解整合素-金属蛋白酶33基因多态性与胆管癌及血清肿瘤标志物水平的相关性研究

Association of disintegrin-metalloproteinase 33 gene polymorphisms with cholangiocarcinoma and serum tumor marker levels

背景胆管癌(cholangiocarcinoma,CC)是发源于胆管上皮细胞的恶性肿瘤,由于起病隐匿,预后较差,尚缺乏有效根治手段.解整合素-金属蛋白酶(disintegrin and metalloproteinase,ADAM)33在肿瘤、炎症的发生发展中发挥重要作用.本研究观察了C ADAM33 rs678881及rs2853209与CC的易感性的关系.目的探讨ADAM33基因rs678881、rs2853209单核苷酸多态性(single nucleotide polymorphism,SNP)与胆管癌的易感性的关系.方法选取2017-01/2020-06期间于我院诊治的胆管癌手术患者212例作为研究组,以同期在我院体检的健康查体者186例作为对照组,采用聚合酶链反应-限制性片段长度多态性法检测研究对象血清中ADAM33基因rs678881及rs2853209位点的基因型,采用酶联免疫吸附法检测血清可溶性细胞间分子-1(soluble intercellular molecule-1,sICAM-1)水平,电化学发光法检测血清癌胚抗原(carcinoembryonic antigen,CEA)、癌细胞表面抗原(cancer cell surface antigen,CA19-9)水平.结果研究组的ADAM33 rs678881 GC及rs678881 CC的基因分布频率较对照组高(P<0.05).研究组的ADAM33 rs678881C等位基因分布频率较对照组高(P<0.05).研究组与对照组在ADAM33 rs2853209的基因多态性方面比较无显著性差异.研究组患者CA19-9、sICAM-1及CEA水平显著高于对照组,差异具有统计学意义(P<0.05).ADAM33 rs678881GG、GC、CC基因型患者的CA19-9、sICAM-1及CEA水平依次升高,各基因型之间水平比较差异具有统计学意义(P<0.05).结论ADAM33 rs678881 GC、CC基因型及C等位基因增加胆管癌的易感性及血清肿瘤标志物的水平,并可能参与了疾病的进展.

BACKGROUND Cholangiocarcinoma(CC)is a malignant tumor originating from bile duct epithelial cells.Due to its insidious onset and poor prognosis,effective radical treatment is still lacking.Disintegrin and metalloproteinase(ADAM)33 plays an important role in the occurrence and development of tumors and inflammation.The relationship between the ADAM33 gene polymorphisms rs678881 and rs2853209 and susceptibility to CC remains to be investigated.AIM To investigate the relationship between the ADAM33 gene single nucleotide polymorphisms(SNPs)rs678881 and rs2853209 and susceptibility to CC.METHODS Two hundred and twelve patients undergoing surgery for CC at our hospital from January 2021 to June 2022 were selected as a study group,and 186 healthy cases who underwent physical examination at our hospital during the same period were selected as a control group.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of ADAM33 gene rs678881 and rs2853209.Serum sICAM-1 level was detected by enzyme-linked immunosorbent assay,and serum carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels were detected by electrochemiluminescence method.RESULTS The gene distribution frequency of ADAM33 rs678881 GC and rs678881 CC in the study group was higher than that of the control group(P<0.05).The frequency of ADAM33 rs678881 C allele distribution in the study group was also higher than that of the control group(P<0.05).There was no significant difference between the study group and the control group in the genetic polymorphism of ADAM33 rs2853209(P>0.05).The levels of CA19-9,sICAM-1,and CEA in the study group were significantly higher than those of the control group(P<0.05).The levels of CA19-9,sICAM-1,and CEA in patients with ADAM33 rs678881GG,GC,and CC genotypes increased sequentially,and the differences in their levels between the genotypes were statistically significant(P<0.05).CONCLUSION ADAM33 rs678881 GC and CC genotypes and C allele increase the susceptibility to CC and the levels of serum tumor markers,and may be related to the progression of the disease.