Molecular Analysis of Chinese Esophageal Squamous Cell Carcinoma Identifies Novel Subtypes Associated with Distinct Clinical Outcomes

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a highly heterogeneous cancer with distinct incidence and prognosis. Molecular events driving ESCC subtypes and prognosis have not been established, and little is known regarding Chinese ESCC patients in Xinjiang, China. Methods: Here, we first integrated genomic and transcriptomic data of 125 Chinese ESCC patients from Xinjiang tumor hospital (Urumqi, China). Two independent datasets of GSE53624 and TCGA ESCC were used to confirm results. DNA mutation and overall survival (OS) were analyzed independently in Chinese ESCC cohorts. Findings: Genomic analyses revealed a consistent mutation signatures and discordance of mutated genes across the different ESCC cohorts. In addition, transcriptomic profiling identified three Chinese ESCC subtypes associated with clinical and molecular attributes, including patient survival, lymph node status and genetic profile. Moreover, Chinese ESCC subtypes have distinct metabolic, inflammatory, metastatic, and cell proliferation features and distinct potential therapeutics. Furthermore, the expression of cell cycle- and/or cell proliferation-related genes was higher in cyclin D1 (CCND1)-amplified tumors than in CCND1-normal tumors from Chinese ESCC patients, suggesting that CCND1 amplification promoted cell proliferation. Interpretation: Our findings provide a framework to facilitate the rational categorization of ESCC in Chinese patients and a foundation for new therapies. Funding Statement: This study was supported by the Research Fund of Key Laboratory of Xinjiang oncology (Grant no.2017D04006). Outstanding Youth Science and technology training project fund of Xinjiang, China (Grant no. 2017Q058). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Samples from patients who were not previously treated with chemotherapy or radiation therapy were obtained from the Bank of Tumor Resource, Institute of Oncology, Xinjiang Uygur Autonomous Region in China with informed consent and local Institutional Review Board approval.