Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study.
BACKGROUND
The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers.


METHODS
The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively.


RESULTS
Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p = 0.044). Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL) versus controls (1.04 ± 0.03 ng/mL) (p < 0.01), with an area under the ROC curve (AUC) being 0.858 comparable to that of CEA (0.867).


CONCLUSIONS
BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan ; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Sum-Fu
SF
Chiang
Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Chih-Yen
CY
Kan
Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
Yung-Chin
YC
Hsiao
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan ; Chang Gung University College of Medicine, Linkou, Taiwan.
Reiping
R
Tang
Department of Public Health, Chang Gung University, Taoyuan 333, Taiwan.
Ling-Ling
LL
Hsieh
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Jy-Ming
JM
Chiang
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Wen-Sy
WS
Tsai
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Chien-Yuh
CY
Yeh
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Pao-Shiu
PS
Hsieh
Pathology Core of the Chang Gung Molecular Medicine Research Center, Taoyuan 333, Taiwan.
Ying
Y
Liang
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Jinn-Shiun
JS
Chen
Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Jau-Song
JS
Yu
D015703:Antigens, CD / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D058851:GPI-Linked Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055571:Secretory Pathway; D059470:Tetraspanins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D059470:Tetraspanins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C484065:NGFR protein, human; C499380:TACSTD2 protein, human; C115729:TSPAN6 protein, human