背景:1型大氨基酸转运蛋白(LAT1)为癌细胞提供了蛋白质合成和细胞生长所必需的氨基酸,并可以预测患者的预后。此外,LAT1抑制可以是治疗靶标。本研究旨在探讨LAT1表达在肺癌中的预后意义。特别注意腺癌亚型。
方法:使用从1995年至2008年在我院手术切除的肺癌标本中获得的1,560个总核心的组织微阵列(TMA)。总的来说,发现795例腺癌,717人接受了进一步评估.评估整个载玻片和TMA核心的免疫组织化学染色以设定H评分截止值。.根据腺癌的亚型检查LAT1的免疫组织化学表达。统计分析探讨了LAT1的预后意义。
结果:腺癌占所有病例的71.8%(n=795),216例(27.1%)表达LAT1。795例病例分为5种亚型:麻药(n=29,3.6%),乳头状(n=601,75.6%),腺泡(n=58,7.3%),和固体(n=9,1.1%);795例中的717例根据排除标准进行了进一步评估。LAT1正比率随着建筑等级的增加而增加。值得注意的是,在乳头状腺癌中,与阴性组相比,LAT1阳性组的总生存率显着降低(10年生存率:45.6%vs.60.8%,p<0.001)。
结论:肺腺癌高级别亚型中LAT1表达较高。此外,LAT1表达对预测预后有用,特别是乳头状腺癌,促进乳头状腺癌的预后分层。
BACKGROUND: Large amino acid transporter type 1 (LAT1) provides cancer cells with essential amino acids for both protein synthesis and cell growth and may predict patient prognosis. Additionally, LAT1 inhibition can be a therapeutic target. This study aimed to examine the prognostic significance of LAT1 expression in lung cancer, paying special attention to adenocarcinoma subtypes.
METHODS: Tissue microarrays (TMA) of 1,560 total cores obtained from surgically resected lung cancer specimens between 1995 and 2008 at our hospital were used. Overall, 795 cases of adenocarcinoma were identified, and 717 underwent further evaluation. Immunohistochemical staining of whole slides and TMA cores were assessed to set H-score cutoff value.. Immunohistochemical expression of LAT1 was examined based on the subtypes of adenocarcinoma. Statistical analyses explored the prognostic significance of LAT1.
RESULTS: Adenocarcinoma accounted for 71.8% of all cases (n = 795), and 216 cases (27.1%) expressed LAT1. The 795 cases were categorized into five subtypes: lepidic (n = 29, 3.6%), papillary (n = 601, 75.6%), acinar (n = 58, 7.3%), and solid (n = 9, 1.1%); 717 of the 795 cases were further assessed according to the exclusion criteria. The LAT1-positive ratio increased as the architectural grade increased. Notably, in papillary adenocarcinoma, the LAT1-positive group had significantly lower overall survival compared to the negative group (10-year survival: 45.6% vs. 60.8%, p < 0.001).
CONCLUSIONS: LAT1 expression was higher in high-grade subtypes of pulmonary adenocarcinoma. Moreover, LAT1 expression is useful for predicting prognosis, particularly in papillary adenocarcinoma, facilitating prognostic stratification of papillary adenocarcinoma.