Abstract
Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer, and is the sixth leading cause of cancer-related mortality among all types of cancers. Previously, we found that the homeobox A13 gene (HOXA13) plays a crucial role in the carcinogenesis of ESCC and both Annexin A2 (ANXA2) and superoxide dismutase 2 (SOD2) were its potential targets. Samples from 258 patients from two independent cohorts were collected. RT-qPCR and immunohistochemistry (IHC) were used to detect the expression levels of HOXA13, ANXA2 and SOD2. Kaplan‑Meier survival curve analysis and Cox proportional hazards regression model were employed to determine their prognostic significance. Results showed that ESCC tissues had higher ANXA2 and SOD2 mRNA and protein levels than the non-cancerous tissues. ANXA2 and SOD2 were found to be positively correlated with HOXA13 expression not only at the mRNA level but also at the protein level. In both the study cohort and the validation cohort, the median overall survival time of patients with high expression of HOXA13, ANXA2 and SOD2 was shorter than the survival time of the patients with low expression. The Cox proportional hazards model revealed that both TNM stage and coexpression of HOXA13/ANXA2/SOD2 are independent predictors of overall survival of ESCC patients. In conclusion, the present study demonstrated that ANXA2 and SOD2 are potential target genes of HOXA13 and their coexpression predicts the poor prognosis of ESCC patients.
Highlights
Esophageal cancer is the sixth leading cause of cancer-related mortality worldwide, and esophageal squamous cell carcinomaKey words: esophageal squamous cell carcinoma, prognosis, homeobox A13 gene (HOXA13), Annexin A2 (ANXA2), superoxide dismutase 2 (SOD2), coexpression (ESCC) is the main histologic type of esophageal cancer [1]
To investigate whether they are associated with Esophageal squamous cell carcinoma (ESCC), the mRNA levels of ANXA2 and SOD2 in ESCC and matched non-cancerous specimens were analyzed by RT-qPCR
Expression levels of ANXA2 and SOD2 were significantly higher in the ESCC tissues than levels in the non-cancerous specimens
Summary
Esophageal cancer is the sixth leading cause of cancer-related mortality worldwide, and esophageal squamous cell carcinoma. Homeobox (HOX) genes encode a group of transcription factors, which can directly drive the transcription of target genes [4]. HOX genes play crucial roles in embryogenesis and tumorigenesis. Takahashi et al comprehensively evaluated the expression of all HOX genes in 48 primary ESCC tissues and 7 normal esophageal tissues by RT-qPCR. Their data suggested that disordered expression of HOX genes was significantly associated with the tumorigenesis and development of ESCC [5]. Homeobox A13 gene (HOXA13) was found to be overexpressed in ESCC tissues when compared to that in normal tissues [3]. The prognosis of HOXA13-positive patients was significantly worse than that of HOXA13-negative patients [6]
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