An A/C germline single-nucleotide polymorphism in the TNFAIP3 gene is associated with advanced disease stage and survival in only surgically treated esophageal cancer

Abstract

Prognostication of disease relapse and survival is essential for cancer patients and genetic variations in cancer patients may serve as important indicators. A single-nucleotide polymorphism (SNP) mapping to the tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) gene at position 138241110 displays three genotypes (AA, AC and CC). The aim of this study was to evaluate the potential prognostic value of the TNFAIP3-SNP in esophageal cancer (EC). Genomic DNA was extracted from peripheral blood leukocytes of 173 patients who underwent complete surgical resection for EC and did not receive any neoadjuvant or adjuvant therapy. For SNP detection, a 260- bp fragment was PCR amplified, purified and sequenced with tested primers. The product was analyzed by automatic DNA sequencer.The TNFAIP3 genotypes were correlated with clinico-pathological parameters, tumor cell dissemination in bone marrow and clinical outcome. The C-allele carrier presented with higher disease stage (P<0.001). This was predominantly because of the presence of lymph node metastasis (P<0.001). The recurrence rate was higher in C-allele carriers (AC and CC genotype; P=0.004). Kaplan-Meier plots for disease-free (P=0.017) and overall survival (P<0.001) displayed a gene dosage-associated outcome with AA genotype patients presenting the longest and CC genotype patients the poorest survival. In disease stage-adjusted multivariate analysis the TNFAIP3-SNP was identified as an independent prognostic factor for survival (hazard ratio 1.9; P=0.008). The TNFAIP3-SNP allows risk stratification of EC patients and may be a useful tool to identify patients eligible for multimodal therapy concepts.

TNFAIP3 overexpression is an independent factor for poor survival in esophageal squamous cell carcinoma

“…A previous study reported that germline TNFAIP3-SNPs in esophageal cancer had a relationship with AJCC disease stages, lymph node metastasis, and recurrence (23); however, in the present study, the overexpression of TNFAIP3 protein was correlated with differentiation. TNFAIP3 expression was high in well-differentiated ESCC and low in poorly and moderately differentiated cancer in the present study.…”

“…TNFAIP3-SNP was also found to be an independent prognostic factor, but AC and CC genotypes had a relationship with disease-free and overall survival in esophageal cancer (23). Even though it is not on the same condition that deserves to be compared, the present study revealed that TNFAIP3 was found to be an independent prognostic factor, and ESCC patients with high expression of TNFAIP3 had significantly poorer disease-specific survival than those patients with low expression ones.…”

“…Overexpression of TNFAIP3 was also found in breast tumor (19), pancreatic cancer (20), hepatocellular carcinoma (21) and bladder cancer (22). Also, single nucleotide polymorphisms in TNFAIP3 (TNFAIP3-SNPs) were reported to be associated with advanced disease stage and survival in surgically-treated esophageal adenocarcinoma and squamous cell carcinoma (23). However, the clinical study and function of TNFAIP3 in malignant disease is very limited, especially in ESCC.…”

Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer

“…The disease-free survival was defined as the time period from the date of surgery to the date of recurrence, last follow-up or date of death, whichever occurred first. Patients alive without recurrence at the follow-up date were censored 15 . A p-value < 0.05 was considered as statistically significant.…”

Serum Midkine: Emerging Biomarker for Detection and Prognosis of Non-small Lung Cancer

“…The disease-free survival was de ned as the time period from the date of surgery to the date of recurrence, last follow-up or date of death, whichever occurred rst. Patients alive without recurrence at the follow-up date were censored 15 .…”