The impact of E-cadherin expression on non-small cell lung cancer survival: a meta-analysis
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.
Citations
More filters
TL;DR: The multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics are summarized.
Abstract: E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics.
244 citations
TL;DR: Genes that regulate functions like unlimited growth potential, survival, genomic instability, angiogenesis, epithelial to mesenchymal transition and apoptosis evasion, are involved in giving lung cancer tumors invasive and metastatic competence.
Abstract: Lung cancer remains one of the most common and malignant cancers worldwide. It is most often diagnosed at late stages, when it has already presented local invasion and distal metastases. The basic stages of invasion and metastasis involve the detachment of tumor cells from the extracellular matrix, invasion of surrounding tissues and basal lamina, intravasation into the blood stream, survival and transport through the blood stream, migration, arrest and extravasation at a distal site and formation of a metastatic lesion. These steps require fundamental mechanisms such as angiogenesis, degradation of matrix barriers, disruption of cell-cell and cell-matrix adhesion and inducement of cellular motility. Genes that regulate functions like unlimited growth potential, survival, genomic instability, angiogenesis, epithelial to mesenchymal transition and apoptosis evasion, are involved in giving lung cancer tumors invasive and metastatic competence. Improving of understanding of the underlying molecular and cellular mechanisms remains an urgent and essential issue, in order to develop new more effective strategies in preventing and treating lung cancer.
124 citations
TL;DR: This study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC, however, downregulated E- cadher in expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients.
Abstract: Background
Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.
75 citations
Cites background from "The impact of E-cadherin expression..."
...Recently, E-cadherin was also reported to be related with gastric cancer or non-small cell lung cancer among Asians but not Europeans [47,48]....
[...]
TL;DR: It is suggested that PD-L1 overexpression had a poor impact on survival of patients with NSCLC, and this meta-analysis indicates a poor prognosis for patients withNSCLC.
Abstract: Background: Observational studies on the prognostic role of programmed cell death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) are controversial.
Methods: To clarify the impact of PD-L1 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios (HR) and their corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival.
Results: A total of five studies with 877 patients were evaluable for this meta-analysis. Our results suggested that PD-L1 overexpression had a poor impact on survival of patients with NSCLC, the HR (95% CI) was 1.43 (1.24-1.63) overall, 1.51 (1.24-1.7954) in Asian patients, 1.35 (1.08-1.63) in non-Asian patients. Moreover, there was no heterogeneity between the studies.
Conclusions: PD-L1 overexpression indicates a poor prognosis for patients with NSCLC.
61 citations
Cites background from "The impact of E-cadherin expression..."
...We found that vascular endothelial growth factor (VEGF) (37), E-cadherin (38) and matrix metalloproteinase 2 (39) might be poor prognostic factor in NSCLC, COX-2 (40) might be poor prognostic factor for stage I NSCLC, the ground glass opacity (GGO) area (41) had a favorable prognostic value of overall survival and relapse-free survival in small lung adenocarcinoma....
[...]
TL;DR: HIF-1 α, which combines other proteins, such as vascular endothelial growth factor (VEGF) or CA IX, might serve as important parameters in evaluating biological behaviour and prognosis of lung cancer; it will be of benefit to clinical treatment and prognostic evaluation.
