Kong Jia Luo

Correlation of p53 Status with the Response to Chemotherapy-Based Treatment in Esophageal Cancer: A Meta-Analysis

BackgroundThe value of p53 status for predicting response to chemotherapy-based treatment in patients with esophageal cancer has been controversial. We conducted a meta-analysis to elucidate the correlation of p53 status with the response to chemotherapy-based treatment.MethodsStudies were searched in PubMed, Embase, and Web of Science (up to September 2012). The p53 status and response to therapy were defined and standardized. Subgroup analyses based on the treatment and histopathology were performed to explore the usefulness of p53 status for predicting response to therapy in esophageal cancer. Sensitivity analyses were conducted by removing specific studies to assess the effects of study quality.ResultsWe included 28 studies with 1497 cases in our meta-analysis. Wild-type form of p53 status (low expression of p53 protein and/or wild-type p53 gene) was associated with high response to chemotherapy-based treatment in esophageal cancer (total major response [MR]: risk ratio [RR]xa0=xa01.09, 95xa0% CIxa0=xa01.03–1.16, Pxa0=xa0.003; pathological MR: RRxa0=xa01.15, 95xa0% CIxa0=xa01.06–1.25, Pxa0=xa0.001; total complete response [CR]: RRxa0=xa01.08, 95xa0% CIxa0=xa01.00–1.17, Pxa0=xa0.040). The similar correlation between the wild-type form p53 and response to therapy were also detected in subgroup analyses (total MR, pathological MR, and total CR in chemoradiotherapy subgroup; total MR in chemotherapy subgroup; total MR and pathological CR in esophageal squamous cell carcinoma [ESCC]). Additionally, patients with wild-type form p53 status had high pathological complete response rate to neoadjuvant chemoradiotherapy in ESCC.ConclusionsThe current meta-analysis suggested that p53 status might be a predictive biomarker for response to chemotherapy-based treatment in esophageal cancer.

MMP1 promotes tumor growth and metastasis in esophageal squamous cell carcinoma

Matrix metalloproteinases play an essential role in the progression of esophageal squamous cell carcinoma (ESCC). Here, we show that MMP1 expression was markedly increased in a majority of ESCC compared with nontumorous tissue. High expressions of MMP1 were closely associated with lymph node metastasis, microvessel density and advanced TNM stage. Kaplan-Meier and multivariate analyses indicated MMP1 as an independent factor for overall survival in two independent cohorts of 613 patients with ESCC. In vitro studies demonstrated that MMP1 overexpression resulted in enhanced cell viability, abilities of colony formation and cell migration. The knockdown of MMP1 in ESCC cells resulted in the opposite phenomenon. Consistently, in vivo data showed that ectopic expression of MMP1 promoted tumor growth and metastasis. Further study revealed that MMP1 facilitated ESCC through the activation of the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway by LY294002 significantly attenuated MMP1-mediated cell proliferation and migration. Taken together, our data suggest that MMP1 functions as an oncogene and serves as a prognostic biomarker and a potential therapeutic target in ESCC.

High expression of Transient potential receptor C6 correlated with poor prognosis in patients with esophageal squamous cell carcinoma

TRPC6 plays a crucial role in the tumor progression of various cancers. The relation between the expression of TRPC6 and clinical prognosis has not been studied yet. Our study was to elucidate the role of TRPC6 in predicting outcomes of patients with esophageal squamous cell carcinoma (ESCC). Fresh frozen samples were collected immediately from 172 patients with ESCC after surgical resection from 2003 to 2008 at Sun Yat-sen University Cancer Center, including 45 pairs of tumor tissues and nontumor tissues. TRPC6 expression was measured by quantitative real-time PCR and Western blotting analyses. TRPC6 mRNA and protein were up-regulated in ESCC tissues when compared with the paired nontumor tissues. High expression of TRPC6 mRNA was associated with the higher pT status (Pxa0=xa00.016) and pathological staging (Pxa0=xa00.040). The 5-year disease-specific survival in the high expression of TRPC6 mRNA group (>188.98, nxa0=xa081) is poorer than that in low-level expression group (≤188.98, nxa0=xa091) (42.1 vs. 62.7xa0%, Pxa0=xa00.004). Stratified analysis according to the pathological stage revealed its discernibility on DSS was only pronounced in patients with pStage III (Pxa0=xa00.015). Cox multivariate analysis revealed that pN category (Pxa0<xa00.001; Relative risk, 2.897, 95xa0% CI 1.830–4.585) and the expression of TRPC6 mRNA (Pxa0=xa00.006; Relative risk, 1.863, 95xa0% CI 1.196–2.902) were independent prognostic factors. TRPC6 mRNA overexpression correlated with poor prognosis in patients with ESCC and might serve as a novel prognostic biomarker for resected ESCC patients in advanced stage.

