生物芯片与疾病标志物

§1.肿瘤诊断与预后

肿瘤的发生和发展是一个长期、渐进的过程,涉及细胞生命活动的多个方面,如生长、分化、凋亡、运动等。我们利用不同的生物芯片平台,如mRNA表达谱芯片、microRNA表达谱芯片、SNP分型芯片、转录因子芯片、细胞芯片和组织芯片等,全面系统地研究了肿瘤的发病机制,对肿瘤进行诊断、分子分型和个体化用药。

图1 利用miRNA表达差异区分    图片8

     图1 利用miRNA表达差异区分食管癌与癌旁组织    图2 利用miR-103/107对食管癌病人的预后进行分析

    图片9     图片10

     图3 利用基因表达谱可以准确区分肝癌、癌旁      图4 利用miRNA表达差异区分肝癌、肝脏良性病变

                和正常肝组织                    和健康对照

图5 疾病预测DNA芯片

图5 疾病预测DNA芯片

代表论文

  1. Qin, W., Dong, P., Ma, C., Mitchelson, K., Deng, T., Zhang, L., Sun, Y., Feng, X., Ding, Y., Lu, X., He, J., Wen, H. and Cheng, J. (2011) "MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways" Oncogene, 2011(12):1-9.
  2. Tan, X., Zhang, L., Qin, W., Hang, J., Chen, Z., Li, B., Zhang, C., Wan, J., Zhou, F., Shao, K., Sun, Y., Wu, J., Qiu, B., Li, N., Shi, S., Feng, X., Zhao, S., Wang, Z., Zhao, X., Yu, Z., Mitchelson, K., Cheng, J., Guo, Y. and He, J. (2011) "A 5-MicroRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis" Clinical Cancer Research, 17(21):6802-6811.
  3. Guo, H., Liu, H., Mitchelson, K., Rao, H., Luo, M., Xie, L., Sun, Y., Zhang, L., Lu, Ying., Liu, R., Ren, A., Liu, S., Zhou, S., Zhu, J., Zhou, Y., Huang, A., Wei, L., Guo, Y. and Cheng, J. (2011) "MicroRNAs-372/373 promote the expression of hepatitis B virus through the targeting of nuclear factor I/B" Hepatology, 54(3):808–819.
  4. Yu, J., Zhang, L., Chen, A., Xiang, G., Wang, Y., Wu, J., Mitchelson, K., Cheng, J. and Zhou, Y. (2008) “Identification of the gene transcription and apoptosis mediated by TGF-beta-Smad2/3-Smad4 signaling” Journal of Cellular Physiology, 215(2):422-433.
  5. Guo,Y.,Chen, Z., Zhang, L., Zhou, F., Shi, S., Feng, X., Li, B., Meng, X., Ma, X., Luo, M., Shao, K., Li, N., Qiu, B., Mitchelson, K., Cheng, J. and He, J. (2008) “Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma” Cancer Research, 68(1):26-33.
  6. Li, W., Xie, L., He, X., Li, J., Tu, K., Wei, L., Wu, J., Guo, Y., Ma, X., Zhang, P., Pan, Z., Hu, X., Zhao, Y., Xie, H., Jiang, G., Chen, T., Wang, J., Zheng, S., Cheng, J., Wan, D., Yang, S., Li, Y. and Gu, J. (2008) “Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma” International Journal of Cancer, 123:1616-1622.

§2.重大疾病关联分析研究

我们利用基因芯片对重大疾病作了全基因组关联分析,可以帮助寻找与患病风险关联的遗传因子,为预测医疗、预防医疗和个体化诊疗打下了基础。

图6 GWAS Manhattan 分析图

图6 GWAS Manhattan 分析图

图7 唇腭裂部分SNP关联位点

图7 唇腭裂部分SNP关联位点

代表论文

  1. Sun, Y., Huang, Y., Yin, A., Pan, Y., Wang, Y., Wang, C., Du, Y., Wang, M., Lan, F., Hu, Z., Wang, G., Jiang, M., Ma, J., Zhang, X., Ma, H., Ma, J., Zhang, W., Huang, Q., Zhou, Z., Ma, L., Li, Y., Jiang, H., Xie, L., Jiang, Y., Shi, B., Cheng, J., Shen, H., Wang, L. and Yang, Y. (2015) “Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate” Nature Communications, 6:6414.
  2. Yang, T., Chen, X., Guo, Y., Lei, S., Wang, J., Zhou, Q., Pan, F., Chen, Y., Zhang, Z., Dong, S., Xu, X., Yan, H., Liu, X., Qiu, C., Zhu, X., Chen, T., Li, M., Zhang, H., Zhang, L., Drees, B., Hamilton, J., Papasian, C., Recker, R., Song, X., Cheng, J. and Deng, H. (2008) “Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis” The American Journal of Human Genetics, 83(6):663-674.