Multi Omic Analysis to characterize genomic and proteomic alterations in esophageal squamous cell carcinoma

Abstract

Esophageal cancer is the eighth most common cancer in the world. It is the sixth leading cause of cancer mortality in the world according to the recent update, GLOBOCON 2018 [1]. There is considerable geographical variability in incidence of two major histological subtypes of esophageal cancer - Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). ESCC constitutes ~90% of esophageal cancer cases with high incidence in Asian countries extending from Northern China to the Middle East. In India, annually 47,000 new cases and 42,000 deaths are registered for ESCC and Kashmir is identified as one of the high-risk regions. It is estimated to further increase to 92,284 ESCC cases in India by 2040. Poor prognosis of ESCC patients is often due to diagnosis at advanced stages of cancer. The overall survival rate is less than 15% at advanced stages. Surgery remains a mainstay treatment option for ESCC, however, along with surgery, other modalities such as chemotherapy or radiation therapy is also given depending upon tumour stage. Tobacco usage and alcohol consumption are well-known risk factors associated with esophageal squamous cell carcinoma. Cigarette smoke and smokeless tobacco are two major ways of tobacco usage. Approximately 30% of the adult Indian population, including males and females, consume tobacco either in the form of smoked tobacco or smokeless tobacco. Tobacco consumption is associated with the risk of developing various health complications including cancer. In India, 42% of total cancer-related deaths in men were accounted for the cancers associated with tobacco consumption [2]. Significant dose-response relationships have been reported between tobacco usage and alcohol consumption with risk of ESCC [3]. There are several carcinogens identified in cigarette smoke and smokeless tobacco including polycyclic aromatic hydrocarbons and nitrosamines. These tobacco carcinogens are known to cause DNA damage by forming DNA adducts which lead to replication errors resulting...