No abstract

Background: Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC. Methods: We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed. Result: Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues ( P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC. Conclusions: Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 ( CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 ( CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1 . The glutathione S-transferase mu 1 ( GSTM1 ) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

Purpose: The serine peptidase inhibitor, Kunitz type 1 antisense RNA1 ( SPINT1-AS1 ), a long non-coding RNA , has been linked to cancer progression. In this study, we aimed to explore the SPINT1-AS1 expression in matched esophageal squamous cell carcinoma (ESCC) and normal tissues, and analyze the potential correlations of SPINT1-AS1 expression with clinicopathological characteristics, in order to evaluate its prognosis and therapeutic value. Methods: SPINT1-AS1 expression was detected in 99 cases of matched ESCC and normal tissues samples using the quantitative real-time polymerase chain reaction method. Results: The expression level (△Ct) of SPINT1-AS1 and SPINT1 mRNA was significantly downregulated in ESCC tissues compared with matched normal tissues ( P =0.0005; P =0.0002, respectively), and there was an obvious positive correlation between SPINT1-AS1 and SPINT1 mRNA expression. Clinicopathological characteristics indicated that SPINT1-AS1 expression was correlated with age and tumor size, while SPINT1 mRNA expression was correlated with age and gender. The receiver operating characteristic (ROC) curve analysis of the expression level of SPINT1-AS1 and SPINT1 mRNA yielded an area under the ROC curve value of 0.638 and 0.625, respectively. The overall survival is shorter in patients with low SPINT1-AS1 expressed than those with high levels of SPINT1-AS1 ( P =0.044), and SPINT1 mRNA expression level is associated with the OS ( P =0.001). Univariate and multivariate analysis suggested that SPINT1-AS1 was an independent prognostic indicator in ESCC. Conclusions: We found that the expression of SPINT1-AS1 and SPINT1 mRNA is downregulated in ESCC tissues, which could contribute to tumor progression. SPINT1-AS1 and SPINT1 mRNA may be therapeutic targets and prognosis markers for ESCC.