SARI及CCNl基因在结直肠癌中的表达及其意义

Expression and significance of SARI and CCN1 in human colorectal carcinomas

目的探讨SARI及其下游CCNl基因表达与结直肠癌发生、发展的关系及对预后的影响。方法实时定量PCR检测32例冻存新鲜结直肠癌及癌旁组织SARI、CCNlmRNA表达，逆转录PCR检测人结直肠癌细胞株（Caco一2、HT-29、Lovo）SARI、CCNlmRNA表达。免疫组织化学法检测116例结直肠癌根治切除标本癌及癌旁组织SARI、CCNl蛋白表达。对SARI、CCNl蛋白表达进行关联分析，并分析其与结直肠癌临床病理特征的关系。分析SARI、CCNl蛋白表达水平对患者预后的影响。结果癌组织中SARImRNA表达下调，而CCNlmRNA表达上调（均P〈0．05），在癌细胞株中二者表达趋势与在组织中一致。癌旁组织和癌组织SARI蛋白阳性表达率分别为76．7％和28．4％，CCNl蛋白阳性表达率分别为26．7％和74．1％，差异均有统计学意义（均P〈0．05）；癌组织中SARI蛋白表达与CCNl蛋白表达呈负相关（r=-0．24，P〈0．05）。SARI蛋白阴性表达者肿瘤分化程度差、浸润深度深及TNM分期高（均P〈0．05）；CCNl蛋白阳性表达者，肿瘤浸润深度深且TNM分期高（均P〈0．05）。SARI蛋白阴性表达者，患者术后生存时间明显缩短（x^2=8．47，P〈0．05），SARI蛋白阴性且同时CCNl蛋白阳性表达者，患者术后生存时间进一步缩短（x^2=12．56，P〈0．05）。结论SARI与CCNl异常表达与结直肠癌恶性生物学行为有关，且SARI蛋白阴性表达与结直肠癌患者不良预后有关。

Objective To explore the expressions of SARI （suppressor of AP-1, regulated by IFN） and connective tissue growth factor/cysteine-rich 61/nephroblastoma-I （ CCN1 ） and clarify their influences on the occurrence, development and prognosis of colorectal carcinoma （CRC）. Methods Real-time PCR （polymerase chain reaction） was used to confirm the expressions of SARI and CCN1 at the mRNA level in 32 fresh tissue samples. And the expressions of Caco-2, HT-29 and Lovo were also detected by RT-PCR （reverse transcription-PCR） in cell lines. Tissue specimens were obtained from 116 cases of CRC and the expressions of SARI and CCN1 for each specimen detected by immunohistochemistry. The correlations between the expressions of SARI and CCN1 proteins were summarized. The relationships between the expression levels of SARI and CCN1 and their clinical features in primary CRC were analyzed respectively. The effects of expression levels of SARI and CCN1 proteins on the prognosis were also assessed in 116 CRC cases. Results The expressions of SARI and CCN1 at the mRNA level in fresh cancerous tissues and cell lines decreased and became up-regulated respectively. The positive rate of SARI protein expression was 76. 7% and 28.4% in cancerous and noncancerous tissues respectively （P 〈 0. 05）. The positive rate of CCN1 protein expression was 26. 7% and 74. 1% in cancerous and noncancerous tissues respectively （P 〈 0. 05）. A negative correlation was observed between the expressions of SARI and CCN1 （ r = - 0. 24, P 〈 0. 05）. The negative expression of SARI correlated with a low grade of differentiation, deep infiltration depth and high TNM staging （P 〈 0. 05）. A positive expression of CCN1 correlated with deep infiltration depth and high TNM staging （P 〈 0. 05 ） while a negative expression of SARI correlated with a lower survival rate than that of a positive expression （ x^2 = 8.47, P 〈 0. 05 ） ; additionally, the survival rate of patients with a negative expression of SARI plus a positive expression of CCN1 was further lowered （ x^2 = 12. 56, P 〈 0. 05）. Conclusion The aberrant expressions of SARI and CCN1 correlate with the malignant biobehaviors of CRC. And a negative expression of SARI correlates with a worse prognosis of CRC.