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
Summary
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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