摘要
目的研究结直肠癌(CRC)中3-磷酸甘油酸脱氢酶(PHGDH)、载脂蛋白L3(APOL3)表达,分析两者对CRC患者的预后评估价值。方法回顾性收集2018年3月—2021年2月首都医科大学大兴教学医院消化内科收治的CRC患者112例临床资料。采用实时荧光定量PCR(qPCR)和免疫组织化学法检测癌组织及癌旁组织中PHGDH、APOL3 mRNA和蛋白表达;Kaplan-Meier法分析PHGDH、APOL3 mRNA表达对CRC患者生存预后的影响;Cox回归分析CRC预后的影响因素;受试者工作特征(ROC)曲线评价PHGDH、APOL3 mRNA表达水平对CRC患者预后的评估价值。结果CRC患者癌组织中PHGDH mRNA相对表达量高于癌旁组织,APOL3 mRNA相对表达量低于癌旁组织(t/P=52.982/<0.001,35.679/<0.001);CRC患者癌组织中PHGDH、APOL3蛋白阳性率分别为78.10%(90/112)、8.57%(10/112),与癌旁组织的7.62%(8/112)、76.19%(88/112)比较,差异有统计学意义(χ^(2)/P=123.722/<0.001,110.367/<0.001);TNM分期Ⅲ期、有淋巴结转移的CRC癌组织中PHGDH mRNA表达水平高于TNM分期Ⅰ~Ⅱ期、无淋巴结转移,而APOL3 mRNA表达水平低于TNM分期Ⅰ~Ⅱ期、无淋巴结转移(PHGDH:t/P=52.268/<0.001,51.315/<0.001;APOL3:t/P=15.873/<0.001,14.769/<0.001)。PHGDH mRNA高表达组3年总生存率为50.00%(26/52),低于低表达组的73.33%(44/60)(Log rankχ^(2)=4.169,P=0.041);APOL3 mRNA低表达组3年总生存率为46.30%(25/54),低于高表达组的77.59%(45/58)(Log rankχ^(2)=10.650,P=0.001)。TNM分期Ⅲ期、淋巴结转移、PHGDH mRNA高为影响CRC患者预后的独立危险因素[OR(95%CI)=1.465(1.172~1.832),1.501(1.159~1.944),1.384(1.088~1.761)],APOL3 mRNA高为独立保护因素[OR(95%CI)=0.775(0.617~0.924)];PHGDH、APOL3 mRNA表达水平及二者联合评估CRC患者预后的曲线下面积(AUC)分别为0.830、0.816、0.922,二者联合的AUC大于PHGDH、APOL3 mRNA表达水平单独评估(Z=4.482、4.130,P均<0.001)。结论CRC中PHGDH表达上调,APOL3表达下调,在CRC中均发挥重要的促癌作用,联合检测PHGDH、APOL3的表达有助于评估CRC的预后。
Objective To study the expression of 3-phosphoglycerate dehydrogenase(PHGDH)and apolipoprotein L3(APOL3)in colorectal cancer(CRC),and to analyze their prognostic value.Method A total of 112 patients with CRC admitted to the Department of Gastroenterology,Daxing Teaching Hospital of Capital Medical University from March 2018 to February 2021 were retrospectively collected.The expressions of PHGDH and APOL3 mRNA and protein in cancer tissues and adjacent tissues were detected by real-time fluorescence quantitative PCR(qPCR)and immunohistochemistry.Kaplan-Meier method was used to analyze the effect of PHGDH and APOL3 mRNA expression on the survival prognosis of CRC patients.Cox regression analysis was used to analyze the prognostic factors of CRC.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic value of PHGDH and APOL3 mRNA expression levels in CRC patients.Results The relative expression of PHGDH mRNA in cancer tissues of CRC patients was higher than that in adjacent tissues,and the relative expression of APOL3 mRNA was lower than that in adjacent tissues(t/P=52.982/<0.001,35.679/<0.001);The positive rates of PHGDH and APOL3 protein in cancer tissues of CRC patients were 78.10%(90/112)and 8.57%(10/112),respectively,compared with 7.62%(8/112)and 76.19%(88/112)in adjacent tissues,the difference was statistically significant(χ^(2)/P=123.722/<0.001,110.367/<0.001);The expression level of PHGDH mRNA in CRC tissues with TNM stage III and lymph node metastasis was higher than that in TNM stage I-II and no lymph node metastasis,while the expression level of APOL3 mRNA was lower than that in TNM stage I-II and no lymph node metastasis(t/P=52.268/<0.001,51.315/<0.001;15.873/<0.001,14.769/<0.001).The 3-year overall survival rate of PHGDH mRNA high expression group was 50.00%(26/52),which was lower than that of low expression group 73.33%(44/60)(Log rankχ^(2)=4.169,P=0.041).The 3-year overall survival rate of APOL3 mRNA low expression group was 46.30%(25/54),which was lower than that of high expression group 77.59%(45/58)(Log rankχ^(2)=10.650,P=0.001).TNM stage III,lymph node metastasis,and high PHGDH mRNA were independent risk factors affecting the prognosis of CRC patients[OR(95%CI)=1.465(1.172-1.832),1.501(1.159-1.944),1.384(1.088-1.761)],and high APOL3 mRNA was an independent protective factor[OR(95%CI)=0.775(0.617-0.924)].The area under the curve(AUC)of PHGDH,APOL3 mRNA expression levels and the combination of the two in evaluating the prognosis of CRC patients were 0.830,0.816 and 0.922,respectively.The AUC of the combination of the two was greater than that of PHGDH and APOL3 mRNA expression levels alone(Z=4.482,4.130,P<0.001).Conclusion The expression of PHGDH is up-regulated and the expression of APOL3 is down-regulated in CRC,which plays an important role in promoting cancer in CRC.The combined detection of PHGDH and APOL3 expression is helpful to evaluate the prognosis of CRC.
作者
潘艳
王蕾
洪佳
薛建波
Pan Yan;Wang Lei;Hong Jia;Xue Jianbo(Department of Gastroenterology,Daxing Teaching Hospital of Capital Medical University,Beijing 102600,China)
出处
《疑难病杂志》
CAS
2024年第10期1171-1176,共6页
Chinese Journal of Difficult and Complicated Cases
基金
北京市医院管理中心“登峰”人才培养计划项目(DFL20220101)。
