结直肠腺癌、腺瘤组织及正常组织中黑色素瘤缺乏因子2表达差异的研究
|
摘要
目的通过免疫组化方法比较结直肠癌患者的癌组织、腺瘤组织、癌旁正常组织及单纯结直肠腺瘤患者的腺瘤组织中黑色素瘤缺乏因子2(AIM2)基因的表达差异。方法收集结直肠癌合并肠道息肉的患者,每例患者手术切除标本中均同时有腺癌病灶及独立的腺瘤病灶。同时收集单纯结直肠腺瘤患者,均通过门诊内镜或外科手术获取腺瘤组织标本。对样本进行AIM2蛋白免疫组化染色(En Vision法),对比分析不同的样本组织间AIM2表达情况。结果研究纳入的52例腺癌合并腺瘤的结直肠癌患者,获取癌组织、腺瘤组织及癌旁正常组织标本各52份,纳入78例结直肠腺瘤患者,获取单纯腺瘤标本78例。秩和检验发现,AIM2基因的表达情况,结直肠癌患者的正常组织中最强(秩均值151. 37),单纯结直肠腺瘤患者的腺瘤组织次之(秩均值121. 88),结直肠癌患者的腺瘤组织再次之(秩均值103. 11),结直肠癌患者的癌组织中AIM2表达最弱(秩均值91. 45),差异有统计学意义(χ~2=26. 048,P <0. 01)。结论 AIM2在正常组织、腺瘤组织、腺癌组织中的表达逐步下调,提示AIM2可能是一种抑癌基因,它的缺失,可能导致结直肠肿瘤的发生及进展。
Objective To compare the expression of absent in melanoma2( AIM2) gene in cancer tissues,adenoma tissues,adjacent normal tissues and colorectal adenomas by immunohistochemistry.Methods Patients with colorectal cancer and intestinal polyps were enrolled.Each patient had an adenocarcinoma lesion and an independent adenoma lesion in the surgical resection specimen.At the same time,patients with simple colorectal adenoma were collected,and adenoma tissue specimens were obtained by outpatient endoscopy or surgery.Immunohistochemical staining( En Vision method) of AIM2 protein was performed and the expression of AIM2 in different samples was compared and analyzed. Results A total of 52 patients with colorectal cancer with adenocarcinoma and adenoma were enrolled,and 52 specimens of cancer,adenoma and adjacent normal tissues were obtained. Seventy-eight patients with colorectal adenoma were enrolled and a simple adenoma specimen was obtained.The rank sum test found that the expression of AIM2 gene was the strongest in normal tissues of patients with colorectal cancer( rank average = 151. 37),followed by adenoma tissue in patients with colorectal adenoma( rank average = 121. 88),and adenoma tissue in patients with colorectal cancer( rank average = 103. 11) while AIM2 expression was the weakest in cancer tissues of patients with colorectal cancer( rank average = 91. 45)( χ~2= 26. 048,P < 0. 01).Conclusion The expression of AIM2 in normal tissues,adenoma tissues and adenocarcinoma tissues is gradually down-regulated.This suggests that AIM2 may be a tumor suppressor gene,and its deletion may lead to the occurrence and progression of colorectal tumors.
Objective To compare the expression of absent in melanoma2( AIM2) gene in cancer tissues,adenoma tissues,adjacent normal tissues and colorectal adenomas by immunohistochemistry.Methods Patients with colorectal cancer and intestinal polyps were enrolled.Each patient had an adenocarcinoma lesion and an independent adenoma lesion in the surgical resection specimen.At the same time,patients with simple colorectal adenoma were collected,and adenoma tissue specimens were obtained by outpatient endoscopy or surgery.Immunohistochemical staining( En Vision method) of AIM2 protein was performed and the expression of AIM2 in different samples was compared and analyzed. Results A total of 52 patients with colorectal cancer with adenocarcinoma and adenoma were enrolled,and 52 specimens of cancer,adenoma and adjacent normal tissues were obtained. Seventy-eight patients with colorectal adenoma were enrolled and a simple adenoma specimen was obtained.The rank sum test found that the expression of AIM2 gene was the strongest in normal tissues of patients with colorectal cancer( rank average = 151. 37),followed by adenoma tissue in patients with colorectal adenoma( rank average = 121. 88),and adenoma tissue in patients with colorectal cancer( rank average = 103. 11) while AIM2 expression was the weakest in cancer tissues of patients with colorectal cancer( rank average = 91. 45)( χ~2= 26. 048,P < 0. 01).Conclusion The expression of AIM2 in normal tissues,adenoma tissues and adenocarcinoma tissues is gradually down-regulated.This suggests that AIM2 may be a tumor suppressor gene,and its deletion may lead to the occurrence and progression of colorectal tumors.
引文
[1]De Young KL,Ray ME,Su YA,et al.Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma[J].Oncogene,1997,15(4):453-457.
[2]Man SM,Zhu Q,Zhu L,et al.Critical Role for the DNA Sensor AIM2in Stem Cell Proliferation and Cancer[J]. Cell,2015,162(1):45-58.
[3]Wilson JE,Petrucelli AS,Chen L,et al.Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt[J].Nat Med,2015,21(8):906-913.
[4] Ponomareva L,Liu H,Duan X,et al. AIM2,an IFN-inducible cytosolic DNA sensor,in the development of benign prostate hyperplasia and prostate cancer[J]. Mol Cancer Res,2013,11(10):1193-1202.
