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High expression of L-type amino acid transporter 1 (LAT1) predicts poor prognosis in pancreatic ductal adenocarcinomas
  1. Nobuyuki Yanagisawa1,2,
  2. Masaaki Ichinoe1,2,
  3. Tetuo Mikami1,2,
  4. Norihiro Nakada1,2,
  5. Kiyomi Hana1,3,
  6. Wasaburo Koizumi4,
  7. Hitoshi Endou3,5,
  8. Isao Okayasu1,2
  1. 1Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
  2. 2Department of Cellular and Histopathology, Kitasato University Graduate School of Medical Science, Kanagawa, Japan
  3. 3J-Pharma Co. Ltd, Shinjyuku, Tokyo, Japan
  4. 4Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
  5. 5Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Nobuyuki Yanagisawa, Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan; czp05616{at}nifty.com

Abstract

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.

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