Gu C, Oyama T, Osaki T, Li J, Takenoyama M, Izumi H, Sugio K, Kohno K, Yasumoto K
Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Br J Cancer. 2004 Jan 26;90(2):436-42. doi: 10.1038/sj.bjc.6601531.
Initial glycosylation of mucin-type O-linked protein is catalysed by one of the UDP-GalNAc: polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3). O-glycosylation is important in the binding of cell adhesion molecules, cell differentiation, invasion, and metastasis in tumours. This study was designed to detect GalNAc-T3 expression in lung adenocarcinoma by using immunohistochemical staining, and to evaluate the relationship between the GalNAc-T3 expression level and prognosis and recurrence in completely resected lung adenocarcinoma patients. A low expression of GalNAc-T3 was detected in the cytoplasm of tumour cells in 79 of 148 patients (53.4%) with lung adenocarcinoma. The low expression of GalNAc-T3 was associated with poorly differentiated tumour (P<0.0001), poor pathologic stage (P<0.0001), lymph node metastasis (P<0.0001), and tumour recurrence (P=0.016). The lung carcinoma patients with low GalNAc-T3 expression had a poorer prognosis than those with high GalNAc-T3 expression, using both univariate and multivariate analyses (overall survival: P<0.0001 and P=0.011, respectively). In addition, multivariate analysis of the clinicopathological characteristics of stage I lung adenocarcinoma indicated that the low expression of GalNAc-T3 was a significant independent factor for predicting poor prognosis and early recurrence (P=0.006, rr=2.87 and P=0.019, rr=3.05, respectively). The low expression of GalNAc-T3 may be a useful marker for predicting poor prognosis and early recurrence in completely resected lung carcinoma patients, particularly patients with stage I diseases.
粘蛋白型O-连接蛋白的初始糖基化由UDP-N-乙酰半乳糖胺:多肽N-乙酰半乳糖胺基转移酶-3(GalNAc-T3)之一催化。O-糖基化在细胞粘附分子的结合、细胞分化、肿瘤侵袭和转移中起重要作用。本研究旨在通过免疫组织化学染色检测GalNAc-T3在肺腺癌中的表达,并评估GalNAc-T3表达水平与完全切除的肺腺癌患者预后及复发之间的关系。148例肺腺癌患者中有79例(53.4%)肿瘤细胞胞质中检测到GalNAc-T3低表达。GalNAc-T3低表达与肿瘤低分化(P<0.0001)、病理分期差(P<0.0001)、淋巴结转移(P<0.0001)及肿瘤复发(P=0.016)相关。单因素和多因素分析均显示,GalNAc-T3表达低的肺癌患者预后比GalNAc-T3表达高的患者差(总生存期:分别为P<0.0001和P=0.011)。此外,对Ⅰ期肺腺癌临床病理特征的多因素分析表明,GalNAc-T3低表达是预测预后不良和早期复发的重要独立因素(分别为P=0.006,相对风险=2.87和P=0.019,相对风险=3.05)。GalNAc-T3低表达可能是预测完全切除的肺癌患者,尤其是Ⅰ期疾病患者预后不良和早期复发的有用标志物。