TNFAIP3基因遗传变异对食管鳞癌患者预后的影响
|
摘要
目的:探讨重组人肿瘤坏死因子α诱导蛋白3(TNFAIP3)基因的遗传变异对食管鳞癌(ESCC)患者预后的影响。方法:本研究纳入175例食管鳞癌根治术患者。在手术前收集患者的外周血5 m L用来提取基因组DNA,对rs583522位点进行基因分型,并对基因型和基线临床资料,以及患者的长期预后情况进行关联性分析。结果:野生型AA型相对于AG/GG型患者者来说具有明显较晚的肿瘤分期(P<0.001)。AA型的患者更容易复发(P=0.022)。生存分析结果表明AA型患者相对于AG/GG型患者具有明显较差的总生存期(OS),两种基因型患者的中位OS分别为38.2和48.5个月(P=0.017)。结论:TNFAIP3多态性位点rs583522可能通过影响了该基因的功能,进而使得不同基因型的ESCC患者具有不同的恶性程度。因此TNFAIP3基因rs583522位点可以作为评价食管鳞癌患者预后的生物标记物。
AIM:To investigate the influence of genetic variation of tumor necrosis factor alpha induced protein 3(TNFAIP3) on prognosis among esophageal squamous cell carcinoma patients.METHODS:A total of 175 patients underwent complete surgical resection of esophageal squamous cell carcinoma were included in this study.5 m L peripheral blood specimen of the patient was collected.Genomic DNA were extracted and genotype of rs583522 were analyzed.The association between genotype and baseline clinical characteristics and prognosis were analyzed.RESULTS:Wild type AA genotypes showed advanced tumor stages compared with those of homozygous G-allele carriers(P <0.001).Patients with an AA genotype were significantly more likely to experience relapse(P =0.022).Survival analysis revealed a significant difference in overall survival between different genotype groups(P = 0.017).CONCLUSION:rs583522 genotypes can be used as biomarkers to evaluate the prognosis of patients with esophageal squamous carcinoma.
AIM:To investigate the influence of genetic variation of tumor necrosis factor alpha induced protein 3(TNFAIP3) on prognosis among esophageal squamous cell carcinoma patients.METHODS:A total of 175 patients underwent complete surgical resection of esophageal squamous cell carcinoma were included in this study.5 m L peripheral blood specimen of the patient was collected.Genomic DNA were extracted and genotype of rs583522 were analyzed.The association between genotype and baseline clinical characteristics and prognosis were analyzed.RESULTS:Wild type AA genotypes showed advanced tumor stages compared with those of homozygous G-allele carriers(P <0.001).Patients with an AA genotype were significantly more likely to experience relapse(P =0.022).Survival analysis revealed a significant difference in overall survival between different genotype groups(P = 0.017).CONCLUSION:rs583522 genotypes can be used as biomarkers to evaluate the prognosis of patients with esophageal squamous carcinoma.
引文
[1]Naik KB,Liu Y,Goodman M,et al.Concurrent chemoradiotherapy with or without surgery for patients with resectable esophageal cancer:An analysis of the National Cancer Data Base[J].Cancer,2017,123(18):3476-3485.
[2]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-32.
[3]Liang H,Fan JH,Qiao YL.Epidemiology,etiology,and prevention of esophageal squamous cell carcinoma in China[J].Cancer Biol Med,2017,14(1):33-41.
[4]Peerlings J,Van De Voorde L,Mitea C,et al.Hypoxia and hypoxia response-associated molecular markers in esophageal cancer:A systematic review[J].Methods,2017,130:51-62.
[5]Yang Y,Jia J,Sun Z,et al.Prognosis impact of clinical characteristics in patients with inoperable esophageal squamous cell carcinoma[J].PLo S One,2017,12(8):e0182660.
[6]Chang JS,Hsiao JR,Chen CH.ALDH2 polymorphism and alcohol-related cancers in Asians:a public health perspective[J].J Biomed Sci,2017,24(1):19.
[7]Shimane K,Kochi Y,Horita T,et al.The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population[J].Arthritis Rheum,2010,62(2):574-579.
[8]Jallades L,Baseggio L,Sujobert P,et al.Exome sequencing identifies recurrent BCOR gene alterations and the absence of KLF2,TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma[J].Haematologica,2017,102(10):1758-1766.
[9]Osako M,Itsumi M,Yamaguchi H,et al.A20 restores phorbol ester-induced differentiation of THP-1 cells in the absence of nuclear factor-kappa B activation[J].J Cell Biochem,2018,119(2):1475-1487.
[10]Ghadban T,Schmidt-Yang M,Uzunoglu FG,et al.An A/C germline single-nucleotide polymorphism in the TNFAIP3 gene is associated with advanced disease stage and survival in only surgically treated esophageal cancer[J].J Hum Genet,2014,59(12):661-666.
