Liu Yong, Cheng Guoping, Qian Jun, Ju HaiXing, Zhu YuPing, Stefano Meucci, Keilholz Ulrich, Li DeChuan
Surgical Department of Colorectal Cancer, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China.
Charité Comprehensive Cancer Center, Berlin, Germany.
Oncotarget. 2017 Jun 13;8(24):38841-38849. doi: 10.18632/oncotarget.16406.
Guanylyl cyclase C (GCC) is a transmembrane surface receptor restricted to intestinal epithelial cells, from the duodenum to the rectum. We compared GCC expression in tumors and normal rectal tissues, and investigated the relation between GCC expression and metastasis and long-term survival of rectal cancer patients. Based on the UICC classification, 42 rectal cancer patients in this study were classified as stage I, 48 patients as stage II, and 90 patients as stage III. Overexpression of GCC was observed in 80 rectal tumors as compared to matched normal tissues, where no strong staining of GCC was observed. An association between GCC mRNA in the circulation and tumor emboli in vessels, CK20 mRNA, distant organ metastasis, and survival status was observed in 100 rectal cancer patients. Univariate Cox regression analysis indicated that tumor emboli in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC mRNA correlated with 5-year disease-free survival (DFS); while lymph node metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall survival (OS). In a multivariate Cox regression model, GCC mRNA level and mesenteric root lymph node metastasis associated with DFS, while GCC mRNA levels associated with OS. Quantification of GCC expression in circulation is a valuable biomarker for assessing tumor burden and predicting outcome in rectal cancer patients.
鸟苷酸环化酶C(GCC)是一种跨膜表面受体,仅存在于从十二指肠到直肠的肠上皮细胞中。我们比较了肿瘤组织和正常直肠组织中GCC的表达情况,并研究了GCC表达与直肠癌患者转移及长期生存之间的关系。根据国际抗癌联盟(UICC)分类,本研究中的42例直肠癌患者被归类为I期,48例为II期,90例为III期。与配对的正常组织相比,在80例直肠肿瘤中观察到GCC过表达,而在正常组织中未观察到GCC的强染色。在100例直肠癌患者中观察到循环中的GCC mRNA与血管中的肿瘤栓子、CK20 mRNA、远处器官转移及生存状态之间存在关联。单因素Cox回归分析表明,血管中的肿瘤栓子、淋巴结转移、肠系膜根部淋巴结转移及GCC mRNA与5年无病生存率(DFS)相关;而淋巴结转移、GCC mRNA及CK20 mRNA与5年总生存率(OS)密切相关。在多因素Cox回归模型中,GCC mRNA水平和肠系膜根部淋巴结转移与DFS相关,而GCC mRNA水平与OS相关。循环中GCC表达的定量分析是评估直肠癌患者肿瘤负荷和预测预后的有价值的生物标志物。