L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer
L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer
复制标题
DOI：
10.1111/j.1440-1827.2008.02319.x
复制
发表时间：
2009-01-01
影响因子：
2.2
通讯作者：
Okayasu, Isao
中科院分区：
文献类型：
--
作者：
Sakata, Takeshi;Ferdous, Golam;Okayasu, Isao
为了寻找可靠的高级别恶性肿瘤的生物标志物，研究了活检样本中免疫组织化学l型氨基酸转运蛋白1 （LAT1）的表达与前列腺癌患者预后的关系，并用新开发的抗人LAT1单克隆抗体检测。采用改进的Sinicrope等方法评估首次活检样本的免疫组织化学LAT1表达强度和评分，发现研究组114例手术治疗患者整体生存率较差（P分别为0.0002和0.0270）。病理T3 + T4组LAT1强度与预后有显著相关（P = 0.0057）。多因素分析表明，与Gleason评分和Ki-67标记指数相比，LAT1强度和评分是更可靠的预后指标。63例不能手术的肿瘤患者的LAT1强度和评分与预后也存在相关性（P分别为0.0070和< 0.0001）。临床T3 + T4组预后差异亦有统计学意义（P分别为0.0091和0.0244）。此外，LAT1表达与Gleason评分的结合与预后有更可靠的相关性。因此，前列腺癌中LAT1表达升高是一种新的独立的高级别恶性肿瘤生物标志物，可与主要依赖于细胞和结构非典型性的Gleason评分一起用于评估预后。
To find reliable biomarkers for high-grade malignancy, the relationship between immunohistochemical L-type amino-acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki-67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and < 0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis.