弥漫大B细胞淋巴瘤是高度异质性肿瘤，尽管R-CHOP方案提高了该肿瘤的总有效率，仍有1/3患者出现原发耐药或缓解后复发而死于肿瘤。原发和获得性耐药是限制疗效的关键因素。多通道多靶点信号传导通路异常、信号网络调控失衡、细胞增殖失控、凋亡受阻，是DLBCL耐药的重要机制。如何以信号通路中的分子靶点作为药物靶标进行耐药逆转实验研究仍有困难。研究表明：NF-KB、PI3K/AKT、PKC、Wnt-/β-catenin等信号通路介导耐药，本组拟选择不同耐药细胞株，用miRNA表达谱芯片筛选信号通路相关耐药microRNA，RT-PCR验证耐药相关miRNA对肿瘤细胞耐药性影响；用蛋白质组学技术分离鉴定化疗敏感性不同DLBCL组织中差异表达的与信号通路相关的蛋白质，对其进行生物信息学分析，进一步进行组织学验证及功能研究，为从mRNA及蛋白水平筛选肿瘤耐药分子标志物及逆转耐药的靶向治疗奠定基础。

Diffuse large B cell lymphoma is a highly heterogeneous tumor, although R - CHOP scheme has improved the total effective rate of the tumor, there are still a third of the patients with primary resistance or eases died of tumor recurrence. Primary or acquired drug resistance is a key factor in limiting effect. Multi-channel and more targets signaling pathways are abnormal, signaling network regulation is out of control, apoptosis, cell proliferation, these are important drug resistance mechanism of DLBCL. How to resistant reversal experiments for molecular targets of drug target in the signal pathway is still difficult. Research shows that: the NF-kappa B, PI3K/AKT, PKC, and Wnt/beta - catenin signaling pathway mediate resistance, we want to screen signaling pathways-associated resistance miRNA using miRNA expression profile chip , and carry out an differential proteomics analysis on the chemosensitivity of DLBCL tissue with high-throughput screening of resistance-associated protein，we will analysis bioinformatics, verify histology and function research for screening the chemotherapy drug resistance related miRNAs and protein from the mRNA and protein level , we are expected to find the miRNA and protein associated with the resistance to chemotherapy and provide new ideas for screening molecular markers of tumor resistance and reversal resistant to targeted therapy．