[5] Wang LJ,Hsu CW,Chen CC,et al. Interactome-wide analysis identifies end-binding protein 1 as a crucial component for the specklike particle formation of activated absence in melanoma 2(AIM2)inflammasomes[J].Mol Cell Proteomics,2012,11(11):1230-1244.
[6]Chen LC,Wang LJ,Tsang NM,et al.Tumour inflammasome-derived IL-1beta recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma[J]. EMBO Mol Med,2012,4(12):1276-1293.
[7]Kondo Y,Nagai K,Nakahata S,et al.Overexpression of the DNA sensor proteins,absent in melanoma 2 and interferon-inducible 16,contributes to tumorigenesis of oral squamous cell carcinoma with p53inactivation[J].Cancer Sci,2012,103(4):782-790.
[8]Kong H,Wang Y,Zeng X,et al.Differential expression of inflammasomes in lung cancer cell lines and tissues[J]. Tumour Biol,2015,36(10):7501-13.
[9]Dihlmann S,Tao S,Echterdiek F,et al.Lack of Absent in Melanoma2(AIM2)expression in tumor cells is closely associated with poor survival in colorectal cancer patients[J]. Int J Cancer,2014,135(10):2387-2396.
[10]Patsos G,Germann A,Gebert J,et al.Restoration of absent in melanoma 2(AIM2)induces G2/M cell cycle arrest and promotes invasion of colorectal cancer cells[J]. Int J Cancer,2010,126(8):1838-1849.
[11]程丽,程莉,贾丹丹,等.结直肠腺瘤发生相关因素的研究进展[J].医学综述,2014,20(10):1790-1792.
[12]Al-Kharusi MR,Smartt HJ,Greenhough A,et al.LGR5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2:implications for targeting adenoma stem cells with NSAIDs[J].Carcinogenesis,2013,34(5):1150-1157.
[13]张志,杨晓东,孙亮,等.结直肠癌组织AIM2和血清CEA表达与预后相关性分析[J].中华肿瘤防治杂志,2018,25(01):20-25+33.
[14]Lasry A,Zinger A,Ben-Neriah Y.Inflammatory networks underlying colorectal cancer[J].Nat Immunol,2016,17(3):230-240.
[15]Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow[J].Lancet,2001,357(9255):539-545.
[16]林三仁,李渊.加强炎症在肿瘤发生发展中作用的研究[J].中华内科杂志,2014,53(5):345-346.
[2]Man SM,Zhu Q,Zhu L,et al.Critical Role for the DNA Sensor AIM2in Stem Cell Proliferation and Cancer[J]. Cell,2015,162(1):45-58.
[3]Wilson JE,Petrucelli AS,Chen L,et al.Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt[J].Nat Med,2015,21(8):906-913.
[4] Ponomareva L,Liu H,Duan X,et al. AIM2,an IFN-inducible cytosolic DNA sensor,in the development of benign prostate hyperplasia and prostate cancer[J]. Mol Cancer Res,2013,11(10):1193-1202.
[5] Wang LJ,Hsu CW,Chen CC,et al. Interactome-wide analysis identifies end-binding protein 1 as a crucial component for the specklike particle formation of activated absence in melanoma 2(AIM2)inflammasomes[J].Mol Cell Proteomics,2012,11(11):1230-1244.
[6]Chen LC,Wang LJ,Tsang NM,et al.Tumour inflammasome-derived IL-1beta recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma[J]. EMBO Mol Med,2012,4(12):1276-1293.
[7]Kondo Y,Nagai K,Nakahata S,et al.Overexpression of the DNA sensor proteins,absent in melanoma 2 and interferon-inducible 16,contributes to tumorigenesis of oral squamous cell carcinoma with p53inactivation[J].Cancer Sci,2012,103(4):782-790.
[8]Kong H,Wang Y,Zeng X,et al.Differential expression of inflammasomes in lung cancer cell lines and tissues[J]. Tumour Biol,2015,36(10):7501-13.
[9]Dihlmann S,Tao S,Echterdiek F,et al.Lack of Absent in Melanoma2(AIM2)expression in tumor cells is closely associated with poor survival in colorectal cancer patients[J]. Int J Cancer,2014,135(10):2387-2396.
[10]Patsos G,Germann A,Gebert J,et al.Restoration of absent in melanoma 2(AIM2)induces G2/M cell cycle arrest and promotes invasion of colorectal cancer cells[J]. Int J Cancer,2010,126(8):1838-1849.
[11]程丽,程莉,贾丹丹,等.结直肠腺瘤发生相关因素的研究进展[J].医学综述,2014,20(10):1790-1792.
[12]Al-Kharusi MR,Smartt HJ,Greenhough A,et al.LGR5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2:implications for targeting adenoma stem cells with NSAIDs[J].Carcinogenesis,2013,34(5):1150-1157.
[13]张志,杨晓东,孙亮,等.结直肠癌组织AIM2和血清CEA表达与预后相关性分析[J].中华肿瘤防治杂志,2018,25(01):20-25+33.
[14]Lasry A,Zinger A,Ben-Neriah Y.Inflammatory networks underlying colorectal cancer[J].Nat Immunol,2016,17(3):230-240.
[15]Balkwill F,Mantovani A.Inflammation and cancer:back to Virchow[J].Lancet,2001,357(9255):539-545.
[16]林三仁,李渊.加强炎症在肿瘤发生发展中作用的研究[J].中华内科杂志,2014,53(5):345-346.