TY - JOUR
T1 - Stromal expression of hemopexin is associated with lymph-node metastasis in pancreatic ductal adenocarcinoma
AU - Suzuki, Yukie
AU - Takadate, Tatsuyuki
AU - Mizuma, Masamichi
AU - Shima, Hiroki
AU - Suzuki, Takashi
AU - Tachibana, Tomoyoshi
AU - Shimura, Mitsuhiro
AU - Hata, Tatsuo
AU - Iseki, Masahiro
AU - Kawaguchi, Kei
AU - Aoki, Takeshi
AU - Hayashi, Hiroki
AU - Morikawa, Takanori
AU - Nakagawa, Kei
AU - Motoi, Fuyuhiko
AU - Naitoh, Takeshi
AU - Igarashi, Kazuhiko
AU - Unno, Michiaki
N1 - Publisher Copyright:
© 2020 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088051307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088051307&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0235904
DO - 10.1371/journal.pone.0235904
M3 - Article
C2 - 32663208
AN - SCOPUS:85088051307
SN - 1932-6203
VL - 15
JO - PLoS One
JF - PLoS One
IS - 7
M1 - e0235904
ER -
