Genetic susceptibility loci of lung cancer are associated with malignant risk of pulmonary nodules and improve malignancy diagnosis based on CEA levels

Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.

Ganoderma atrum polysaccharide relieves mitochondrial dysfunction to alleviate hydrogen peroxide-induced senescence via activating autophagy

Polysaccharides from genus Ganoderma have prominent anti-aging effect,but their mechanisms are incompletely clarified.In our previous experiments,Ganoderma atrum polysaccharide(PSG)was exhibited to significantly alleviate senescence and DNA damage of A375 cells.To investigate its underlying mechanism,we conducted RNA-Seq analysis and found that PSG upregulated autophagy and mitochondria pathways compared to the model group.Further experiments showed that PSG relieved mitochondrial dysfunction via inhibiting the accumulation of reactive oxygen species(ROS)and loss of the mitochondrial membrane potential(MMP).Meanwhile,PSG activated autophagy and enhanced lysosomal function through transcription factor EB(TFEB).Interestingly,the pretreatment of autophagy inhibitors bafilomycin A1(Baf A1)reversed the ROS decline induced by PSG,which subsequently increased cellular senescence of A375.In addition,PSG had a similar anti-aging effect on normal fibroblast WI-38.Taken together,PSG might reduce ROS levels through activating autophagy,which in turn suppressed mitochondrial dysfunction and cellular senescence.