Expression And Clinical Significance Of Obg-like ATPase 1 In Inflammatory Bowel Disease

Background Obg-like ATPase 1(OLA1),a negative regulator of cellular antioxidant response independent of transcription.It is reported that OLA1 plays an important role in the development of colon cancer.Whether OLA1 plays a role in the development of inflammatory bowel disease(IBD)– one of the precancerous lesions of colorectal cancer – is unclear.Methods Data from the Second Affiliated Hospital of Zhejiang University between 2015 and2017 were evaluated.The study consisted of 62 patients with IBD.Diagnosis-to-surgery time(DST)was defined as the time from the initial diagnosis to surgery.Univariate and multivariate Cox regression analysis were used to evaluate the relationship between clinicopathological variables and DST.Surgical samples were analyzed by immunohistochemistry to determine the expression of OLA1 and non-parametric Marginal Homogeneity test of paired samples was used to compare the differences.The correlation between OLA1 and other clinicopathological variables was analyzed using Spearman's correlation analysis.A two-tailed p-value <0.05 was considered statistically significant.Intestinal-specific OLA1 knockout mice were constructed by Cre-Loxp technique,and then polymerase chain reaction(PCR)was used to verify the genotype.Results1.Based on univariate Cox regression analysis,age,sex and body mass index were associated with DST of Crohn's disease(CD)patients.On multivariate Cox regression analysis: CD patients who were ?35 years old(compared to <35 years old: hazard ratio [HR],0.368;95% confidence interval [CI],0.179-0.756;p=0.007)and with a body mass index ?18.5 kg/m2(compared to <18.5 kg/m2: HR,0.485;95% CI,0.257-0.915;p=0.025)had longer DST;Male patients(compared to female: HR,2.248;95% CI,1.127-4.483;p=0.021).2.OLA1 expression increased in the inflamed intestinal epithelial cells of patients with IBD(Marginal Homogeneity test,p=0.015).Among the CD patients with the inflamed intestinal epithelial cells OLA1-positive expression,there were more younger patients(<35 years old),accounting for 70%(p=0.032).3.OLA1 expression of the inflamed intestinal epithelial cells was negatively correlated with erythrocyte sedimentation rate(ESR)(Spearman's correlation analysis,correlation coefficient=-0.312,p=0.015).4.The intestinal-specific OLA1 knockout mice were successfully constructed,preparing for the establishment IBD mice.Conclusions1.OLA1 may be related to the pathogenesis of IBD,but have no correlation with the progression of IBD.2.The intestinal-specific OLA1 knockout mice were constructed preparing for the further exploration of the development of IBD or even IBD-associated colorectal cancer(IBD-CRC)in vivo.