Published online May 21, 2024. doi: 10.3748/wjg.v30.i19.2575
Revised: March 9, 2024
Accepted: April 24, 2024
Published online: May 21, 2024
Lactate, previously considered a metabolic byproduct, is pivotal in cancer progre
To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.
RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package “DESeq2” in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further ana
In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes (SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting
We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.
Core Tip: Our article presents the first study on lactylation modification in pancreatic cancer, establishing a lactylation-related signature that offers new strategic directions for tumor prognosis prediction and combination antitumor immunotherapy. It employs an innovative approach, combining both dry lab and wet lab experimental methods, to validate the genes most closely associated with lactylation.