Open AccessStromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma
Author(s) -
Yoshihisa Suzuki,
Tatsuyuki Takadate,
Masamichi Mizuma,
Hiroki Shima,
Takashi Suzuki,
Tomoyoshi Tachibana,
Muneaki Shimura,
Tatsuo Hata,
Masahiro Iseki,
Koji Kawaguchi,
Takeshi Aoki,
Hiroki Hayashi,
Takanori Morikawa,
Kazuhiko Nakagawa,
Fuyuhiko Motoi,
Takeshi Naitoh,
Kazuhiko Igarashi,
Michiaki Unno
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0235904
Subject(s) - hemopexin , pancreatic cancer , medicine , metastasis , adenocarcinoma , pathology , lymph node , stroma , stromal cell , cancer research , immunohistochemistry , oncology , cancer , biology , heme , biochemistry , enzyme
Pancreatic ductal adenocarcinoma is one of the most aggressive types of cancer. Certain proteins in the tumor microenvironment have attracted considerable attention owing to their association with tumor invasion and metastasis. Here, we used proteomics to identify proteins associated with lymph-node metastasis, which is one of the prognostic factors. We selected lymph node metastasis-positive and -negative patients (n = 5 each) who underwent pancreatectomy between 2005 and 2015 and subjected to comprehensive proteomic profiling of tumor stroma. A total of 490 proteins were detected by mass spectrometry. Software analysis revealed that nine of these proteins were differentially expressed between the two patient groups. We focused on hemopexin and ferritin light chain based on immunohistochemistry results. We assessed the clinicopathological data of 163 patients and found that hemopexin expression was associated with UICC N2 ( p = 0.0399), lymph node ratio ( p = 0.0252), venous invasion ( p = 0.0096), and lymphatic invasion ( p = 0.0232). Notably, in vitro assays showed that hemopexin promotes invasion of the pancreatic cancer cells. Our findings suggest that hemopexin is a lymph node metastasis-associated protein that could potentially serve as a useful therapeutic target or biomarker of pancreatic ductal adenocarcinoma.