Chuangui Chen

Lymph node ratio-based staging system as an alternative to the current TNM staging system to assess outcome in adenocarcinoma of the esophagogastric junction after surgical resection

This study aimed to assess the prognostic value of the hypothetical tumor-N-ratio (rN)-metastasis (TrNM) staging system in adenocarcinoma of the esophagogastric junction (AEG). The clinical data of 387 AEG patients who received surgical resection were retrospectively reviewed. The optimal cut-off point of rN was calculated by the best cut-off approach using log-rank test. Kaplan-Meier plots and Cox regressions model were applied for univariate and multivariate survival analyses. A TrNM staging system based on rN was proposed. The discriminating ability of each staging was evaluated by using an adjusted hazard ratio (HR) and a −2log likelihood. The prediction accuracy of the model was assessed by using the area under the curve (AUC) and the Harrells C-index. The number of examined lymph nodes (LNs) was correlated with metastatic LNs (r = 0.322, P < 0.001) but not with rN (r = 0.098, P > 0.05). The optimal cut-points of rN were calculated as 0, 0~0.3, 0.3~0.6, and 0.6~1.0. Univariate analysis revealed that pN and rN classifications significantly influenced patients’ RFS and OS (P < 0.001). Multivariate analysis adjusted for significant factors revealed that rN was recognized as an independent risk factor. A larger HR, a smaller −2log likelihood and a larger prediction accuracy were obtained for rN and the modified TrNM staging system. Taken together, our study demonstrates that the proposed N-ratio-based TrNM staging system is more reliable than the TNM staging system in evaluating prognosis of AEG patients after curative resection.

High expression of glucose-regulated protein 78 (GRP78) is associated with metastasis and poor prognosis in patients with esophageal squamous cell carcinoma

Background Glucose-regulated protein 78 (GRP78) plays an important role in the invasion and metastasis of many human cancers. However, the role of this protein in the progression of invasion and metastasis in esophageal squamous cell carcinoma (ESCC) remains elusive. Patients and methods Immunohistochemistry and Western blot were performed to analyze GRP78 expression in 92 patients with primary ESCC. The correlation of GRP78 expression with clinicopathological factors was analyzed. In vitro, the expression levels of GRP78 were downregulated by small interfering RNA transfection in TE-1 and CaEs-17 ESCC lines. Cell invasion and migration assays were applied to determine the invasion and migratory abilities of ESCC cells. Results Compared with GRP78 in adjacent normal esophageal tissues, GRP78 was overexpressed in ESCC tissues. High GRP78 expression was significantly correlated with positive lymph node metastasis (P=0.035) and advanced tumor stage (P=0.017). Survival analysis revealed that high GRP78 expression was significantly associated with shorter overall survival (P=0.037). In multivariate analysis, GRP78 overexpression was identified as an independent prognostic factor for overall survival (P=0.011). si-GRP78 can significantly decrease the GRP78 expression level and reverse the invasion and migratory abilities of ESCC cells in TE-1 and CaEs-17 cell lines. Conclusion These findings demonstrated that high expression of GRP78 was associated with disease progression and metastasis in ESCC and might serve as a novel prognostic marker for patients with ESCC.

Development of a novel biomarker model for predicting preoperative lymph node metastatic extent in esophageal squamous cell carcinoma 1

The number and range of lymph node metastasis (LNM) are critical prognostic factors in esophageal squamous cell carcinoma (ESCC). Preoperative serum biomarkers are reported to be associated with LNM. However, whether these markers can precisely predict the extent of LNM is not known. The aim of this study was to evaluate the predictive value of preoperative serum SCC-Ag, Cyfra21-1, CEA, CA19-9 and CA72-4 for LNM number and range by retrospectively investigating 577 ESCC patients undergone esophagectomy from 2007-2010. In this study, the positive rate of SCC-Ag and CA19-9 were associated with pN stage. Significant differences were found in CEA and CA19-9 between pN0-1 stage patients and pN2-3 stage patients. However, in subgroup analysis (patients with pN0-1), significant difference was found only in SCC-Ag between pN0 and pN1 stage patients (P=0.003). Middle thoracic ESCC patients were Chosen to analyze the correlation between the range of LNM and biomarkers. SCC-Ag was correlated with paraesophageal and paracardial lymph nodes, but not correlated with subcarinal and left gastric artery lymph nodes. Interestingly, the results of CEA were opposite to that of SCC-Ag. CA19-9 was associated with subcarinal and paracardial LNM (P=0.000, P=0.038). Based on the results, a model incorporated SCC-Ag, CEA and CA19-9 was constructed. The rate of patients with pN2-3 stage was 15.4% and 54.4% in group 1 and 4 of our model. In summary, SCC-Ag was associated with early lymph node metastatic stage, and CEA and CA19-9 have a close relationship with advanced lymph node metastatic stage. The model combining SCC-Ag, CEA and CA19-9 might help identify the preoperative extent of LNM for a subgroup of ESCC patients that can be benefited from neoadjuvant therapy.

Log odds of positive lymph nodes is a novel prognostic indicator for advanced ESCC after surgical resection

BACKGROUND To investigate the prognostic value of the log odds of positive lymph nodes (LODDS) in patients with advanced esophageal squamous cell carcinoma (ESCC) after surgical resection. METHODS Clinical data of 260 patients with advanced ESCC undergoing surgical resection were retrospectively reviewed. Univariate and multivariate analysis were done using the chi-square test and Cox regression model. Receiver-operating-characteristic (ROC) curve was used to compare the association of pathologic nodal (pN) and LODDS with 3- or 5-year overall survival (OS). The cut-point analyses were performed to determine whether there was a cutoff LODDS related to the greatest OS difference. RESULTS The mean follow-up duration was 30 months (range, 3 to 106 months). The 1-, 3-, 5-year OS rates were 70.0%, 41.9% and 30.3%, respectively. Univariate analyses indicated that the 5-year OS rates were 51.2%, 30.5%, 24.6%, and 14.2% in LODDS1, LODDS2, LODDS3, and LODDS4, respectively, and the median survival times were 68.7, 34.6, 24.0, and 14.6 months, respectively (P=0.000) for all patients, and subgroup analysis showed the effect did not change in 155 patients without lymph node (LN) metastasis (P=0.024). Multivariate analysis showed that LODDS [hazard ratio (HR) =1.309, P=0.003] to be independent and significant prognostic factors for all patients, so as in node-negative patients LODDS (HR =1.610, P=0.038). The AUC of LODDS stage (AUC =0.630) was larger than that of pN stage (AUC =0.621) in prediction of 3-year OS, however LODDS were smaller in prediction of 5-year OS (AUC =0.620, 0.631, respectively), and the differences were not statistically significant (P>0.05 all). Lastly, the step analysis identified the best cut-off point for LODDS as -1.2 that is significantly associated with the prognosis of the node-negative patients (P=0.024), and the ROC analysis also indicated that a cut-off value of -1.2 for LODDS provided the highest sensitivity and specificity interestingly. CONCLUSIONS LODDS may be suitable for evaluation of OS in advanced ESCC patients without LN metastasis.