Non-Targeted Metabolomics Reveals the Metabolic Alterations in Response to Artificial Selective Breeding in the Fast-Growing Strains of Pacific Oyster

Pacific oyster(Crassostrea gigas)is one of the most important mollusks cultured all around the world.Selective breeding programs of Pacific oysters in China is initiated since 2006 and developed the genetically improved strain with fast-growing trait.However,little is known about the metabolic signatures of the fast-growing trait.In the present study,the non-targeted metabolomics was performed to analyze the metabolic signatures of adductor muscle tissue in one-year old Pacific oysters from fast-growing strain and the wild population.A total of 7767 and 10174 valid peaks were extracted and quantified in ESI^(+)and ESI^(−)modes,resulting in 399 and 381 annotated metabolites,respectively.PCA and OPLS-DA revealed that considerable separation among samples from fastgrowing strain and wild population,suggesting the differences in metabolic signatures.Meanwhile,81 significantly different metabolites(SDMs)were identified in the comparisons between fast-growing strain and wild population,based on the strict thresholds.It was found that there were highly correlation and conserved coordination among these SDMs.KEGG enrichment analysis indicated that the SDMs were tightly related to pantothenate and CoA biosynthesis,steroid hormone biosynthesis,riboflavin metabolism,and arginine and proline metabolism.Of them,the CoA biosynthesis and metabolism,affected by pantetheine and pantothenic acid,might be important for the growth of Pacific oysters under artificial selective breeding.The study provides the comprehensive views of metabolic signatures in response to artificially selective breeding,and is helpful to better understand the molecular mechanism of fastgrowing traits in Pacific oysters.

A novel recurrence-associated metabolic prognostic model for risk stratification and therapeutic response prediction in patients with stage Ⅰ lung adenocarcinoma

Objective:The proportion of patients with stageⅠlung adenocarcinoma(LUAD)has dramatically increased with the prevalence of low-dose computed tomography use for screening.Up to 30%of patients with stageⅠLUAD experience recurrence within 5 years after curative surgery.A robust risk stratification tool is urgently needed to identify patients who might benefit from adjuvant treatment.Methods:In this first investigation of the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,we developed a recurrence-associated metabolic signature(RAMS).This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognoses of patients with stageⅠLUAD.The clinical significance and immune landscapes of the signature were comprehensively analyzed.Results:Based on a gene expression profile from the GSE31210 database,functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stageⅠLUAD with relapse from those without relapse.We then identified a metabolic signature(i.e.,RAMS)represented by 2 genes(ACADM and RPS8)significantly related to recurrence-free survival and overall survival times of patients with stageⅠLUAD using transcriptome data analysis of a training set.The training set was well validated in a test set.The discriminatory power of the 2 gene metabolic signature was further validated using protein values in an additional independent cohort.The results indicated a clear association between a high risk score and a very poor patient prognosis.Stratification analysis and multivariate Cox regression analysis showed that the RAMS was an independent prognostic factor.We also found that the risk score was positively correlated with inflammatory response,the antigen-presenting process,and the expression levels of many immunosuppressive checkpoint molecules(e.g.,PD-L1,PD-L2,B7-H3,galectin-9,and FGL-1).These results suggested that high risk patients had immune response suppression.Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high risk patients.However,the patients could respond better to chemotherapy.Conclusions:This study is the first to highlight the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,and is the first to also develop a clinically feasible signature.This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm.