Twist基因在结肠癌中的表达分析
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摘要
目的:检测结肠癌组织中Twist基因的表达情况,探讨Twist基因表达与结肠癌肿瘤分化程度,浸润深度,淋巴结转移、远处转移及TNM分期等临床病理指标之间的关系,进而了解其在结肠癌组织发生、发展过程中的表达规律。
方法:收集结肠癌手术切除标本50例,分别切取结肠癌和切端结肠组织;采用实时定量PCR检测50例结肠癌及切端结肠组织Twist基因的mRNA转录水平;运用免疫组织化学(SABC)法检测50例结肠癌及切端结肠组织Twist蛋白的表达水平;结合临床病理资料,进行统计学分析。
结果:
1.结肠癌组织Twist基因mRNA转录水平高于切端结肠组织,差异有统计学意义(P＜0.05),结肠癌组织Twist基因mRNA的转录水平在不同的肿瘤分化程度、浸润深度、淋巴结转移、远处转移及TNM分期之间的差异有统计学意义(P＜0.05),在不同的年龄、性别及病理类型之间差异无统计学意义(P＞0.05)。
2.结肠癌、切端结肠组织中Twist蛋白表达阳性率分别为68%和16%,Twist蛋白在结肠癌组织的表达水平高于切端结肠组织,差异有统计学意义(P＜0.05),结肠癌组织Twist的蛋白表达水平在肿瘤的分化程度、浸润程度、淋巴结转移、远处转移及TNM分期间的差异有统计学意义(P＜0.05),在不同的年龄、性别及病理类型之间差异无统计学意义(P＞0.05)。
3.结肠癌组织Twist的mRNA转录水平与蛋白表达水平存在正相关(P＜0.05)。
结论:
1.Twist基因高表达是结肠癌发生、发展的重要分子事件之一,其参与了结肠癌的恶性转化过程。
2.结肠癌组织Twist mRNA转录水平与蛋白表达水平呈正相关,表明作为转录调控因子的Twist基因的活化是不仅在mRNA的转录水平,而且其最终能翻译成Twist蛋白而发挥其生物学特性。
3.结肠癌组织Twist基因的表达在不同肿瘤的分化程度、浸润深度、淋巴结转移、远处转移及TNM分期之间存在着显著差异,这提示Twist基因在结肠癌侵袭、转移的生物学过程中发挥着一定作用,在一定程度上可作为检测恶性肿瘤进展的生物学指标之一。
4.结肠癌组织Twist基因的高表达提示Twist基因在结肠癌的形成、发展中起重要的促进作用,对Twist基因表达的抑制将可能对肿瘤的生长和转移起到一定的遏制作用,下调Twist的表达可能成为恶性肿瘤基因治疗的一个新的靶点。
Objective:To detect the expression of Twist gene in colon carcinoma tissue and study the association of the changs in tumor differentiation,invasion,lymph node metastasis,metastais and TNM staging of the colon carcinoma.To explore the relationship between Twist gene expression and tumoregenesis,development in colon carcinoma.
Methods:The tumor and cutting edge tissues were gained from 50 cases of colon carcinoma specimens which were collected from surgical resection.Real-time quantitative polymerase chain reaction(real-time PCR) was used to detect the expression of Twist mRNA.Streptavidin biotin complex(SABC ) immunohistochemistry was performed to detect the Twist protein expression.
Results:
1.The expression of Twist mRNA in colon carcinoma tissues is higher than that in cutting edge tissues(P<0.05),Twist gene mRNA transcription in colon carcinoma had statistical significance in different tumor differentiation,invasion depth,lymph node metastasis,metastasis and TNM staging respectively(P<0.05).There were no statistical significance in age and gender and pathological type(P>0.05).
2.The positive rates of Twist protein expression in colon carcinoma and that in cutting edge tissues were 68%and 16%,the Twist protein expression in colon carcinoma tissues is higher than the level in cutting edge tissues(P<0.05).Twist protein expression in colon carcinoma also had statistical significance in different tumor differentiation,invasion depth,lymph node metastasis,metastasis and TNM staging respectively(P<0.05).There were no statistical significance in age and gender and pathological type(P>0.05).
