Abstract 610: Paired alterations of 35-gene expressing profiles before and after neoadjuvant chemoradiation in esophageal squamous cell carcinoma patients impact clinical prognosis

Abstract

Abstract Purpose: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. The aim of this study was to evaluate alterations of the 35-gene expression profiles in irradiated esophageal tissues before and after chemoradiation. Materials and Methods: A total number of 50 patients with Esophageal squamous cell carcinoma (ESCC) received neoadjuvant CCRT were retrospectively reviewed. The prescribed radiation dose for gross tumor and metastatic lymph nodes or subclinical mucosal/submucosal disease and regional lymphatic basin were 48 Gy and 43.2 Gy, respectively. All patients underwent CCRT using the intensity-modulated radiation therapy in 24 fractions and received concurrent chemotherapy with cisplatin. A 35-gene expression profile derived from reported ESCC-specific next-generation sequencing was performed. Paired 35-gene expression profiles were analyzed using pre-CCRT biopsy and post-CCRT esophagectomy specimens. In vitro validation of differential expression genes by using human ESCC cell lines 81T and TE2 was performed using the same 35-gene panel. Results: The alterations in mutation of genes between pre-CCRT biopsy and post-CCRT surgical specimens (delta expression profiles) correlated with pathological complete remission, overall survival and progression free survival. Among the delta expression profiles, the most significant alterations with prognostic impact were noted in MYH4 (p.Gln1210fs) and TTN (p.Asp7145His). Mutation of MYH4 (p.Gln1210fs) and TTN (p.Asp7145His) were demonstrated with favorable and unfavorable impact on rate of pathological complete remission, respectively. The mutation of MYH4 was also noted in human ESCC cell lines 81T and TE2 cells. Conclusion: By using the 35-gene expression profiles, specific mutations correlated to prognosis in esophageal squamous cell carcinoma patients receiving neoadjuvant chemoradiation and esophagectomy were found. The role of MYH4 mutation in treatment outcome and development as therapeutic target of esophageal squamous cell carcinoma remains to be clarified. Citation Format: Yu-Jen Chen, Prerana Bhan, Terry Wu, Hang Chang, Chi-Jung Lee. Paired alterations of 35-gene expressing profiles before and after neoadjuvant chemoradiation in esophageal squamous cell carcinoma patients impact clinical prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 610.