Metastatic Lymph Node CHIP Expression is a Potential Prognostic Marker for Resected Esophageal Squamous Cell Carcinoma Patients

BackgroundC-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been elucidated. We investigated the correlation of CHIP expression and clinical outcome in a group of T3N1-3M0 surgically resected ESCCs.MethodsTissue microarrays constructed of 234 surgically resected T3N1-3M0 ESCC primary tumors (PTs) and 163 paired metastatic lymph nodes (MLNs), and sections of 56 cancer-adjacent normal epithelial blocks were used for CHIP evaluation by immunohistochemistry. The clinical and prognostic significance of CHIP expression was analyzed statistically.ResultsThe expression level of CHIP in ESCC MLNs was significantly higher than that in PTs (Pxa0<xa00.001). Patients with low MLNs’ CHIP expression demonstrated better overall survival than those with high CHIP expression (median, 44 vs. 17.9xa0months; Pxa0=xa00.010). Multivariate analysis showed that the MLNs’ CHIP expression level was an independent prognostic factor in ESCC (relative risk, 2.157; Pxa0=xa00.028).ConclusionsHigh expression of CHIP in MLNs suggests poor prognosis for patients with resected T3N1-3M0 ESCC. The result suggests that considering the protein expression of metastatic tumors is important for prognostic prediction.

CyclinD1, p53, E-cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: a tissue array analysis.

The correlation of biomarker expression between primary tumors and corresponding metastases has not yet been well reported in esophageal squamous cell carcinoma (ESCC). This study was to confirm whether primary ESCC tumors differ from their regional metastatic lymph nodes (RMLN) in CyclinD1, p53, E‐cadherin, and vascular endothelial growth factor (VEGF) expression and determine prognostic value of their alteration.

Preoperative serum fibrinogen is an independent prognostic factor in operable esophageal cancer.

In order to fully elucidate the association between serum fibrinogen and prognosis of esophageal cancer, we examined serum fibrinogen concentrations in 1512 patients who underwent esophagectomy by the Clauss method. The impact of fibrinogen on overall survival and disease-free survival was analyzed using the Kaplan-Meier method and Cox proportional hazard models. Hyperfibrinogenemia was significantly associated with older age, male gender, smoking, alcohol consumption, weight loss, advanced pathological T stage and lymph node metastasis. Patients with hyperfibrinogenemia exhibited poor OS (HR=1.20, 95%CI: 1.04-1.38, P=0.012) and DFS (HR=1.18, 95%CI: 1.03-1.35, P=0.019). Subgroup analysis further exhibited an significant association between hyperfibrinogenemia and poor OS (P<0.001), DFS (P<0.001) in esophageal squamous cell carcinoma (P<0.001) and early pathological stage (I-II) (P=0.001). Collectively, this study indicates that preoperative serum fibrinogen is an independent prognostic factor for survival in esophageal cancer.

Prognostic value of HOXB7 mRNA expression in human oesophageal squamous cell cancer

Abstract Objective: This study was to determine the role of HOXB7 in predicting outcomes of patients with oesophageal squamous cell cancer (OSCC). Methods: Samples were collected from 179 OSCC patients. HOXB7 mRNA expression was measured by quantitative real-time polymerase chain reaction. Results: HOXB7 mRNA expression was up-regulated in 85.1% of OSCC tumorous tissues, and correlated with age, pathological T and N category, as well as cancer-specific survival (CSS). However, subgroup analysis revealed its discernibility on CSS was only pronounced in early stage. Conclusions: HOXB7 mRNA expression might serve as a novel prognostic biomarker for resected OSCC patients in early stage.

