Abstract

The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.

Highlights

  • Esophageal cancer (EC) is one of the common malignant tumors that threaten the health of human beings, with its incidence ranking seventh and cancer-related death ranking sixth worldwide [1]

  • Five candidate anti-tumor-associated antigens (TAAs) autoantibodies corresponding to P53, PTEN, GNA11, GNAS, and SRSF2 were identified by the Mann–Whitney U test and receiver operating characteristic (ROC) analysis [20]

  • In the Esophageal squamous cell carcinoma (ESCC) group and normal control group, the positive rates of five anti-TAA autoantibodies ranged from 16.28% to 34.88% and 8.16% to 16.33%, respectively

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Summary

Introduction

Esophageal cancer (EC) is one of the common malignant tumors that threaten the health of human beings, with its incidence ranking seventh and cancer-related death ranking sixth worldwide [1]. Relevant studies pointed out that early diagnosis of EC can significantly improve its poor prognosis, with a 5-year survival rate reaching as high as 80%–90% [7, 8]. Researchers have suggested that autoantibodies against tumor-associated antigens (TAAs) could be used as diagnostic biomarkers for the early diagnosis of cancer. These anti-TAA autoantibodies are stable in the circulating blood and can be produced as early as several years before the appearance of clinical symptoms [9,10,11,12]. The sensitivity and specificity of these anti-TAA autoantibodies cannot meet the needs of the clinical diagnosis of ESCC as biomarkers.

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