Establishment of biomarker and prognostic marker of feces and peripheral blood in colorectal cancer patients

结直肠癌发生过程中涉及的基因异常已被阐明。近年来，一些研究者试图通过检测粪便的基因异常来建立高精度的筛查方法。此外，新的结直肠癌患者外周血预后标志物和生物标志物的建立有助于推进结直肠癌的治疗。本研究的目的是利用粪便和外周血检测结直肠癌患者预后的新标志物和生物标志物。我们已经证明DPEP1在正常结肠粘膜中的表达非常低，但在结直肠腺瘤和癌标本中却高表达。DPEP1在结直肠癌中的表达与病理侵袭性及不良预后指标呈负相关。此外，家族性腺瘤性息肉病（FAP）患者p53突变后，DPEP-1也有表达。这些数据表明DPEP1在结肠癌发生的早期阶段表达，并影响癌细胞的侵袭性。虽然我们不能证明粪便在结直肠癌中有显著的基因标记，但我们可以证明sIL-6R的肿瘤表达缺失通过IL-6反式信号通路与结直肠癌疾病进展相关。此外，结直肠癌患者术前外周血分析显示，CXCL16表达升高与疾病进展及预后不良相关。由于该标志物与肝转移密切相关，我们正在继续阐明这些标志物与体内和体外器官特异性转移机制之间的关系。

The gene abnormality that is involved in carcinogenesis of colorectal cancer has been clarified. Recently, some researchers tried to establish the high accurate screening method by detecting the gene abnormalities of the feces. Moreover, the establishment of the new prognostic marker and biomarker of the peripheral blood in colorectal cancer patients can be helped to advance the treatment of colorectal cancer. The aim of this study is to detect the new prognostic marker and biomarker in colorectal cancer patients used with feces and peripheral blood. We have demonstrated that DPEP1 expression in normal colonic mucosa was very low, but it was highly expressed in colorectal adenoma and cancer specimens. DPEP1 expression in colorectal cancer was negatively correlated with parameters of pathological aggressiveness and poor prognosis. In addition, DPEP-1 was expressed after the mutation of p53 in familial adenomatoud polyposis (FAP) patients. These data suggested that DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness. Although we could not demonstrate a significant gene marker of the feces in colorectal cancer, we could showed that loss of tumour expression of sIL-6R was associated with colorectal cancer disease progression via IL-6 trans-signaling pathway. Moreover, analysis of preoperative peripheral blood of colorectal cancer patients showed that increased expression of CXCL16 was associated with disease progression and poor prognosis. Because this marker was strongly correlated with hepatic metastasis, we are being continued to clarify the association between these markers and the mechanism of organ specific metastasis in vivo and in vitro.