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

结直肠癌患者粪便和外周血生物标志物及预后标志物的建立

基本信息

批准号：
21890106
负责人：
OKUGAWA Yoshinaga
金额：
$ 2.17万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21890106/
关键词：
大腸癌マーカー糞便血液 fecal colonocyte 末梢血 marker carcinogenesis

项目摘要

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.

与结直肠癌发生有关的基因异常已被阐明。最近，一些研究人员试图通过检测粪便基因异常来建立高精度的筛查方法。此外，结直肠癌患者新的预后标志物和外周血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的新预后标志物和生物标志物。我们已经证明DPEP1在正常结肠粘膜中表达非常低，但在结直肠腺瘤和癌症标本中高表达。结直肠癌中DPEP1的表达与病理侵袭性和不良预后参数呈负相关。此外，家族性腺瘤性息肉病（FAP）患者p53突变后也表达DPEP-1。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。尽管我们无法证明结直肠癌粪便中的显着基因标记，但我们可以证明肿瘤 sIL-6R 表达的丧失通过 IL-6 信号转导途径与结直肠癌疾病进展相关。此外，对结直肠癌患者术前外周血的分析表明，CXCL16表达增加与疾病进展和不良预后相关。由于该标志物与肝转移密切相关，因此我们正在继续阐明这些标志物与体内外器官特异性转移机制之间的关联。