Abstract

BackgroundTo investigate the expression and clinical significance of EFNA1 in broad-spectrum tumors, and to evaluate its relationship with prognosis and biological functions of esophageal carcinoma (ESCA).MethodsEFNA1 expression in various cancers was analyzed according to the data in the TCGA database. The clinical data were integrated, to analyze the relationship with ESCA clinical parameters and prognosis, and EFNA1 expression in ESCA tissue samples was detected by immunohistochemistry (IHC). Based on bioinformatics, the functional background of EFNA1 overexpression was analyzed. EFNA1 knockout cell model was established by EFNA1-shRNA transfecting ESCA cells, and the effect of knocking down EFNA1 on the proliferation of ESCA cells was detected by MTT.ResultsAmong 7563 samples from TCGA, the EFNA1 gene highly expressed in 15 samples with common cancers and endangered the prognosis of patients with tumors. Its overexpression in ESCA and its influence on the prognosis were most significant. EFNA1 expression in 80 samples with ESCA and their paired samples was tested by IHC to verify its high expression (paired t test, P < 0.001) in ESCA tissues. It was found that EFNA1 expression was related to clinical factors (TNM staging, P = 0.031; lymph node metastasis, P = 0.043; infiltration, P = 0.016). Meanwhile, EFNA1 was found to be an independent risk factor based on the COX multi-factor analysis. And to further explore the importance of EFNA1 in tumors, EC-9706 and ECA109 cells were screened from 8 ESCA-related cell lines to build EFNA1 knockdown cell models. The results showed that EFNA1 knockdown significantly inhibited the proliferation of tumor cells (P < 0.05). In terms of molecular mechanism, EFNA1 related genes were significantly enriched in the proliferative pathway according to the pathway enrichment analysis. It was found that knocking down EFNA1 did inhibit cell proliferation based on cell experiments.ConclusionsEFNA1 overexpression in ESCA tissue is related to the prognosis of patients. Knocking down EFNA1 can significantly inhibit the proliferation of ESCA cells.

Highlights

  • To investigate the expression and clinical significance of EFNA1 in broad-spectrum tumors, and to evaluate its relationship with prognosis and biological functions of esophageal carcinoma (ESCA)

  • After further integrating the EFNA1 gene expression and clinical data of 6872 patients, it was found that the prognosis of patients with tumors was aggravated by EFNA1 gene overexpression, especially in patients with ESCA after screening (Fig. 1B)

  • The intensity of EFNA1 expression in the samples was detected with IHC test, showing that EFNA1 expression in cancer tissues was significantly higher than that in adjacent tissues (Fig. 2A, B), which was consistent with ESCA in TCGA (182 tumors and 286 normal tissues), and mRNA levels of EFNA1 were significantly higher in cancer tissues than those in normal tissues (P < 0.05) (Fig. 2C)

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Summary

Introduction

To investigate the expression and clinical significance of EFNA1 in broad-spectrum tumors, and to evaluate its relationship with prognosis and biological functions of esophageal carcinoma (ESCA). Esophageal carcinoma (ESCA) is the eighth most common cancer and the sixth most common cause of cancer death in the world [1]. ESCA has high incidence in China, with higher mortality and morbidity than the global average. Surgery is the first choice for ESCA, but the tumor recurrence rate is high after surgery, which is easy to be distant metastasis, with poor long-term effect. It will cause skeletal muscle loss and affect patients’ quality of life [5].

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