To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer. 1. Introduction Esophageal cancer is one of the most aggressive and life-threatening types of carcinoma in developing countries, and it has a high incidence rate in some geographical regions, particularly in the “Asian esophageal cancer belt,” which extends from the Caspian Littoral in Iran, Turkmenistan, Uzbekistan, and Kazakhstan to the northern provinces of China . Esophageal cancer is among the top 10 causes of cancer-related deaths worldwide . Although some altered oncogenes and tumor suppressor genes have been identified in esophageal cancer (e.g., p53 deletion, p21 alteration, and amplification of CCND1 and c-myc), the fundamental molecular mechanisms leading to esophageal cancer remain unknown [3–6]. The identification of genes that are differentially expressed in esophageal cancer cells allows for the identification of new biomarkers and therapeutic target genes. In addition, this strategy could lead to an improved understanding of the molecular biology and mechanisms of carcinogenesis in esophageal cancer. In contrast to apoptosis, autophagy is primarily a cell survival process; thus, autophagy has been considered an important mechanism in chemoresistance and is known as a survival factor for tumor cells in the early stages of tumorigenesis [7–10]. In this study, suppression subtractive hybridization (SSH) was used to identify
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