Western countries, a gender disparity appears now to emerge, especially for non-small cell lung cancer (NSCLC). Such a disparity is apparently due to a variety of mechanisms, ranging from genetic and epigenetic differences to gender-specific lifestyle as well as to behavioral causes and, clearly, to sex hormones activity. Here we briefly recapitulate gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC, and hypothesize that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies.

36 citations


Cites background from "Prognostic impact of vascular endot..."

  • ...The possible implication of gender-associated risk factors or autoantibodies in modifying tumor microenvironment, including vascular integrity and function, has been instead recently investigated [42,75–77]....

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Journal ArticleDOI
TL;DR: Exposure to decreased E-cadherin expression was associated with poor survival in patients with NSCLC, especially among Asians, but was not significantly correlated with survival for stage INSCLC patients.
Abstract: E-cadherin has been implicated in invasiveness and metastasis. However, the clinical prognostic value of decreased E-cadherin expression in patients with non-small cell lung cancer (NSCLC) remains unsettled. A meta-analysis of eligible studies was performed to quantitatively review the correlation of decreased E-cadherin expression with survival in patients with NSCLC. Thirteen studies, including 2,274 patients, were subjected to final analysis. The rate of decreased E-cadherin expression was 47.6 % overall and 41.4 % for stage I disease. The combined hazard ratio (HR) was 1.41 (95 % CI 0.18-1.65; P = 0.001), indicating that decreased E-cadherin expression had an unfavorable impact on the survival of patients with NSCLC. Further, in the stratified analysis by ethnicity, the combined HR in Asians was 1.49 (95 % CI 1.27-1.71) and in non-Asians was 1.01 (95 % CI 1.00-1.02). However, when only the stage I studies were considered, the combined HR was 1.19 (95 % CI 0.90-1.47; P = 0.576), suggesting that decreased E-cadherin expression has no impact on survival. Decreased E-cadherin expression was associated with poor survival in patients with NSCLC, especially among Asians, but was not significantly correlated with survival for stage I NSCLC patients.

33 citations


Cites background from "Prognostic impact of vascular endot..."

  • ...Two studies created continuous scores for E-cadherin expression [18, 19] with the remaining studies dichotomizing E-cadherin expression according to the proportion of the tissue staining positive for E-cadherin....

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TL;DR: While the absolute number of cancer deaths decreased for the second consecutive year in the United States, much progress has been made in reducing mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years.
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