Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma
作者机构：Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong UniversityShanghai 200092China
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2024年第30卷第19期
页 面：2575-2602页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Supported by National Natural Science Foundation of China,No.82172737 Shanghai Science and Technology Development Funds(Shanghai Sailing Program),No.22YF1427600
主 题：Pancreatic adenocarcinoma Lactylation Prognosis Immunotherapy Tumor microenvironment
摘 要：BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor *** investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine *** adenocarcinomas are characterized by increased glycolysis and lactate ***,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains *** To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic *** 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 *** on lactylation-related genes were obtained from publicly available *** expressed genes(DEGs)were acquired by using R package“DESeq2in *** COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic *** analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic *** and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were ***,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further ***16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC *** vivo validation was performed using an established tumor *** In this stud
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