High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas
High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas
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DOI：
10.1136/jclinpath-2012-200826
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发表时间：
2012-11-01
影响因子：
3.4
通讯作者：
Okayasu, Isao
中科院分区：
文献类型：
--
作者：
Yanagisawa, Nobuyuki;Ichinoe, Masaaki;Okayasu, Isao
背景与目的针对L型氨基酸转运蛋白1（LAT 1）的分子靶向治疗是目前唯一的靶向治疗方法，具有广阔的发展前景。LAT 1表达在胰腺癌中作为预后预测因子进行了研究。方法采用免疫组化方法对66例手术切除的胰腺导管腺癌（PDAC，n = 66）进行研究。作为参考，导管内乳头状粘液癌（IPMC，包括导管内乳头状粘液瘤（IPMN）与高度异型增生或与相关的浸润性癌，n = 13）和腺瘤（IPMA，包括IPMN与低，中级异型增生，n = 5）也进行了检查。Kaplan-Meier分析显示LAT 1-高和-低评分在PDAC中存在显著差异。即使在每个Ki-67标记指数（LI）低和高PDAC组（截断值40%）中，LAT 1高表达也可预测不良预后。多因素分析显示LAT 1表达、Ki-67 LI、肿瘤分化程度和肿瘤大小是影响PDAC患者预后的独立因素。结论LAT 1在PDAC中的异常过表达与Ki-67 LI无关，提示PDAC患者预后不良，LAT 1抑制剂可作为今后抗肿瘤治疗的潜在靶点。
Background and aims Molecular target therapy against L-type amino acid transporter 1 (LAT1) is unique and expected to be developed soon. LAT1 expression was investigated in pancreatic cancer as a prognostic predictor.Methods Surgically resected pancreatic ductal adenocarcinomas (PDAC, n = 66) were investigated using immunohistochemistry. For reference, intraductal papillary mucinous carcinomas (IPMC, including intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia or with an associated invasive carcinoma, n = 13) and adenomas (IPMA, including IPMN with low- and intermediate-grade dysplasia, n = 5) were also examined.Results LAT1 expression scores increased from PDAC to IPMA to IPMC. Kaplan-Meier analysis showed significant differences between LAT1-high and -low scores in PDAC. Even in each Ki-67-labelling index (LI) low and high PDAC group (cut off 40%), high LAT1 expression could also predict poor prognosis. Multivariable analysis showed that LAT1 expression, Ki-67 LI, tumour differentiation and size were individual prognostic factors.Conclusions LAT1 aberrant overexpression in PDAC predicts poor prognosis, independent of Ki-67 LI, and offers a potential target for future anticancer therapy with its inhibitors.