Esophageal cancer (ESCA) is one of the most common malignant
tumors of the digestive system worldwide. As a first-line
drug for
chemotherapy,
cisplatin resistance is the major obstacle in the successful treatment of
esophageal cancer. Previous studies largely failed to identify the key genes associated with
cisplatin resistance. Hence, the aim of this study was to screen the
cisplatin resistance-related genes of
esophageal cancer using CRISPR/Cas9 gene-editing technology and Brunello iBar library. Of note, we identified ERCC8 as a novel
cisplatin-resistant gene by high-throughput sequencing and
cisplatin resistance assays. Based on KEGG and GO analysis, we hypothesized that the mechanism of ERCC8 involvement in
cisplatin resistance is through binding to damaged
DNA to perform nucleotide excision repair, contributing to the restoration of basic
DNA functions and cellular life activities in ESCA. In addition, Cell proliferation and wound healing assay confirmed that ERCC8 had little effect on the proliferation and migration of
esophageal cancer cells in vitro. Survival analysis showed that ERCC8 expression was not associated with OS, DSS, or FPI in patients with ESCA. Immuno-infiltration analysis indicated that increased ERCC8 expression is associated with NK cells, macrophages, T helper cells, Th1 cells, and Th2 cells. Collectively, ERCC8 may serve as a new
biomarker for predicting
cisplatin resistance and have the prospect of becoming an effective target for the clinical treatment of
cisplatin resistance in ESCA.