散发性结直肠癌相关半胱氨酸甘氨酸富集蛋白1抑癌基因的筛选

A screening study for a novel tumor suppressor gene CSRP1 in Chinese origin patients with sporadiccolorectal cancer

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-D1$2622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-timePCR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 protein1，CSRPl）、LMODl、PPPlR12B和CFHL34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CSRPl基因可能是该区域中与结直肠癌相关的抑癌基因。通过Real-timePCR验证结果也发现CSRPl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CSRPl基因可能是一个与结直肠癌发生相关的新的抑癌基因。

Objective In previous study, we carried out refined mapping of loss of heterzygosity （LOH） on lq31. 1-32. 1 and found that a minimal region of frequent deletion was located at D1S413D1S2622, 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 D1 $413-D1 $2622 in Chinese origin patients with sporadic colorectal cancer. Methods 25 genes located in the D1S413- D1S2622 region were chosen and a mieroarray-based high throughput screening conducted in 19 sporadic eolorectal cancers to identify candidate tumor suppressor genes. The relationship between expression levels of candidate genes and the clinieopathological data was analyzed. Real-time PCR was performed to validate the mieroarray 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 clinicopathologieal data. CSRP1 could be a coloreetal cancer related tumor suppressor gene. CSRP1 was down-regulated in eoloreetal cancer. Conclusions CSRP1 might be involved in the progression of eolorectal cancer.