Identification of a prognostic DNA repair gene signature in esophageal cancer

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC.

Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram.

Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature.

Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.