Identification of a Novel Fusion Gene (HLA-E and HLA-B) by RNA-seq Analysis in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.

Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity

“…Less than 10 studies of ESCC alterations by RNA-seq have been reported in the literature, most of which of Chinese patients and with similar number of patients to those included in our study [25], [26], [27], [28], [29], [30], [31]. These studies also showed different but comparable estimates of DEG (1425 to 6150) to our findings (6698), depending on sample size, fold-change and P value cutoffs, with a predominance of overexpression.…”

“…Although enrichment of alterations of the Wnt pathway has been reported in ESCC studies with RNA-seq [7], [26], [27], this pathway had not been further explored. Our findings showed 54 DEG in the Wnt pathway, most of which showing overexpression and associated with activation of Wnt signaling.…”

High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China

“…[12,13] More importantly, numerous studies have revealed that HLA-II members are involved in cancers like ESCC. [14–17] However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized.…”