Abstract: Summary BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) plays an important role in tumour progression and metastasis through activation of many target genes that are especially involved in pivotal aspects of cancer biology. However, the prognostic role of HIF-1α has been controversial in primary patients with lung cancer. This metaanalysis was performed to systematically evaluate whether HIF-1α expression is associated with the clinical outcomes in lung cancer patients. METHODS: We retrieved relevant articles from Cochrane library, PubMed, EMbase, CNKI, CBM, VIP and Wan Fang Databases from inception to May 2012. Studies were selected using specific inclusion and exclusion criteria. A systematic review and meta-analysis was performed on the association between HIF-1α expression and clinical outcomes in lung cancer patients. All analyses were performed using the Revman 5.1 software. RESULTS: A total of 30 studies were identified as eligible for the systematic review and meta-analysis. The expression of HIF-1α was significantly higher than those in normal lung tissue; and III‒IV stage, lymph node metastasis, poorly differentiation, squamous cell carcinoma and small cell lung cancer (SCLC) were significantly higher than those in I‒II stage, no lymph node metastasis, well differentiation, adenocarcinomas and non small cell lung cancer (NSCLC), respectively (odds ratio (OR) = 19.00, 95% confidence interval (CI):12.12–29.78, p <0.00001; OR = 0.23, 95% CI:0.14–0.36, p <0.00001; OR = 3.72, 95% CI:2.38–5.80, p <0.00001; OR = 0.47, 95% CI:0.31–0.70, p <0.00002, OR = 0.24, 95% CI:0.07–0.77, p = 0.02; OR = 0.78, 95% CI:0.63–0.98, p = 0.03). VEGF and CA IX positive expression in HIF-1α positive tumour tissues were significantly higher than those in HIF-1α negative tumour tissues, respectively (OR = 3.23, 95% CI: 1.90–5.46, p <0.0001; OR = 3.84, 95% CI: 2.10–7.03, p <0.0001). The positive HIF-1α tumour tissues of patients had lower 5-year survival rates (OR = 0.13, 95% CI: 0.03–0.47, p = 0.002) and overall survival (relative risk (RR) = 1.68, 95% CI: 1.12–2.50, p = 0.01). CONCLUSIONS: HIF-1α is related to a differing degree of lung cancer cell, lymph node metastasis, post-operative survival time and histology (NSCLC vs. SCLC, adenocarcinomas vs. squamous cell carcinoma). HIF-1 α , which combines other proteins, such as vascular endothelial growth factor (VEGF) or CA IX, might serve as important parameters in evaluating biological behaviour and prognosis of lung cancer; it will be of benefit to clinical treatment and prognostic evaluation.
59 citations
References
More filters
TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
01 Jan 2006
7,442 citations
"The impact of E-cadherin expression..." refers background in this paper
...Despite tremendous efforts to reduce deaths due to lung cancer, the prognosis of lung cancer is still poor, with an approximate 5-year survival rate of 15 % [2]....
[...]
TL;DR: A marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping are notable.
Abstract: The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor-node-metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms.
7,303 citations
"The impact of E-cadherin expression..." refers background in this paper
...Other independent prognostic factors include performance status, age, and weight loss of more than 10 % [4, 5]....
[...]
TL;DR: Overall cancer death rates decreased in all racial/ethnic groups in both men and women from 1998 through 2007, with the exception of American Indian/Alaska Native women, in whom rates were stable.
Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,596,670 new cancer cases and 571,950 deaths from cancer are projected to occur in the United States in 2011. Overall cancer incidence rates were stable in men in the most recent time period after decreasing by 1.9% per year from 2001 to 2005; in women, incidence rates have been declining by 0.6% annually since 1998. Overall cancer death rates decreased in all racial/ethnic groups in both men and women from 1998 through 2007, with the exception of American Indian/Alaska Native women, in whom rates were stable. African American and Hispanic men showed the largest annual decreases in cancer death rates during this time period (2.6% and 2.5%, respectively). Lung cancer death rates showed a significant decline in women after continuously increasing since the 1930s. The reduction in the overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 898,000 deaths from cancer. However, this progress has not benefitted all segments of the population equally; cancer death rates for individuals with the least education are more than twice those of the most educated. The elimination of educational and racial disparities could potentially have avoided about 37% (60,370) of the premature cancer deaths among individuals aged 25 to 64 years in 2007 alone. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population with an emphasis on those groups in the lowest socioeconomic bracket. CA Cancer J Clin 2011. © 2011 American Cancer Society.
4,161 citations
"The impact of E-cadherin expression..." refers background in this paper
...Lung cancer is the leading cause of cancer-related death both in the USA and around the world [1]....
[...]
TL;DR: A number of methods of extracting estimates of the log hazard ratio and its variance in a variety of situations are presented to improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
Abstract: Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
3,998 citations
"The impact of E-cadherin expression..." refers methods in this paper
...In our meta-analysis, when HR and CI were not described in the reports, they were extracted from the data according to the method of Parmar [22]....
[...]
...When not given explicitly in an article, they were calculated from available numerical data in the articles using methods reported by Parmar [22]....
[...]