3.The Twist mRNA transcript expression had a positive correlation with protein expression.
Conclusions:
1.The high expression of Twist gene plays an important role in tumoregenesis and development of colon carcinoma.Twist gene acts as one of the characteristics of molecular biology in the process of malignant transformation of colon tumor.
2.The mRNA transcript of Twist gene is positively correlated with its corresponding protein expression in colon carcinoma,indicating that the activation of Twist gene is not only play an important role in the mRNA transcription level,but also in the protein level.
3.The correlations between expression of Twist gene and pathlogical parameters shows that The activation of Twist gene is likely to be an important event in invasion and matastasis of colon carcinoma.
4.The strategy that Twist gene as a gene therapeutic approach will probably become a kind of mean of treatment in colon carcinoma.
方法:收集结肠癌手术切除标本50例,分别切取结肠癌和切端结肠组织;采用实时定量PCR检测50例结肠癌及切端结肠组织Twist基因的mRNA转录水平;运用免疫组织化学(SABC)法检测50例结肠癌及切端结肠组织Twist蛋白的表达水平;结合临床病理资料,进行统计学分析。
结果:
1.结肠癌组织Twist基因mRNA转录水平高于切端结肠组织,差异有统计学意义(P＜0.05),结肠癌组织Twist基因mRNA的转录水平在不同的肿瘤分化程度、浸润深度、淋巴结转移、远处转移及TNM分期之间的差异有统计学意义(P＜0.05),在不同的年龄、性别及病理类型之间差异无统计学意义(P＞0.05)。
2.结肠癌、切端结肠组织中Twist蛋白表达阳性率分别为68%和16%,Twist蛋白在结肠癌组织的表达水平高于切端结肠组织,差异有统计学意义(P＜0.05),结肠癌组织Twist的蛋白表达水平在肿瘤的分化程度、浸润程度、淋巴结转移、远处转移及TNM分期间的差异有统计学意义(P＜0.05),在不同的年龄、性别及病理类型之间差异无统计学意义(P＞0.05)。
3.结肠癌组织Twist的mRNA转录水平与蛋白表达水平存在正相关(P＜0.05)。
结论:
1.Twist基因高表达是结肠癌发生、发展的重要分子事件之一,其参与了结肠癌的恶性转化过程。
2.结肠癌组织Twist mRNA转录水平与蛋白表达水平呈正相关,表明作为转录调控因子的Twist基因的活化是不仅在mRNA的转录水平,而且其最终能翻译成Twist蛋白而发挥其生物学特性。
3.结肠癌组织Twist基因的表达在不同肿瘤的分化程度、浸润深度、淋巴结转移、远处转移及TNM分期之间存在着显著差异,这提示Twist基因在结肠癌侵袭、转移的生物学过程中发挥着一定作用,在一定程度上可作为检测恶性肿瘤进展的生物学指标之一。
4.结肠癌组织Twist基因的高表达提示Twist基因在结肠癌的形成、发展中起重要的促进作用,对Twist基因表达的抑制将可能对肿瘤的生长和转移起到一定的遏制作用,下调Twist的表达可能成为恶性肿瘤基因治疗的一个新的靶点。
Objective:To detect the expression of Twist gene in colon carcinoma tissue and study the association of the changs in tumor differentiation,invasion,lymph node metastasis,metastais and TNM staging of the colon carcinoma.To explore the relationship between Twist gene expression and tumoregenesis,development in colon carcinoma.
Methods:The tumor and cutting edge tissues were gained from 50 cases of colon carcinoma specimens which were collected from surgical resection.Real-time quantitative polymerase chain reaction(real-time PCR) was used to detect the expression of Twist mRNA.Streptavidin biotin complex(SABC ) immunohistochemistry was performed to detect the Twist protein expression.
Results:
1.The expression of Twist mRNA in colon carcinoma tissues is higher than that in cutting edge tissues(P<0.05),Twist gene mRNA transcription in colon carcinoma had statistical significance in different tumor differentiation,invasion depth,lymph node metastasis,metastasis and TNM staging respectively(P<0.05).There were no statistical significance in age and gender and pathological type(P>0.05).
