Integrative bioinformatics and experimental analyses identify U2SURP as a novel lactylation-related prognostic signature in esophageal carcinoma.

Abstract

The lactylation modification has been implicated in several cancer types; however, the role of lactylation modification-related genes in esophageal carcinoma (EC) remains underexplored. Utilizing a set of 16 lactylation modification-related genes, cohorts of patients with EC were stratified into two distinct clusters, characterized by significant disparities in both survival outcomes and the immune microenvironment. An extensive bioinformatics analysis unveiled 382 differentially expressed genes (DEGs) between these two clusters. A subsequent univariate Cox regression analysis identified 24 DEGs specifically associated with lactylation, forming the basis of a constructed lactylation-related score. The resultant lactylation-related score exhibited notable predictive efficacy for survival and other clinicopathological traits, which was validated through calibration curves, Kaplan-Meier survival curves and the Wilcoxon test. Moreover, the lactylation-related score displayed a close correlation with immune cell infiltration in EC. Notable differential expressions of immune checkpoints and regulators were observed between groups stratified by low and high lactylation scores, with the latter exhibiting a more favorable response to anti-PD-1/PD-L1 therapy. Furthermore, the expression profile of U2 snRNP associated SURP domain containing (U2SURP), a constituent of the lactylation-related score, underwent both ex vivo and in vitro validation. The expression of U2SURP was significantly associated with lactylation levels, histological grade and tumor stage. Notably, knockdown of U2SURP expression inhibited the lactylation levels, immune genes IL-1A and IL-1B, proliferation, migration and invasion of EC cells. In conclusion, the lactylation-related score developed in the present study showed promise in predicting the prognosis and immunotherapeutic responses among patients with EC. Moreover, the identification of U2SUPR as a novel oncogene in EC suggests its potential as a prospective therapeutic target for EC treatment.