Significance of Biomarkers in Squamous Cell Lung Carcinoma
Significance of Biomarkers in Squamous Cell Lung Carcinoma
Objective The aim of this study was to evaluate the prognostic value of E-cadherin, β-catenin, vimentin and S100A4 expression in a cohort of squamous cell lung carcinoma (SqCC) patients.
Methods Tumours from 204 patients with surgically resected SqCC were used for the immunohistochemical analyses of E-cadherin, β-catenin, vimentin and S100A4 expression. Correlations between the expression of these markers and clinicopathological parameters were analysed using the χ test. The prognostic value of these markers was evaluated using univariate Kaplan–Meier survival analyses and multivariate Cox proportional hazards model analyses.
Results Significant associations between E-cadherin expression and T stage (p=0.040), histological differentiation (p=0.005), lymph node metastasis (p<0.001), and recurrence (p<0.001) were identified. Decreased β-catenin expression was significantly correlated with T stage (p=0.003) and lymph node metastasis (p=0.010). Vimentin expression was associated with histological differentiation (p=0.017) and lymph node metastasis (p=0.001). Moreover, significant correlations were observed between S100A4 expression and lymph node metastasis (p=0.020) and recurrence (p<0.001). In the univariate analyses, high E-cadherin expression was a positive indicator for overall survival (OS) (p<0.001) and disease-free survival (DFS) (p<0.001), whereas high S100A4 or vimentin expression were negative indicators for OS (p<0.001 and p=0.010, respectively) and DFS (p<0.001 and p=0.006, respectively). In the multivariate analyses, E-cadherin and S100A4 expression were independent prognostic factors for OS (HR 0.697, 95% CI 0.524 to 0.926, p=0.013, and HR 1.508, 95% CI 1.122 to 2.027, p=0.007, respectively) and DFS (HR 0.634, 95% CI 0.471 to 0.852, p=0.003, and HR 1.490, 95% CI 1.101 to 2.015, p=0.010, respectively).
Conclusions Effective analysis of E-cadherin and S100A4 expression may allow for the identification of patients who are at a high risk of recurrence and poor prognosis in SqCC.
Lung cancer has become the second leading cause of death in China after liver cancer, and its incidence has increased by 465% over the past 30 years. Despite recent improvements in the diagnosis and treatment of lung cancer, its prognosis remains poor, with 5-year survival rates of less than 15%. Recurrence is the most common cause of treatment failure for non-small cell lung cancer (NSCLC) patients after resection. For recurrent lung cancer, customised chemotherapy is more frequently used for the treatment of adenocarcinoma than for the treatment of squamous cell lung carcinoma (SqCC). Molecularly targeted therapies (such as erlotinib and bevacizzumab) have recently been developed for the treatment of adenocarcinoma. By contrast, few therapeutic options exist for the treatment of recurrent SqCC. Thus, there is an urgent need to evaluate the biological characteristics of SqCC to identify the factors that are related to recurrence following surgery.
The epithelial-to-mesenchymal transition (EMT) is a process that can lead to a spectrum of epithelial cellular changes, including loss of polarity and adhesion, increased mobility and the acquisition of a mesenchymal phenotype. This process was originally identified during embryonic development. Thereafter, biological data were collected, and several experimental studies were performed; today, the concept that the EMT is a critical event in the invasion, progression and metastasis of epithelial cancers is well established. Furthermore, acquisition of the features of the EMT has been associated with chemoresistance, which may allow for recurrence and metastasis to occur after treatment with a standard chemotherapeutic treatment. Recent studies have reported that cancer stem cells and microRNA may also be involved in the EMT. EMT pathway inhibitors are under development and consideration for use in cancer treatment. Evaluation of the specific molecules in the EMT pathway, and the identification and selection of patients who would benefit most from EMT pathway inhibitors is an important issue. Several studies have investigated the association between the expression of EMT-related markers and survival in patients with NSCLC. However, subgroup analyses (eg, those investigating the prognostic value of these markers in SqCC) are rare. The two major histological subtypes of NSCLC, SqCC and adenocarcinoma, differ in their clinical biological behaviour. Many studies have demonstrated the disparate expression and clinical significance of EMT-related markers in SqCC and adenocarcinoma.
Consequently, we examined the expression of four representative EMT-related markers (E-cadherin, β-catenin, vimentin and S100A4) in this study to evaluate the prognostic value of these markers in SqCC and correlate the expression of these markers with clinicopathological parameters.
