Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. To improve its outcome, reliable biomarkers are urgently needed. In this study, we aimed to elucidate the key molecules involved in PDAC progression using proteomics approaches. First, we undertook 2-D electrophoresis to identify the proteins overexpressed in PDAC tissues. Following the analysis of agarose gel spots, cofilin-1 was identified and verified as a candidate protein commonly upregulated in PDAC tissues. In immunohistochemistry, cofilin-1 was strongly expressed in the cytoplasm of PDAC cells. Samples were divided into two groups based on the level of cofilin-1 expression. The high expression group showed significantly higher incidence of hematogenous dissemination in relapsed patients than the low expression group (P = 0.0083). In in vitro experiments, knockdown of cofilin-1 significantly decreased chemotaxis in PDAC cell lines. After we confirmed that cofilin-1 was secreted from PDAC cells, we established a detection system for the immune-complex of cofilin-1 in sera. Using this system, we measured the IC levels of cofilin-1 in sera and observed that the IC levels of cofilin-1 in PDAC patients were higher than those in healthy volunteers and patients with pancreatitis (PDAC vs. healthy volunteers, P < 0.0001; PDAC vs. patients with pancreatitis, P < 0.026). Notably, the IC levels of cofilin-1 showed a stepwise increase during PDAC progression (P = 0.0034), and high IC levels of cofilin-1 indicated poor prognosis of patients after surgery (P = 0.039). These results suggest that the IC of cofilin-1 in sera is a potentially attractive serum biomarker for the prognosis of PDAC.
Division of Clinical Mass Spectrometry, Chiba University Hospital, Chiba, Japan.|Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Mamoru
M
Satoh
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shigetsugu
http://orcid.org/0000-0002-6495-0422
S
Takano
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.|Department of Biochemistry, School of Life and Environmental Science, Azabu University, Kanagawa, Japan.
Kazuyuki
K
Sogawa
R&D Department, Nittobo Medical Co., Ltd., Koriyama, Japan.
Kenta
K
Noda
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hideyuki
H
Yoshitomi
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Masumi
M
Ishibashi
Center for Genomic and Regenerative Medicine, Juntendo University, Tokyo, Japan.
Kaoru
K
Mogushi
Kashiwado Clinic in Port-Square, Kashiwado Memorial Foundation, Chiba, Japan.
Hirotaka
H
Takizawa
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Masayuki
M
Otsuka
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hiroaki
H
Shimizu
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Masaru
M
Miyazaki
Division of Clinical Mass Spectrometry, Chiba University Hospital, Chiba, Japan.|Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Fumio
F
Nomura
D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D051338:Cofilin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference
D000936:Antigen-Antibody Complex; D014408:Biomarkers, Tumor; D051338:Cofilin 1
Cofilin-1; immune-complex; pancreatic cancer; prognosis; serum biomarker