Nakazawa Toshiyuki, Goi Takanori, Hirono Yasuo, Yamaguchi Akio
First Department of Surgery, University of Fukui, Fukui, Japan.
Ann Surg Oncol. 2015 May;22(5):1496-503. doi: 10.1245/s10434-014-4150-3. Epub 2014 Oct 21.
Hematogenous metastasis, regarded as closely related to angiogenic growth factors, is associated with colorectal cancer prognosis. The angiogenic growth factor prokineticin 1 (PROK1) has been cloned from endocrine cells. However, its protein expression in human malignant tumors has not been studied. The current study established the anti-PROK1 monoclonal antibody (mAb) and examined the relationship between the expression of PROK1 protein and human colorectal cancer.
The expression of PROK1 protein was assessed in 620 resected sporadic colorectal cancer tissue samples by immunohistochemical staining with in-house-developed human PROK1 mAb to investigate the relationship of PROK1 expression to clinicopathologic factors, recurrence, and survival rate and to evaluate its prognostic significance.
The expression of PROK1 protein was detected in 36 % (223/620) of human primary colorectal cancer lesions but no in the healthy mucosa adjacent to the colorectal cancer lesions. According to the clinicopathologic examinations, the frequency of positive PROK1 expression was significantly higher in cases with serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, liver metastasis, hematogenous metastasis, and higher stage disease. The recurrence rate and prognosis for patients with PROK1 expression-positive lesions were significantly worse. In the Cox proportional hazard model, PROK1 expression was an independent prognostic factor.
The expression of PROK1 protein was identified for the first time as a new prognostic factor in colorectal cancer.
血行转移与血管生成生长因子密切相关,与结直肠癌预后相关。血管生成生长因子促动力蛋白1(PROK1)已从内分泌细胞中克隆出来。然而,其在人类恶性肿瘤中的蛋白表达尚未得到研究。本研究制备了抗PROK1单克隆抗体(mAb),并检测了PROK1蛋白表达与人类结直肠癌之间的关系。
采用自行研制的人PROK1 mAb进行免疫组织化学染色,评估620例手术切除的散发性结直肠癌组织样本中PROK1蛋白的表达,以研究PROK1表达与临床病理因素、复发及生存率的关系,并评估其预后意义。
在36%(223/620)的人类原发性结直肠癌病变中检测到PROK1蛋白表达,但在结直肠癌病变旁的健康黏膜中未检测到。根据临床病理检查,在有浆膜侵犯、淋巴侵犯、静脉侵犯、淋巴结转移、肝转移、血行转移及更高分期疾病的病例中,PROK1表达阳性的频率显著更高。PROK1表达阳性病变患者的复发率和预后明显更差。在Cox比例风险模型中,PROK1表达是一个独立的预后因素。
首次确定PROK1蛋白表达为结直肠癌的一个新的预后因素。