UC Irvine

Background

To evaluate the potential of candidate proteins as diagnostic markers or drug targets in esophageal carcinoma (ESCA).

Methods

GSE20347, GSE17351, and GSE45670 were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) between ESCA and normal esophageal tissues from patients were obtained. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. The genes commonly featured in ESCA were screened by least absolute shrinkage and selection operator (LASSO) logistic regression and Boruta feature selection algorithm. The transcriptome data and corresponding clinical data of ESCA were downloaded from The Cancer Genome Atlas (TCGA) public database. Kaplan-Meier survival analysis was used to explore the core genes related to the prognosis of patients. A protein-protein interaction (PPI) network was generated by GeneMANIA to visualize the functional network between genes. Expressions of CRIP2, FOS, and HOXA10 genes in ESCA cells were verified by immunohistochemistry (IHC).

Results

Out of 11,207 genes, 430 DEGs were identified, including 210 up-regulated genes and 220 down-regulated genes. After taking the intersection of LASSO regression and Boruta algorithm, 15 core genes were identified. Survival analyses demonstrated that low expression of CRIP2 (P=2.643e-02), as well as high expression of FOS (P=4.837e-02) and HOXA10 (P=4.97e-02), was significantly associated with the worse prognosis of ESCA patients. The 3 genes were strongly correlated with the content of immune cells and the stage of tumors. The expression of CRIP2 was correlated with the sensitivity of patients to dasatinib; FOS expression was correlated with the sensitivity of patients to erlotinib, and HOXA10 expression affected the sensitivity of patients to cisplatin, dasatinib, erlotinib, and gefitinib. The cBioportal database showed that 56 patients (31%) had the above core gene mutations: CRIP2 (8%), FOS (10%), and HOXA10 (17%). The IHC showed that there were differences in the expressions of these core genes between ESCA patients and the normal population (P<0.05), with ESCA patients showing higher expression.

Conclusions

The low CRIP2 expression and high expressions of FOS and HOXA10 are associated with more advanced tumor stage, which may have the potential to be novel biomarkers for treatment selection in ESCA.