Genetic polymorphisms of ATG5 predict survival and recurrence in patients with early-stage esophageal squamous cell carcinoma
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Pei-Wen Yang1,*, Min-Shu Hsieh2,3,*, Ya-Han Chang1, Pei-Ming Huang1 and Jang-Ming Lee1
1Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
2Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
3Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
*These authors have contributed equally to this work
Jang-Ming Lee, email: [email protected]
Keywords: esophageal squamous cell carcinoma (ESCC), ATG5, SNP, recurrence
Received: June 20, 2017 Accepted: July 27, 2017 Published: September 08, 2017
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with high risk of tumor recurrence even among patients with an early pathologic stage of tumor. In the current study, we investigate the association between 20 SNPs of the ATG5 gene and prognosis of patients with early-stage ESCC. A total of 305 patients diagnosed with early-stage ESCC were enrolled in the study and randomly assigned to a training set (n=93) or replication set (n=212). The genotypes of candidate SNPs (single nucleotide polymorphisms) within ATG5 were analyzed and correlated with the prognosis of ESCC patients. We repeatedly demonstrated that 3 SNPs in ATG5, rs1322178, rs3804329, and rs671116, were significantly correlated with the prognosis of patients with early-stage ESCC (HR[95 % CI]=2.01[1.19-3.40], p=0.009 for ATG5: rs1322178; HR[95 % CI]=1.88 [1.08-3.26], p=0.025 for ATG5:rs3804329; HR[95 % CI]=1.73[1.24-2.42], p=0.001 for ATG5:rs671116, in combined group). Both rs1322178 and rs3804329 can predict early distant metastasis of patients. Furthermore, increased expression of ATG5 was observed in ESCC tumor tissue as compared to adjacent normal tissue. Moreover, higher levels of ATG5 expression in both normal and tumor tissues exhibited a trend to correlate with poor prognosis of patients. However, the expression of ATG5 did not correlate with these 3 relevant prognostic SNPs. We concluded that hereditary genetic polymorphisms and gene expression of ATG5 can serve as prognostic predictors of patients with early-stage ESCC.
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