[11]Plant D,Prajapati R,Hyrich KL,et al.Replication of association of the PTPRC gene with response to antitumor necrosis factor therapy in a large UK cohort[J].Arthritis Rheum,2012,64(3):665-670.
[12]Takahashi Y,Sugimachi K,Yamamoto K,et al.Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14[J].Cancer Sci,2017,108(11):2239-2247.
[13]Tang H,Wei P,Chang P,et al.Genetic polymorphisms associated with pancreatic cancer survival:a genome-wide association study[J].Int J Cancer,2017,141(4):678-686.
[14]Foti A,Dorendorf F,Leimkuhler S.Single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase[J].PLo S One,2017,12(7):e0182061.
[15]Zhang X,Yin JF,Zhang J,et al.UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia:a systematic review and meta-analysis[J].Cancer Chemother Pharmacol,2017,80(1):135-149.
[16]楼江,林能明,王刚,等.吉西他滨的核苷酸转运体基因组学研究[J].中国临床药理学与治疗学,2016,22(5):586-594.
[17]Ghadban T,Schmidt-Yang M,Uzunoglu FG,et al.Evaluation of the germline single nucleotide polymorphism rs583522 in the TNFAIP3 gene as a prognostic marker in esophageal cancer[J].Cancer Genet,2015,208(12):595-601.
[18]Lurje G,Leers JM,Pohl A,et al.Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus[J].Ann Surg,2010,251(5):857-864.
[19]Adrianto I,Wen F,Templeton A,et al.Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus[J].Nat Genet,2011,43(3):253-258.
[2]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-32.
[3]Liang H,Fan JH,Qiao YL.Epidemiology,etiology,and prevention of esophageal squamous cell carcinoma in China[J].Cancer Biol Med,2017,14(1):33-41.
[4]Peerlings J,Van De Voorde L,Mitea C,et al.Hypoxia and hypoxia response-associated molecular markers in esophageal cancer:A systematic review[J].Methods,2017,130:51-62.
[5]Yang Y,Jia J,Sun Z,et al.Prognosis impact of clinical characteristics in patients with inoperable esophageal squamous cell carcinoma[J].PLo S One,2017,12(8):e0182660.
[6]Chang JS,Hsiao JR,Chen CH.ALDH2 polymorphism and alcohol-related cancers in Asians:a public health perspective[J].J Biomed Sci,2017,24(1):19.
[7]Shimane K,Kochi Y,Horita T,et al.The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population[J].Arthritis Rheum,2010,62(2):574-579.
[8]Jallades L,Baseggio L,Sujobert P,et al.Exome sequencing identifies recurrent BCOR gene alterations and the absence of KLF2,TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma[J].Haematologica,2017,102(10):1758-1766.
[9]Osako M,Itsumi M,Yamaguchi H,et al.A20 restores phorbol ester-induced differentiation of THP-1 cells in the absence of nuclear factor-kappa B activation[J].J Cell Biochem,2018,119(2):1475-1487.
[10]Ghadban T,Schmidt-Yang M,Uzunoglu FG,et al.An A/C germline single-nucleotide polymorphism in the TNFAIP3 gene is associated with advanced disease stage and survival in only surgically treated esophageal cancer[J].J Hum Genet,2014,59(12):661-666.
[11]Plant D,Prajapati R,Hyrich KL,et al.Replication of association of the PTPRC gene with response to antitumor necrosis factor therapy in a large UK cohort[J].Arthritis Rheum,2012,64(3):665-670.
[12]Takahashi Y,Sugimachi K,Yamamoto K,et al.Japanese genome-wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14[J].Cancer Sci,2017,108(11):2239-2247.
[13]Tang H,Wei P,Chang P,et al.Genetic polymorphisms associated with pancreatic cancer survival:a genome-wide association study[J].Int J Cancer,2017,141(4):678-686.
[14]Foti A,Dorendorf F,Leimkuhler S.Single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase[J].PLo S One,2017,12(7):e0182061.
[15]Zhang X,Yin JF,Zhang J,et al.UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia:a systematic review and meta-analysis[J].Cancer Chemother Pharmacol,2017,80(1):135-149.
[16]楼江,林能明,王刚,等.吉西他滨的核苷酸转运体基因组学研究[J].中国临床药理学与治疗学,2016,22(5):586-594.
[17]Ghadban T,Schmidt-Yang M,Uzunoglu FG,et al.Evaluation of the germline single nucleotide polymorphism rs583522 in the TNFAIP3 gene as a prognostic marker in esophageal cancer[J].Cancer Genet,2015,208(12):595-601.
[18]Lurje G,Leers JM,Pohl A,et al.Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus[J].Ann Surg,2010,251(5):857-864.
[19]Adrianto I,Wen F,Templeton A,et al.Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus[J].Nat Genet,2011,43(3):253-258.