Development of a novel biomarker model for predicting preoperative lymph node metastatic extent in esophageal squamous cell carcinoma1
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Zhao Ma1,*, Xianxian Wu1,*,#, Bo Xu2, Hongjing Jiang1, Peng Tang1, Jie Yue1, Mingquan Ma1, Chuangui Chen1, Hongdian Zhang1 and Zhentao Yu1
1Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin, China
2Department of Molecular Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
*These authors have contributed equally to this work
Zhentao Yu, email: email@example.com
Keywords: esophageal squamous cell cancer; lymph node metastasis; biomarker; risk prediction; squamous cell carcinoma antigen
Abbreviations: Esophageal squamous cell carcinoma (ESCC), Lymph node metastasis (LNM), Japanese Esophageal Society (JES), A receiver operating characteristic (ROC), The area under the ROC curve (AUC)
Received: June 27, 2017 Accepted: October 12, 2017 Published: November 11, 2017
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.
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