Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma

BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS 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 analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC 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 selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-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 cells.In vivo validation was performed using an established tumor model.RESULTS 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 lactylationrelated 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 the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION 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.

Eruptive Cutaneous Collagenoma: Report of Two Cases

Introduction:Eruptive cutaneous collagenoma is non familial connective tissue nevi of unknown etiology presented with an abrupt onset.To date,the literatures on eruptive cutaneous collagenoma are extremely rare in china.Case present:Two women presented with multiple asymptomatic,skin-colored papules and nodules on the trunk and extremities with no systemic involvement.Histopathology revealed dense,coarse collagen fibers by hematoxylin-esoin stain and decreased,fragmented elastic fibers by Elastic stain compared with the normal skin.Basing on these findings,the diagnosis of eruptive cutaneous collagenoma was made.No specific treatment was given.Discussion:Eruptive cutaneous collagenoma is a very rare dermatosis that is often misdiagnosed as other connective tissue nevi.The pathogenesis is unclear,and also no efficient treatment is available.It is usually diagnosed based on clinical and histopathological findings.Conclusion:The present cases are relatively rare type of eruptive cutaneous collagenoma that provide more experience for clinician,and may be helpful for them to make correct diagnosis for suspicious cases.