Abstract and Introduction
Abstract
Objective The aim of this study was to evaluate the prognostic value of E-cadherin, β-catenin, vimentin and S100A4 expression in a cohort of squamous cell lung carcinoma (SqCC) patients.
Methods Tumours from 204 patients with surgically resected SqCC were used for the immunohistochemical analyses of E-cadherin, β-catenin, vimentin and S100A4 expression. Correlations between the expression of these markers and clinicopathological parameters were analysed using the χ test. The prognostic value of these markers was evaluated using univariate Kaplan–Meier survival analyses and multivariate Cox proportional hazards model analyses.
Results Significant associations between E-cadherin expression and T stage (p=0.040), histological differentiation (p=0.005), lymph node metastasis (p<0.001), and recurrence (p<0.001) were identified. Decreased β-catenin expression was significantly correlated with T stage (p=0.003) and lymph node metastasis (p=0.010). Vimentin expression was associated with histological differentiation (p=0.017) and lymph node metastasis (p=0.001). Moreover, significant correlations were observed between S100A4 expression and lymph node metastasis (p=0.020) and recurrence (p<0.001). In the univariate analyses, high E-cadherin expression was a positive indicator for overall survival (OS) (p<0.001) and disease-free survival (DFS) (p<0.001), whereas high S100A4 or vimentin expression were negative indicators for OS (p<0.001 and p=0.010, respectively) and DFS (p<0.001 and p=0.006, respectively). In the multivariate analyses, E-cadherin and S100A4 expression were independent prognostic factors for OS (HR 0.697, 95% CI 0.524 to 0.926, p=0.013, and HR 1.508, 95% CI 1.122 to 2.027, p=0.007, respectively) and DFS (HR 0.634, 95% CI 0.471 to 0.852, p=0.003, and HR 1.490, 95% CI 1.101 to 2.015, p=0.010, respectively).
Conclusions Effective analysis of E-cadherin and S100A4 expression may allow for the identification of patients who are at a high risk of recurrence and poor prognosis in SqCC.
Introduction
Lung cancer has become the second leading cause of death in China after liver cancer, and its incidence has increased by 465% over the past 30 years. Despite recent improvements in the diagnosis and treatment of lung cancer, its prognosis remains poor, with 5-year survival rates of less than 15%. Recurrence is the most common cause of treatment failure for non-small cell lung cancer (NSCLC) patients after resection. For recurrent lung cancer, customised chemotherapy is more frequently used for the treatment of adenocarcinoma than for the treatment of squamous cell lung carcinoma (SqCC). Molecularly targeted therapies (such as erlotinib and bevacizzumab) have recently been developed for the treatment of adenocarcinoma. By contrast, few therapeutic options exist for the treatment of recurrent SqCC. Thus, there is an urgent need to evaluate the biological characteristics of SqCC to identify the factors that are related to recurrence following surgery.
The epithelial-to-mesenchymal transition (EMT) is a process that can lead to a spectrum of epithelial cellular changes, including loss of polarity and adhesion, increased mobility and the acquisition of a mesenchymal phenotype. This process was originally identified during embryonic development. Thereafter, biological data were collected, and several experimental studies were performed; today, the concept that the EMT is a critical event in the invasion, progression and metastasis of epithelial cancers is well established. Furthermore, acquisition of the features of the EMT has been associated with chemoresistance, which may allow for recurrence and metastasis to occur after treatment with a standard chemotherapeutic treatment. Recent studies have reported that cancer stem cells and microRNA may also be involved in the EMT. EMT pathway inhibitors are under development and consideration for use in cancer treatment. Evaluation of the specific molecules in the EMT pathway, and the identification and selection of patients who would benefit most from EMT pathway inhibitors is an important issue. Several studies have investigated the association between the expression of EMT-related markers and survival in patients with NSCLC. However, subgroup analyses (eg, those investigating the prognostic value of these markers in SqCC) are rare. The two major histological subtypes of NSCLC, SqCC and adenocarcinoma, differ in their clinical biological behaviour. Many studies have demonstrated the disparate expression and clinical significance of EMT-related markers in SqCC and adenocarcinoma.
Consequently, we examined the expression of four representative EMT-related markers (E-cadherin, β-catenin, vimentin and S100A4) in this study to evaluate the prognostic value of these markers in SqCC and correlate the expression of these markers with clinicopathological parameters.
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