PPP4R1基因与肿瘤相关性的生物信息学预测及在胃癌组织中的初步验证

Bioinformatic prediction of the relationship between PPP4R1 gene with tumor and its preliminary application in gastric cancer

目的:应用生物信息学分析方法预测基因PPP4R1与胃癌发生和转移的关系,并采用RT-PCR进行验证。方法:利用基因功能模块原理,通过IntNetDB找到基因PPP4R1的伙伴基因,应用CFinder工具找其社团基因,Chilibot在线工具分析社团基因与肿瘤的关系,继而推测PPP4R1与胃癌的联系。采用RT-PCR法检测18对分别来自同一患者的转移和原位肿瘤组织、12对分别来自同一患者的原位肿瘤和癌旁正常组织PPP4R1基因表达,对上述生物信息学分析的结果进行验证。结果:生物学分析结果表明,PPP4R1的社团基因有CTDSP2、PPP2R5E、CTDP1、CTDSP1、FLJ22405、MTMR4、PPP1CA、PPP1CB、PPP1CC、PPP2R2A、PPP2R5A、PPP2R5C、PPP3CC,其中与癌相关的基因有9个,与癌及转移相关的基因有2个。PCR验证结果表明:18例原位胃癌组织中有15例基因PPP4R1表达高于其对应的转移组织(P<0.01);12例正常组织有9例高于其对应的癌组织(P<0.01)。结论:基因PPP4R1可能与胃癌的发生和转移相关;生物信息学可能成为研究基因功能快速而有效的新方法。

Objective： To investigate the relationship of PPP4R1 gene with the oncogenesis and metastasis of gastric carcinoma by using bioinformatics analysis, and to verify the result by RT-PCR. Methods： IntNetDB was used to search for the neighborhoods of gene PPP4R1 and cliques by CFinder; Chilibot was used to explore the association between the cliques and carcinoma, then the association of PPP4R1 with gastric carcinoma was deduced. Eighteen pairs of primary and metastatic specimens from the same patient and 12 pairs primary carcinoma and the adjacent normal specimens from the same patient were analyzed by RT-PCR for PPP4R1 expression. Results： It was found that the community genes of PPP4R1 included PPP2R5E, MTMR4, PPP3CC, CTDP1, CTDSP1, FLJ22405, PPP1CB, PPP1CC, PPP2R2A, PPP2R5A, PPP2R5C, CTDSP2, and PPP1CA as searched by Cfinder2. 0 when k = 14. Nine of the genes were associated with carcinoma and 2 associated with carcinoma and metastasis. The result of RT-PCR showed that higher expression of PPP4R1 was found in 15 of the 18 primary gastric cancer specimens compared with the paired metastatic specimens （P^0.01）; higher expression was also found in 9 of the 12 adjacent normal specimens compared with the paired cancer specimens （P〈0.01）. Conclusion： Gene PPP4R1 may be associated with the oncogenesis and metastasis of gastric carcinoma; bioinformatics is an efficient way to investigate function of new genes.