单羧酸转运蛋白 1 的表达与胰腺导管腺癌的更好预后和减少淋巴结转移相关。

Expression of Monocarboxylate Transporter 1 Is Associated With Better Prognosis and Reduced Nodal Metastasis in Pancreatic Ductal Adenocarcinoma.

机构信息

From the Division of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa-shi, Chiba.

Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo.

出版信息

Pancreas. 2019 Sep;48(8):1102-1110. doi: 10.1097/MPA.0000000000001369.

DOI:10.1097/MPA.0000000000001369

PMID:31404019

Abstract

OBJECTIVES

Because lactate is believed to support tumor growth, monocarboxylate transporters (MCTs), which transport lactate, have been investigated in multiple tumors. However, the significance of MCTs in pancreatic cancer is unclear.

METHODS

A retrospective survey was conducted on 240 patients who underwent surgical resection for pancreatic ductal adenocarcinoma without preoperative treatment. The expression of MCT1, MCT2, MCT3, MCT4, and the glucose transporter 1 (GLUT1) was assessed in tumor cells and cancer-associated fibroblasts (CAFs) by tissue microarrays and immunohistochemistry. The impact of their expression on patient outcome and clinicopathological characteristics was also analyzed.

RESULTS

In tumor cells, MCT1, MCT2, MCT3, MCT4, and GLUT1 were detected in 52 (22%), 31 (13%), 149 (62%), 204 (85%), and 235 (98%) cases, respectively. In CAFs, MCT2, MCT4, and GLUT1 were detected in 9 (3.8%), 178 (74%), and 36 (15%) cases, respectively. In tumor cells, MCT1 expression was associated with extended overall and progression-free survival and decreased nodal metastasis. Conversely, MCT4 expression in CAFs was associated with shortened survival.

CONCLUSIONS

In tumor cells, MCT1 expression is associated with better prognosis and reduced nodal metastasis in pancreatic cancer, contrary to findings of past in vitro studies. Conversely, MCT4 expression in CAFs is indicative of worse prognosis.

摘要

目的

由于乳酸被认为可以支持肿瘤生长，因此人们对单羧酸转运蛋白（MCT）进行了研究，MCT 可以转运乳酸。然而，MCT 在胰腺癌中的意义尚不清楚。

方法

对 240 例未经术前治疗而行胰导管腺癌手术切除的患者进行回顾性调查。通过组织微阵列和免疫组织化学方法检测肿瘤细胞和癌相关成纤维细胞（CAF）中 MCT1、MCT2、MCT3、MCT4 和葡萄糖转运蛋白 1（GLUT1）的表达。还分析了它们的表达对患者预后和临床病理特征的影响。

结果

在肿瘤细胞中，分别有 52 例（22%）、31 例（13%）、149 例（62%）、204 例（85%）和 235 例（98%）检测到 MCT1、MCT2、MCT3、MCT4 和 GLUT1。在 CAF 中，分别有 9 例（3.8%）、178 例（74%）和 36 例（15%）检测到 MCT2、MCT4 和 GLUT1。在肿瘤细胞中，MCT1 表达与延长的总生存期和无进展生存期以及减少的淋巴结转移有关。相反，CAF 中 MCT4 的表达与生存时间缩短有关。