ABHD17C, a metabolic and immune-related gene signature, predicts prognosis and anti-PD1 therapy response in pancreatic cancer

Abstract

Background PDAC is a highly malignant and immune-suppressive tumor, posing great challenges to therapy. Methods In this study, we utilized multi-center RNA sequencing and non-negative matrix factorization clustering (NMF) to identify a group of metabolism-related genes that could effectively predict the immune status and survival (both disease-free survival and overall survival) of pancreatic ductal adenocarcinoma (PDAC) patients. Subsequently, through the integration of single cell sequencing and our center's prospective and retrospective cohort studies, we identified ABHD17C, which possesses metabolic and immune-related characteristics, as a potential biomarker for predicting the prognosis and response to anti-PD1 therapy in PDAC. We then demonstrated how ABHD17C participates in the regulation of the immune microenvironment through in vitro glycolytic function experiments and in vivo animal experiments. Results Through screening for pancreatic cancer metabolic markers and immune status, we identified a critical molecule that inhibits pancreatic cancer survival and prognosis. Further flow cytometry analysis confirmed that ABHD17C is involved in the inhibition of the formation of the immune environment in PDAC. Our research found that ABHD17C participates in the metabolic process of tumor cells in in vitro and in vivo experiments, reshaping the immunosuppressive microenvironment by downregulating the pH value. Furthermore, through LDHA inhibition experiments, we demonstrated that ABHD17C significantly enhances glycolysis and inhibits the formation of the immune suppressive environment. In in vivo experiments, we also validated that ABHD17C overexpression significantly mediates resistance to anti-PD1 therapy and promotes the progression of pancreatic cancer. Conclusion Therefore, ABHD17C may be a novel and effective biomarker for predicting the metabolic status and immune condition of PDAC patients, and provide a potential predictive strategy for anti-PD1 therapy in PDAC.

Novel Heredity Basis of the Four-Horn Phenotype in Sheep Using Genome-Wide Sequence Data

“…Moreover, although the series of SNPs did not reach a significantly associated threshold, they still had high-correlation signals distributed throughout the intergenic region between ARNT2 and ABHD17C and the HOMER2 gene in CHR18. However, studies related to ARNT2 and ABHD17C have focused on the fields of cancer and immunity [41,42]. Other researchers have shown that HOMER2 is expressed in osteoblasts [43,44].…”