Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches

Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically CRC.However,the regulatory FAM pathways in CRC require comprehensive elucidation.Methods:The clinical and gene expression data of 175 fatty acid metabolic genes(FAMGs)linked with colon adenocarcinoma(COAD)and normal cornerstone genes were gathered through The Cancer Genome Atlas(TCGA)-COAD corroborating with the Molecular Signature Database v7.2(MSigDB).Initially,crucial prognostic genes were selected by uni-and multi-variate Cox proportional regression analyses;then,depending upon these identified signature genes and clinical variables,a nomogram was generated.Lastly,to assess tumor immune characteristics,concomitant evaluation of tumor immune evasion/risk scoring were elucidated.Results:A 8-gene signature,including ACBD4,ACOX1,CD36,CPT2,ELOVL3,ELOVL6,ENO3,and SUCLG2,was generated,and depending upon this,CRC patients were categorized within high-risk(H-R)and low-risk(L-R)cohorts.Furthermore,risk and age-based nomograms indicated moderate discrimination and good calibration.The data confirmed that the 8-gene model efficiently predicted CRC patients’prognosis.Moreover,according to the conjoint analysis of tumor immune evasion and the risk scorings,the H-R cohort had an immunosuppressive tumor microenvironment,which caused a substandard prognosis.Conclusion:This investigation established a FAMGs-based prognostic model with substantially high predictive value,providing the possibility for improved individualized treatment for CRC individuals.

Effect of high exposure of chlorogenic acid on lipid accumulation and oxidative stress in oleic acid-treated HepG2 cells

Objective：To evaluate the effect of high concentration of chlorogenic acid（CGA）on non-alcoholic fatty liver disease（NAFLD）in normal and oleic acid（OA）treated Hep G2 cells,as well as the underlying mechanism involved in the fat accumulation,oxidative stress and insulin resistance（IR）induced by CGA treatment.Methods：OA（0.5 mmol/L）induced hepatic steatosis was established in Hep G2 cells as an in vitro model of NAFLD.The normal and OA-treated Hep G2 cells were treated by CGA（0,0.5,1,and 2 mmol/L）for24 h,then cellular lipid droplets,reactive oxygen species（ROS）,and glucose uptake were evaluated by Oil Red O staining and cellular biochemical assays,respectively.Signaling pathways involved in adipogenesis including SREBP-1c and PNPLA3,oxidative stress,and IR including CYP2E1 and CYP4A,were investigated by Western blot and RT-q PCR.Results：CGA（0.5,1,and 2 mmol/L）treatment increased the cellular lipid droplets and the expression of SREBP-1c and PNPLA3 in the tested cells.Additionally,2-NBDG uptake was significantly increased,whereas the cellular ROS and protein levels of CYP2E1 and CYP4A were significantly decreased in OA-treated cells.Conclusion：Our results suggest that high concentrations of CGA ameliorated OA-induced oxidative damage and IR likely by inhibiting the expression of CYP2E1 and CYP4A,and promoted lipid accumulation by inducing the expression of SREBP-1c and PNPLA3 in the tested cells.