Kocer Belma, McKolanis John, Soran Atilla
Department of Immunology, University of Pittsburg School of Medicine, Pittsburgh, PA, USA.
BMC Gastroenterol. 2006 Jan 12;6:4. doi: 10.1186/1471-230X-6-4.
MUC5AC is a secreted mucin aberrantly expressed by colorectal polyps and carcinoma. It has been hypothesized that aberrant expression of MUC5AC in colorectal carcinoma tissues increased the overall survival of patients with colorectal carcinoma. The present study investigates the incidence of naturally occurring MUC5AC antibodies in the sera of normal individuals, patients with colonic polyps and patients with advanced colorectal carcinoma. A second aim was to determine the relationship of MUC5AC antibody with the prognosis of colorectal carcinoma.
Free circulating MUC5AC antibodies were measured using an enzyme-linked immunosorbent assay with a synthetic peptide corresponding to an 8 aa. segment of MUC5AC tandem repeat region. Immunohistochemical analysis was completed to demonstrate MUC5AC expression in the polyp specimens.
MUC5AC antibodies were detected in 6 of 22 (27.3%) healthy subjects, 9 of 20 (45%) polyp patients, 18 of 30 (60%) patients with colorectal cancer. The presence of circulating free MUC5AC antibody levels was significantly correlated with expression of MUC5AC in polyp sections. Serum MUC5AC antibody positivity was higher in patients with colon located tumors, advanced stage and poorly differentiated tumors were found negatively affecting patient survival in our study. MUC5AC antibody positivity was higher in patients with poor prognostic parameters. Disease free survival and overall survival were shorter in this group of patients. In the multivariate analysis MUC5AC antibody positivity didn't find an independent prognostic factor on prognosis.
Decreased survival in colorectal carcinoma patients with MUC5AC antibody positivity may be due to a decrease in the MUC5AC expression in tumor tissues of surviving carcinoma patients.
MUC5AC是一种由结肠息肉和癌异常表达的分泌性黏蛋白。据推测,MUC5AC在结直肠癌组织中的异常表达可提高结直肠癌患者的总生存率。本研究调查正常个体、结肠息肉患者和晚期结直肠癌患者血清中天然存在的MUC5AC抗体的发生率。第二个目的是确定MUC5AC抗体与结直肠癌预后的关系。
使用酶联免疫吸附测定法,采用与MUC5AC串联重复区域的8个氨基酸片段相对应的合成肽,检测游离循环MUC5AC抗体。完成免疫组织化学分析以证明息肉标本中MUC5AC的表达。
在22名健康受试者中的6名(27.3%)、20名息肉患者中的9名(45%)、30名结直肠癌患者中的18名(60%)检测到MUC5AC抗体。循环游离MUC5AC抗体水平的存在与息肉切片中MUC5AC的表达显著相关。在我们的研究中,结肠部位肿瘤、晚期和低分化肿瘤患者的血清MUC5AC抗体阳性率较高,且发现这些因素对患者生存有负面影响。预后参数较差的患者MUC5AC抗体阳性率较高。该组患者的无病生存期和总生存期较短。在多变量分析中,MUC5AC抗体阳性在预后方面未发现是独立的预后因素。
MUC5AC抗体阳性的结直肠癌患者生存率降低可能是由于存活癌患者肿瘤组织中MUC5AC表达降低所致。