2.The positive rates of Twist protein expression in colon carcinoma and that in cutting edge tissues were 68%and 16%,the Twist protein expression in colon carcinoma tissues is higher than the level in cutting edge tissues(P<0.05).Twist protein expression in colon carcinoma also had statistical significance in different tumor differentiation,invasion depth,lymph node metastasis,metastasis and TNM staging respectively(P<0.05).There were no statistical significance in age and gender and pathological type(P>0.05).
3.The Twist mRNA transcript expression had a positive correlation with protein expression.
Conclusions:
1.The high expression of Twist gene plays an important role in tumoregenesis and development of colon carcinoma.Twist gene acts as one of the characteristics of molecular biology in the process of malignant transformation of colon tumor.
2.The mRNA transcript of Twist gene is positively correlated with its corresponding protein expression in colon carcinoma,indicating that the activation of Twist gene is not only play an important role in the mRNA transcription level,but also in the protein level.
3.The correlations between expression of Twist gene and pathlogical parameters shows that The activation of Twist gene is likely to be an important event in invasion and matastasis of colon carcinoma.
4.The strategy that Twist gene as a gene therapeutic approach will probably become a kind of mean of treatment in colon carcinoma.
引文
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[2]陈孝平.外科学(八年制)[M].北京:人民卫生出版社,2005年:619.
[3]Thisse B,elMessal M,and Perin-Schmitt.The Twist gene:isolation of a Dorso-phila zygotic gene necessary for the establishment of dorsoventarl Pattenr[J].Nucleic Acids Res,1987,15:3439-3453.
[4]Thisse B,C.Stoetzel,C.Gorostiza-Thisse,et al.Sequence of the Twist gene and nuclear localization of its protein in endomesodemral cells of early Drosophila embryos[J].The EMBOJ,1988,7:2175-2183.
[5]Bourez,R.L.,I.M.Mathijssen,J.M.Vaandrager,et al.Apoptotic cell death during normal embryogenesis of the cornal suture:Early detection of apoptosis in mice using annexin V[J].Craniofac.Surg,1997,8:441-445.
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[9]罗庚求,文继舫.Twist的研究进展[J].国际病理科学与临床杂志,2006,26(5)395-397.
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[1]罗庚求,文继舫,Twist的研究进展,[J].国际病理科学与临床杂志.2006,26(5):0395-03
[2]Chen ZF,Behringer RR(1995) Twist is required in head mesenchyme for cranial neural tube morphogenesis.Genes Dev 9:686-699.
[3]Sosic D,Richardson JA,Yu K,et al.(2003) Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity.Cell 112:169-180.
[4]Scaal M,Fuchtbauer EM,Brand-Saberi B(2001) cDermo-1 expression indicates a role in avian skin development.Anat Embryol(Berl) 203:1-7.
[5]Maestro R,Dei Tos AP,Hamamori Y,Krasnokutsky S,Sartorelli V,Kedes L,Doglioni C,Beach DH,Hannon GJ(1999) Twist is a potential oncogene that inhibits apoptosis.Genes Dev 13:2207-2217.
[6]Hornik C,Brand-Saberi B,Rudlof S,et al.Twist is an integrator of SHH,FGF, and BMP signaling[J].Anat Embryol,2004,209(I):31-39.
[7]Grunert S,Jechlinger M,Beug H.Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis[J].Nat Rev Mol Cell Boil,2003,4(8):657-665.
[8]Sosic D,Richardson J A,Yu K,et al.Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity[J].Cell,2003,112(2):169-180.
[9]Stasiopoulos I A,Mironchik Y,Raman A,et al.HOXA5-twist interaction alters p53 h omeostasis in breast cancer cells[J].J Biol Chem,2005,280(3):2294-2299.
[10]Hamamori Y,S artorelli V,Ogrysko V,et al.R egulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A[J].cell,1999,96(3):405-413.
[11]Kwok WK,Ling M T,Lee T W,et al.U p-regulation of TWIST in prostate cancer and its implication as a therapeutic target[J].Cancer Res,2005,65(12):5153-5162.
[12]Rosivatz E,Becker I,Specht K,et al.Differential expression of the epithelial mesenchymal transition regulators snail,SIP1,and twist in gastric[J].Cancer Am J Pathol,2002,161(5):1881-18911
[13]Hoek K,Rimm DL,Williams KR,et al.ExPression Profiling reveals novel Pathways in the transformation of melanocytes to melanomas.Cancer Res,2004,64:5270-82.
[14]Song LB,Liao WT,Mai HQ,et al.The clinical significance of twist expression in nasopharyngeal carcinoma[J].Cancer Lett.2006,242(2):258-65.
[15]Mironchik Y,Winnard P T,Vesuna F,et al.Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer[J].CancerR es,2005,65(23):10801-10809.
[16]关剑,陈孝平,Twist在人干细胞系与正常肝细胞系中的表达差异,[J]腹部外科2007,20(2):115-117.
[17]时昌文,李杰,孙京杰,Twist在胃癌中的表达及其与临床病理学指标关系研究,[J]中国现代普通外科进展,2007,10(3):233-235.
[18]Huber M A,Kraut N,Beug H,et al.Molecular requirements for epithelial-mesenchymal transition during tumor progression[J]..Cu rr Opin Cell Biol,2005,17 (5),548-558.
[19]Yang J,Mani S A,Donaher J L,et al.Twist,a master regulator of morphogenesis,plays an essential role in tumor metastasis[J].Cell,2004,117 (7):927-939.
[20]Jing Yang,Sendurai A,Mani,et al.Twist,a Master Regulator of Morphogenesis,Plays an Essential Role inTumor Metastasis Cell,2004,117:927-939.
[21]Timmerman LA,Grego-Bessa J,Raya A,Bertran E,Perez-Pomares JM,Diez J,et al.Notchpromotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation [J].Genes Dev,2004,18:99-115.
[22]Lu Z,Ghosh S,Wang Z,Hunter T.Downregulation of caveolin-1 function by EGF leading to the loss of E-cadherin,increased transcrptional activity of b catenin,and enhanced tumor cell invasion [J].Cancer Cell,2003,4:499-51
[2]陈孝平.外科学(八年制)[M].北京:人民卫生出版社,2005年:619.
[3]Thisse B,elMessal M,and Perin-Schmitt.The Twist gene:isolation of a Dorso-phila zygotic gene necessary for the establishment of dorsoventarl Pattenr[J].Nucleic Acids Res,1987,15:3439-3453.
[4]Thisse B,C.Stoetzel,C.Gorostiza-Thisse,et al.Sequence of the Twist gene and nuclear localization of its protein in endomesodemral cells of early Drosophila embryos[J].The EMBOJ,1988,7:2175-2183.
[5]Bourez,R.L.,I.M.Mathijssen,J.M.Vaandrager,et al.Apoptotic cell death during normal embryogenesis of the cornal suture:Early detection of apoptosis in mice using annexin V[J].Craniofac.Surg,1997,8:441-445.
[6]Soo,K.,O'Rourke,M.P.,et al.Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo[J].Dev.Biol,2002,247,251-270.
[7]Cai J,Goodman BK,Patel AS,et al.Increased risk for developmental delay inSaethre-Chotzen syndrome associated with TWIST deletions:an improved strategy for TWIST mutation screening[J].Hum Gen,2003,114:68-76.
[8]Ethylin Wang Jabs.A novel mutation in the Twist gene,implicated in Saethre-Chotzen syndrome,is found in the original case of Robinow-Sorauf syndrome[J].Clin.Genet,2003,64:79-82.
[9]罗庚求,文继舫.Twist的研究进展[J].国际病理科学与临床杂志,2006,26(5)395-397.
[10]Sosic D,Richardson JA,Yu K,et al.(2003) Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity.Cell 112:169-180.
[11]Grunert S,Jechlinger M,Beug H.Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis[J].Nat Rev Mol Cell Boil,2003,4(8):657-665.
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