CAJ | 학술논문

目的本课题组前期研究对染色体1q31.1-32.1区域进行杂合缺失精细定位,发现D1S413-D1S2622区域存在高频杂合缺失现象,提示可能有抑癌基因的存在.本研究在此基础上,对该区域与散发性结直肠癌发生相关的抑癌基因开展筛选研究.方法构建包含上述区域基因的基因芯片,对19例散发性结直肠癌标本进行基因芯片扫描,并与其临床病理特征进行统计学分析,筛选该区域与结直肠癌相关的未知抑癌基因,然后对筛选出的候选基因采用Real-time PCR进行初步验证.结果根据前期实验结果,通过检索,挑选了25个基因进行散发性结直肠癌相关基因的筛选.结果发现半胱氨酸甘氨酸富集蛋白1 (cysteine and glycine-rich protein 1,CSRP1)、LMOD1 、PPP1R12B和CFHL3 4个基因表达显著下调.这4个基因表达情况与结直肠癌患者的临床病理特征无关.通过生物信息学分析,推测CSRP1基因可能是该区域中与结直肠癌相关的抑癌基因.通过Real-time PCR验证结果也发现CSRP1基因在结直肠癌组织中表达显著下调,与芯片结果相符.结论 CSRP1基因可能是一个与结直肠癌发生相关的新的抑癌基因.
목적 본과제조전기연구대염색체1q31.1-32.1구역진행잡합결실정세정위,발현D1S413-D1S2622구역존재고빈잡합결실현상,제시가능유억암기인적존재.본연구재차기출상,대해구역여산발성결직장암발생상관적억암기인개전사선연구.방법 구건포함상술구역기인적기인심편,대19례산발성결직장암표본진행기인심편소묘,병여기림상병리특정진행통계학분석,사선해구역여결직장암상관적미지억암기인,연후대사선출적후선기인채용Real-time PCR진행초보험증.결과 근거전기실험결과,통과검색,도선료25개기인진행산발성결직장암상관기인적사선.결과발현반광안산감안산부집단백1 (cysteine and glycine-rich protein 1,CSRP1)、LMOD1 、PPP1R12B화CFHL3 4개기인표체현저하조.저4개기인표체정황여결직장암환자적림상병리특정무관.통과생물신식학분석,추측CSRP1기인가능시해구역중여결직장암상관적억암기인.통과Real-time PCR험증결과야발현CSRP1기인재결직장암조직중표체현저하조,여심편결과상부.결론 CSRP1기인가능시일개여결직장암발생상관적신적억암기인.
Objective In previous study,we carried out refined mapping of loss of heterzygosity (LOH) on 1q31.1-32.1 and found that a minimal region of frequent deletion was located at DIS413-D1S2622,which indicated that the region could harbor a tumor suppressor gene associated with colorectal carcinoma.This study was to screen for the potential tumor suppressor gene (TSG) on D1S413-D1S2622 in Chinese origin patients with sporadic colorectal cancer.Methods 25 genes located in the D1S413-D1S2622 region were chosen and a microarray-based high throughput screening conducted in 19 sporadic colorectal cancers to identify candidate tumor suppressor genes.The relationship between expression levels of candidate genes and the clinicopathological data was analyzed.Real-time PCR was performed to validate the microarray results.Results According to the microarray-based high throughput screening,we found 4 significantly down-expressed genes,including CSRP1,LMOD1,PPP1R12B and CFHL3.There was no significant association between of CFHL3,CSRP1,LMOD1,PPP1R12B expression and the clinicopathological data.CSRP1 could be a colorectal cancer related tumor suppressor gene.CSRP1 was down-regulated in colorectal cancer.Conclusions CSRP1 might be involved in the progression of colorectal cancer.