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.
- Pancreatic Cancer
- KI 67
- Cancer Research
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Contributors NY participated in the study design, evaluated immunoreactivity, performed statistical analyses, and wrote the manuscript. MI, TM and NN advised about the evaluation of immunoreactivity. KH performed laboratory work. WK provided the clinical information. HE supplied the antibody for immunohistochemistry. IO supervised the study design and evaluated immunoreactivity.
Funding This study was partly supported by a Grant-in-Aid from the New Energy and Industrial Technology Development Organization, Ministry of Economy, Trade and Industry, Japan.
Ethics approval Tissue samples were used with written informed consent of the patients. The study was approved by the Kitasato University School of Medicine and Kitasato University Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.