Prognostic Relevance of Id-1 Expression in Patients With Resectable Esophageal Squamous Cell Carcinoma

BACKGROUNDnInhibitor of differentiation or DNA binding 1 (Id-1) is a transcriptional regulator that is associated with enhanced malignant potential and unfavorable survival in many cancers. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) has not been elucidated adequately. The purpose of this study was to explore the pattern of Id-1 expression and analyze its correlation with clinical outcomes of patients with resectable ESCC.nnnMETHODSnPrimary tumors from 407 surgically resected ESCC specimens assembled on tissue microarrays were evaluated with immunohistochemical analysis for Id-1. The effect of Id-1 expression on survival outcome was analyzed by the Kaplan-Meier method.nnnRESULTSnThe expression of Id-1 correlated closely with pT category (p<0.001), pathologic staging (p<0.001), and pN category (p<0.001). The sensitivity, specificity, and accuracy of predicting lymph node metastasis by Id-1 expression were 93.3%, 94.7%, and 94.1%, respectively. Disease-specific survival was significantly favorable in patients with low-level Id-1 expression (p<0.001). Overexpression of Id-1 was also effective to predict unfavorable survival in subgroups of patients with poor differentiation (p<0.001) or with advanced T staging (p<0.001). Multivariate analysis showed that the level of Id-1 expression was an independent prognostic factor in ESCC (p<0.001; relative risk, 1.578).nnnCONCLUSIONSnExpression of Id-1 can be used as a complement for predicting lymph node metastasis in pretreatment workup. High level of Id-1 expression suggested unfavorable prognosis for patients with resectable ESCC.

Maximum standardized uptake value on PET/CT in preoperative assessment of lymph node metastasis from thoracic esophageal squamous cell carcinoma

The presence of lymph node metastasis is an important prognostic factor for patients with esophageal cancer. Accurate assessment of lymph nodes in thoracic esophageal carcinoma is essential for selecting appropriate treatment and forecasting disease progression. Positron emission tomography combined with computed tomography (PET/CT) is becoming an important tool in the workup of esophageal carcinoma. Here, we evaluated the effectiveness of the maximum standardized uptake value (SUVmax) in assessing lymph node metastasis in esophageal squamous cell carcinoma (ESCC) prior to surgery. Fifty-nine surgical patients with pathologically confirmed thoracic ESCC were retrospectively studied. These patients underwent radical esophagectomy with pathologic evaluation of lymph nodes. They all had 18F-FDG PET/CT scans in their preoperative staging procedures. None had a prior history of cancer. The pathologic status and PET/CT SUVmax of lymph nodes were collected to calculate the receiver operating characteristic (ROC) curve and to determine the best cutoff value of the PET/CT SUVmax to distinguish benign from malignant lymph nodes. Lymph node data from 27 others were used for the validation. A total of 323 lymph nodes including 39 metastatic lymph nodes were evaluated in the training cohort, and 117 lymph nodes including 32 metastatic lymph nodes were evaluated in the validation cohort. The cutoff point of the SUVmax for lymph nodes was 4.1, as calculated by ROC curve (sensitivity, 80%; specificity, 92%; accuracy, 90%). When this cutoff value was applied to the validation cohort, a sensitivity, a specificity, and an accuracy of 81%, 88%, and 86%, respectively, were obtained. These results suggest that the SUVmax of lymph nodes predicts malignancy. Indeed, when an SUVmax of 4.1 was used instead of 2.5, FDG-PET/CT was more accurate in assessing nodal metastasis.

TRPV6 plays a new role in predicting survival of patients with esophageal squamous cell carcinoma

BackgroundTRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC.MethodsIn the retrospective study, mRNA level of TRPV6 was examined in patients (Nu2009=u2009174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (Nu2009=u2009218) from Linzhou Cancer Hospital (protein cohort). Statistical analysis was performed to test the clinical and prognostic significance of TRPV6.ResultsTRPV6 was down-regulated in ESCC tissues and cell lines. Patients with downregulation of TRPV6 trended to have a higher rate of advanced pT stage in both mRNA cohort (Pu2009=u20090.089) and protein cohort (Pu2009=u20090.073), though not statistically significant. No significant association was observed between TRPV6 expression and disease-specific survival (DSS) in both two cohorts. However, stratified survival analysis based on the gender showed that in mRNA cohort, downregulation of TRPV6 was associated with an unfavorable 3-year DSS in patients with male (47.3xa0% vs 63.6xa0%, Pu2009=u20090.027) and with favorable 3-year DSS in patients with female (66.7xa0% vs 43.0xa0%, Pu2009=u20090.031). The result was confirmed in protein cohort. Male patients with downregulation of TRPV6 had a poor 3-year DSS (20.0xa0% vs 57.1xa0%,Pu2009<u20090.001) while female counterparts showed an enhanced 3-year DSS (56.1xa0% vs 28.6xa0%, Pu2009=u20090.005).ConclusionTRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients.