Expression And Clinical Significance Of Absent In Melanoma 2 In Colorectal Cancer

Objective: Absent in melanoma 2(AIM2)is a newly discovered inflammasome in recent years,recent studies have shown that AIM2 is associated with infection defense,which may play a key role in the pathogenesis of cancer.In this study,the expression levels of the AIM2 were determined in colorectal cancer cell lines and colorectal cancer tissues.We discussed the potential relationships between AIM2 expression and clinicopathological characteristics,survival prognosis in colorectal cancer.Moreover,we investigate the value of combination detection of expression of AIM2 and the preoperative carcinoembryonic antigen(CEA)level for the prognosis of CRC patients,to provide theoretical basis for individualized treatment and prognosis analysis of colorectal cancer.Methods:(1)we first used western blotting and quantitative RT-PCR(q RT-PCR)to detect the protein and m RNA expression of AIM2 in seven CRC cell lines(SW480,SW620,Km12,Lovo,HCT116,RKO and CCL244).Then,we examined AIM2 expression in 18 randomly selected pairs of colorectal cancer tumors(T)and adjacent normal tissues(N)using western blotting.(2)Besides,we detected the expression of AIM2 protein in the 142 primary colorectal cancer tissues and 41 adjacent normal colorectal tissue specimens by immunohistochemical staining to evaluate its clinicopathologic characteristics and survival prognosis in colorectal cancer.(3)Lastly,the preoperative serum levels of CEA of 142 patients were collected.Spearman analysis to examine the correlation between the expression of AIM2 and preoperative serum CEA levels in colorectal cancer.Then,we used Kaplan-Meier method to analyze the survival rate.we investigate the value of combination detection of expression of AIM2 and the preoperative CEA level for the prognosis of colorectal cancer patients.Results:(1)The results by q RT-PCR and Western blot showed that the protein and m RNA expression of AIM2 were low in most of the colorectal cancer cell lines.In 18 randomly selected pairs of colorectal cancer tumors(T)and adjacent normal tissues(N),our Western blot results indicated that AIM2 expression was obviously lower in the primary colorectal cancer tissues than adjacent normal tissues(P<0.01).(2)IHC results displayed that AIM2 expressed more lowly in the tumor tissues(32.4%)than in the tumor-adjacent normal tissues(80.5%)(P<0.001).AIM2 expression is significantly correlated with depth of invasion,TNM stage and lymph node metastasis(all P<0.05).Kaplan-Meier curves revealed that the low AIM2 expression group had a significantly shorter overall survival rate than the high AIM2 expression group(P=0.001).Cox proportional hazards model identified that AIM2 expression is an independent prognostic factor for survival.(3)The preoperative positive rate of serum CEA of 142 colorectal cancer patients was 41.5%,and there was a negative correlation between AIM2 expression and CEA levels in colorectal cancer tissue(r=-0.217,P=0.009).when combinated detection of AIM2 and preoperative CEA,the Kaplan-Meier survival curve highlights considerable differences between the four Phenotypes(AIM2+/CEA-,AIM2+/CEA+,AIM2-/CEA+,AIM2-/CEA-)with AIM2-/CEA+ tumours having significantly worsened survival time compared to AIM2+/CEA-tumours(P<0.001).Conclusion: The expression of AIM2 is downregulated in colorectal cancer tissues and most of colorectal cancer cell lines.AIM2 expression is associated with TNM stage,depth of invasion and lymph node metastasis.AIM2 expression is an independent prognostic factor for survival,and its low expression is closely associated with poor survival in colorectal cancer patients.Moreover,combination detection of AIM2 expression and preoperative serum CEA levels has some advantages in the estimation the prognosis of colorectal cancer.AIM2 might serve as a novel prognostic marker,and which may present a potential therapeutic target for colorectal cancer.