Proteomic analysis targeting stroma of pancreatic cancer

胰腺癌是一种侵袭性的恶性肿瘤。近年来研究发现，肿瘤间质与肿瘤细胞的增殖、凋亡、分化和侵袭密切相关。在本项目中，我们全面检测了胰腺肿瘤或正常胰腺间质中表达的蛋白质，发现CRMP4在胰腺肿瘤间质中与正常胰腺组织相比差异表达。在所有CRMPs中，只有crmp 4在胰腺癌组织中差异表达。CRMP4阳性表达与低分化及肝转移密切相关。多因素分析提示静脉侵犯和CRMP4过表达是影响生存的预后因素。使用siRNA敲低CRMP4降低细胞侵袭，但不影响增殖。我们的研究结果表明，CRMP4通过增加胰腺癌细胞的侵袭性与预后不良显著相关，并且可以成为胰腺癌的新的治疗靶点。

Pancreatic cancer has an aggressive malignancy. Recently, stroma in tumor is reported to be associated with cancer-cell proliferation, apoptosis, differentiation and invasion in several cancers. In this project, we comprehensively examined proteins expressing in the stroma of pancreatic tumors or of normal pancreas, and found that CRMP4 differentially expressed in pancreatic tumor stroma compared to normal pancreatic tissue. Of all the CRMPs, only crmp4 was differentially expressed in pancreatic cancer tissues. CRMP4 staining was highly correlated with poor differentiation and liver metastasis. Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival. CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. Our results suggested that CRMP4 is significantly associated with poor prognosis by increasing pancreatic cancer cell invasiveness, and can be a novel therapeutic target for pancreatic cancer.