TY - JOUR
T1 - Proteomic analysis of lymphoblastoid cell lines from schizophrenic patients
AU - Yoshimi, Akira
AU - Yamada, Shinnosuke
AU - Kunimoto, Shohko
AU - Aleksic, Branko
AU - Hirakawa, Akihiro
AU - Ohashi, Mitsuki
AU - Matsumoto, Yurie
AU - Hada, Kazuhiro
AU - Itoh, Norimichi
AU - Arioka, Yuko
AU - Kiumura, Hiroki
AU - Kushima, Itaru
AU - Nakamura, Yukako
AU - Shiino, Tomoko
AU - Mori, Daisuke
AU - Tanaka, Satoshi
AU - Hamada, Shuko
AU - Noda, Yukihiro
AU - Nagai, Taku
AU - Yamada, Kiyofumi
AU - Ozaki, Norio
N1 - Funding Information:
We sincerely thank the patients and healthy volunteers for their participation in this study. We would like to express our gratitude to Dr. Ryoko Ishihara, Ms. Hiromi Noma, and Ms. Mami Yoshida for technical assistance and discussion, and Ms. Yukari Mitsui for contributions to creating and managing the database. This study was supported by research grants from the Japan Agency for Medical Research and Development (AMED), the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, the Ministry of Health, Labour and Welfare (MHLW) of Japan, the Japan Society for the Promotion of Science (JSPS), the Japan Science and Technology Agency (JST), Research Group For Schizophrenia, Japan, SENSHIN Medical Research Foundation, Meijo University, the Uehara Memorial Foundation, and GlaxoSmithKline (GSK) Japan; the Grant-in-Aid for “Integrated research on neuropsychiatric disorders” carried out under the Strategic Research Program for Brain Sciences from AMED (JP18dm0107087, JP18dm0207005); the Health and Labour Sciences Research Grants (HLSRG) for Comprehensive Research on Persons with Disabilities from AMED; the Grant-in-Aid for Scientific Research on Innovative Areas, “Glial assembly: a new regulatory machinery of brain function and disorders” from MEXT; the Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from MEXT; the Grant-in-Aid for Young Scientists B (25860999, 17K16403) from JSPS; the Grant-in-Aid for Scientific Research C (16K08421) from JSPS; the Adaptable & Seamless Technology Transfer Program through Target-driven R&D (A-STEP: AS2511400P, AS2621600P) from JST; the Core Research for Evolutional Science and Technology (CREST) from JST; the Academic Frontier Project for Private Universities, Comparative Cognitive Science Institutes, Meijo University; GSK Japan Research Grant 2014.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Although a number of studies have identified several convincing candidate genes or molecules, the pathophysiology of schizophrenia (SCZ) has not been completely elucidated. Therapeutic optimization based on pathophysiology should be performed as early as possible to improve functional outcomes and prognosis; to detect useful biomarkers for SCZ, which reflect pathophysiology and can be utilized for timely diagnosis and effective therapy. To explore biomarkers for SCZ, we employed fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) of lymphoblastoid cell lines (LCLs) (1st sample set: 30 SCZ and 30 CON). Differentially expressed proteins were sequenced by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and identified proteins were confirmed by western blotting (WB) (1st and 2nd sample set: 60 SCZ and 60 CON). Multivariate logistic regression analysis was performed to identify an optimal combination of biomarkers to create a prediction model for SCZ. Twenty protein spots were differentially expressed between SCZ and CON in 2D-DIGE analysis and 22 unique proteins were identified by LC-MS/MS. Differential expression of eight of 22 proteins was confirmed by WB. Among the eight candidate proteins (HSPA4L, MX1, GLRX3, UROD, MAPRE1, TBCB, IGHM, and GART), we successfully constructed logistic regression models comprised of 4- and 6-markers with good discriminative ability between SCZ and CON. In both WB and gene expression analysis of LCL, MX1 showed reproducibly significant associations. Moreover, Mx1 and its related proinflamatory genes (Mx2, Il1b, and Tnf) were also up-regulated in poly I:C-treated mice. Differentially expressed proteins might be associated with molecular pathophysiology of SCZ, including dysregulation of immunological reactions and potentially provide diagnostic and prognostic biomarkers.
AB - Although a number of studies have identified several convincing candidate genes or molecules, the pathophysiology of schizophrenia (SCZ) has not been completely elucidated. Therapeutic optimization based on pathophysiology should be performed as early as possible to improve functional outcomes and prognosis; to detect useful biomarkers for SCZ, which reflect pathophysiology and can be utilized for timely diagnosis and effective therapy. To explore biomarkers for SCZ, we employed fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) of lymphoblastoid cell lines (LCLs) (1st sample set: 30 SCZ and 30 CON). Differentially expressed proteins were sequenced by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and identified proteins were confirmed by western blotting (WB) (1st and 2nd sample set: 60 SCZ and 60 CON). Multivariate logistic regression analysis was performed to identify an optimal combination of biomarkers to create a prediction model for SCZ. Twenty protein spots were differentially expressed between SCZ and CON in 2D-DIGE analysis and 22 unique proteins were identified by LC-MS/MS. Differential expression of eight of 22 proteins was confirmed by WB. Among the eight candidate proteins (HSPA4L, MX1, GLRX3, UROD, MAPRE1, TBCB, IGHM, and GART), we successfully constructed logistic regression models comprised of 4- and 6-markers with good discriminative ability between SCZ and CON. In both WB and gene expression analysis of LCL, MX1 showed reproducibly significant associations. Moreover, Mx1 and its related proinflamatory genes (Mx2, Il1b, and Tnf) were also up-regulated in poly I:C-treated mice. Differentially expressed proteins might be associated with molecular pathophysiology of SCZ, including dysregulation of immunological reactions and potentially provide diagnostic and prognostic biomarkers.
UR - http://www.scopus.com/inward/record.url?scp=85065114322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065114322&partnerID=8YFLogxK
U2 - 10.1038/s41398-019-0461-2
DO - 10.1038/s41398-019-0461-2
M3 - Article
C2 - 31011151
AN - SCOPUS:85065114322
VL - 9
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 126
ER -