结直肠癌中PAQR3的表达水平及临床病理意义

The expression level and clinicopathologic significance of PAQR3 in colorectal cancer

目的:研究抑癌基因孕激素和脂肪Q3受体(progestin and adipo Q receptor 3,PAQR3)在结直肠癌和肠道黏膜中的表达水平及临床病理意义。方法:利用TIMER数据库比较PAQR3在泛癌种肿瘤组织与对照组织中的差别,进而收集天津医科大学总医院2002年1月至2005年12月65例结直肠癌组织标本和41例肠道黏膜组织,采用免疫组织化学染色检测PAQR3蛋白在结直肠癌组织和肠道黏膜组织中的表达,并将65例结直肠癌分为高表达组和低表达组,探讨其表达与临床病理指标之间的关系及其对患者预后的影响。采用TIMER数据库分析PAQR3表达与免疫细胞浸润的关系,c Bio Portal数据库研究PAQR3表达改变对信号转导通路的影响。结果:TIMER数据库分析显示结直肠癌中PAQR3癌组织表达低于正常对照组织,免疫组化染色显示PAQR3蛋白在65例结直肠癌组织中阳性表达率显著低于正常黏膜组织(χ^(2)=21.165,P<0.001)。32例结直肠癌高表达PAQR3,33例结直肠癌呈PAQR3低表达,PAQR3高表达与肿瘤淋巴结转移、临床分期和远处转移呈负相关(χ^(2)=4.481,P=0.034,χ^(2)=8.855,P=0.031,χ^(2)=3.972,P=0.046)。Kaplan-Meier生存分析显示结直肠癌PAQR3高表达的患者总生存和无病生存均比低表达患者好(χ^(2)=10.305,P=0.001,χ^(2)=4.135,P=0.042)。TIMER数据库分析显示PAQR3低表达与免疫细胞浸润下降相关,富集分析表明PAQR3可能通过影响机体蛋白质合成及修饰影响结直肠癌代谢过程。结论:结直肠癌组织中PAQR3蛋白表达显著降低,其低表达与结直肠癌转移和免疫浸润降低密切相关。

Objective:To investigate the expression level and clinical pathological significance of the tumor suppressor gene progestin and adipoQ receptor 3(PAQR3)in colorectal cancer and intestinal mucosa.Methods:The difference of PAQR3 in pan cancerous tumor tissues and control tissues in TIMER database was compared,and 65 human colorectal cancer tissue samples and 41 intestinal mucosa tissues from General Hospital Tianjin Medical University from January 2002 to December 2005 were collected.Immunohistochemical staining was used to detect the expression of PAQR3 protein in colorectal cancer tissues and intestinal mucosa tissues,and then 65 colorectal cancer patients were divided into high expression group and low expression group.The relationship between PAQR3 expression and clinical pathological indicators and its impact on patient prognosis was explored.Moreover,the TIMER online database was used to analyze the relationship between PAQR3 expression and immune cell infiltration,and the cBioPortal database was used to investigate the impact of changes in PAQR3 expression on signal transduction pathways.Results:TIMER database analysis showed that the expression of PAQR3 in colorectal cancer tissue was lower than that in normal control tissue.Immunohistochemical staining showed that the positive expression rate of PAQR3 protein in 65 cases of colorectal cancer tissue was significantly lower than that in normal mucosal tissue(χ^(2)=21.165,P<0.001).32 cases of colorectal cancer showed high expression of PAQR3,while 33 cases showed low expression of PAQR3.High expression of PAQR3 in colorectal cancer was negatively correlated with tumor lymph node metastasis,clinical stage,and distant metastasis(χ^(2)=4.481,P=0.034,χ^(2)=8.855,P=0.031,χ^(2)=3.972,P=0.046).Kaplan-Meier survival analysis showed that patients with high expression of PAQR3 in colorectal cancer had better overall survival and disease-free survival compared to patients with low expression(χ^(2)=10.305,P=0.001,χ^(2)=4.135,P=0.042).TIMER database analysis showed that low expression of PAQR3 was associated with decreased immune cell infiltration.The enrichment analysis results indicated that PAQR3 might affect the metabolic process of colorectal cancer by affecting protein synthesis and modification processes.Conclusion:The expression of PAQR3 protein is significantly reduced in colorectal cancer tissue,and its low expression is closely related to the decrease in metastasis and immune infiltration of colorectal cancer.