Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays.
In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues. Insulin-like growth factor-binding protein 7 (IGFBP7), S100 calcium binding protein A9 (S100A9), interleukin-10 (IL-10) and mucin 6 (MUC6) exhibited the most profound variations. For an evaluation of the proteins' capacity for discriminating gastric cancer, a Receiver Operating Characteristic curve analysis was performed, yielding an accuracy (area under the curve) value of 89.2% for distinguishing tumor from non-tumorous tissue. For confirmation, immunohistological analyses were done on tissue slices prepared from another cohort of patients with gastric cancer. The utility of the 17 marker proteins, and particularly the four molecules with the highest specificity for gastric adenocarcinoma, is discussed for them to act as candidates for diagnosis, even in serum, and targets for therapeutic approaches.
Division of Biostatistics, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. m.sill@dkfz.de.
Martin
M
Sill
Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. schroeder@sciomics.de.|Sciomics GmbH, In Neuenheimer Feld 583, 69120 Heidelberg, Germany. schroeder@sciomics.de.
Christoph
C
Schröder
Department of General, Visceral and Transplantation Surgery, University Clinic Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. shenying_0624@outlook.com.
Ying
Y
Shen
Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. a.marzoq@dkfz.de.
Aseel
A
Marzoq
Medical Faculty, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia. komel@mf.uni-lj.si.
Radovan
R
Komel
Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. j.hoheisel@dkfz.de.
Jörg D
JD
Hoheisel
Department of General, Visceral and Transplantation Surgery, University Clinic Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Henrik.Nienhueser@med.uni-heidelberg.de.
Henrik
H
Nienhüser
Department of General, Visceral and Transplantation Surgery, University Clinic Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Thomas1.schmidt@med.uni-Heidelberg.de.
Thomas
T
Schmidt
Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. kastelic.dkfz@gmail.com.
Damjana
D
Kastelic
adenocarcinoma; affinity based proteomics; antibody microarrays; biomarker identification; gastric cancer