结直肠癌组织中PPAT的水平及临床意义

Level and clinical significance of PPAT in colorectal cancer tissues

目的探讨结直肠癌组织中磷酸核糖焦磷酸酰胺转移酶(PPAT)的水平及临床意义。方法基于TIMER、GEPIA和UALCAN数据库分析PPAT在结直肠癌组织和正常组织之间的表达差异,采用实时定量PCR检测105对结直肠癌组织和癌旁组织的PPAT水平及其与结直肠癌临床病理特征和预后的关系,TIMER数据库探讨PPAT在结直肠癌中的表达与免疫浸润水平的相关性。结果TIMER、GEPIA和UALCAN数据库分析结果均发现,结直肠癌的PPAT水平高于正常组织,差异有统计学意义(P<0.05);利用qPCR验证发现,癌组织的PPAT水平为5.287±1.996,高于癌旁组织的1.392±0.751,差异有统计学意义(P<0.05);ROC曲线显示组织PPAT水平诊断结直肠癌的曲线下面积分别为0.958(95%CI:0.932~0.985),以2.931为参考值时对应的约登指数最大,灵敏度分别为86.67%,特异度为97.14%。组织PPAT水平与性别、年龄、家族史、部位和T分期无关(P>0.05),而与分化程度、淋巴结转移、肿瘤大小和TNM分期有关(P<0.05)。PPAT低水平者的中位总生存期为50.0个月,优于高水平者的45.5个月(HR=4.123,95%CI:1.952~6.245,P<0.001),经多因素分析显示PPAT水平升高是结直肠癌患者预后不良的独立危险因素(HR=3.245,95%CI:1.754~5.012,P=0.013)。结肠癌中PPAT水平与B细胞、CD8+T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润呈显著正相关(P<0.05),而与CD4+T细胞的浸润无关(P>0.05);直肠癌中PPAT水平与CD8+T细胞、中性粒细胞的浸润呈显著正相关(P<0.05),而与B细胞、CD4+T细胞、巨噬细胞和树突状细胞的浸润无关(P>0.05)。结论PPAT可能是结直肠癌的一种潜在的新的预后标志物,PPAT过度表达可能参与CRC的能量代谢和免疫浸润调节。

Objective To investigate the the level and clinical significance of phosphoribosyl pyrophosphate amidotransferase(PPAT)in colorectal cancer tissues.Methods Based on TIMER,GEPIA and UALCAN databases,the expression differences of PPAT between colorectal cancer tissues and normal tissues were analyzed.Real-time quantitative PCR was used to detect PPAT levels in 105 pairs of colorectal cancer tissues and adjacent tissues,and their relationship with clincopathological characteristics and prognosis of colorectal cancer were analyzed.The TIMER database was used to explore the correlation between PPAT expression and immune infiltration levels in colorectal cancer.Results The results of TIMER,GEPIA and UALCAN database analysis showed that the PPAT levels in colorectal cancer tissues were higher than those in normal tissues,with a statistically significant difference(P<0.05).Using qPCR validation,it was found that the PPAT level in cancer tissues was higher than that in adjacent tissues(5.287±1.996 vs.1.392±0.751),with a statistically significant difference(P<0.05).The ROC curve shows that the area under the curve for diagnosing colorectal cancer at the tissue PPAT level was 0.958(95%CI:0.932-0.985),and when 2.931 was used as reference values,the corresponding Jordan index was the highest,with sensitivity of 86.67%and specificity of 97.14%,respectively.The tissue PPAT level was not related to gender,age,family history,location and T stage(P>0.05),but was related to the degree of differentiation,lymph node metastasis,tumor size and TNM stage(P<0.05).The median overall survival of patients with low level of PPAT was 50.0 months,which was better than 45.5 months of those with high level(HR=4.123,95%CI:1.952-6.245,P<0.001).Multivariate analysis showed that elevated PPAT levels were an independent risk factor for poor prognosis in colorectal cancer patients(HR=3.245,95%CI:1.754-5.012,P=0.013).PPAT level in colon cancer was significantly positively correlated with the infiltration of B cells,CD8+T cells,macrophages,neutrophils and dendritic cells(P<0.05),but not with the infiltration of CD4+T cells(P>0.05).PPAT levels in rectal cancer were significantly positively correlated with the infiltration of CD8+T cells and neutrophils(P<0.05),but not with the infiltration of B cells,CD4+T cells,macrophages and dendritic cells(P>0.05).Conclusion PPAT is highly expressed in colorectal cancer and has certain value in the diagnosis,disease prediction and prognosis evaluation of the tumor.