689 MMS22L EXPRESSION AS A PREDICTIVE BIOMARKER FOR THE EFFICACY OF NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract

Abstract Long-term survival in esophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiation therapy (NCRT) followed by surgery. However, effective biomarkers for prediction of pathologic response is still lacking. Therefore, a systematic analysis focusing on genes associated with efficacy of chemoradiotherapy in ESCC will provide valuable insights to understand the molecular features. Methods We collected genes associated with efficacy of chemoradiotherapy by screening publications deposited in PubMed. A specific subnetwork was constructed using Steiner minimum tree algorithm. Then the correlations between gene expression and prognosis of ESCC patients was analyzed using Kaplan–Meier Plotter online resources. The key gene expression was evaluated by quantitative real-time polymerase chain reaction, western blotting analysis and immunohistochemical staining. The predictive performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis. Results We identified 101 genes associated with efficacy of chemoradiotherapy. Moreover, specific molecular network included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1 and UGDH. MMS22L mRNA expression level had most significant association with the ESCC patient outcome (P < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (P < 0.01) and protein levels in tumor compared with normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (P < 0.001). MMS22L levels were inversely correlated with NCRT response in ESCC (P < 0.01). MMS22L yielded an area under the ROC curve (AUC) of 0.847 (P < 0.01). Conclusion Low MMS22L expression could be an effective predictive biomarker for resistance to NCRT in ESCC.