Detection of breast cancer by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry tissue and serum protein profiling.
OBJECTIVE
Novel diagnostic breast cancer markers have been extensively searched for in the proteome, using, among others, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Thus far, the majority of SELDI-TOF MS studies have investigated samples originating from biorepositories, which hampers biomarker discovery as they likely suffer from variable adherence to collection protocols.


METHODS
We investigated breast cancer (n=75) and control (n=26) serum and tissue samples, collected prospectively by rigorous adherence to a strictly defined protocol. Sera were collected preoperatively and postoperatively, and serum and tissue samples were analyzed by SELDI-TOF MS using the IMAC30 Ni and Q10 pH 8 array.


RESULTS
Three serum peaks were significantly associated with breast cancer, while in tissue, 27 discriminative peaks were detected. Several peak clusters gradually increased or decreased in intensity from healthy to benign to cancer, or with increasing cancer stage. The constructed classification trees had a tenfold cross-validated performance of 67% to 87%. Two tissue peaks were identified as N-terminal albumin fragments. These are likely to have been generated by (breast) cancer-specific proteolytic activity in the tumor microenvironment.


CONCLUSIONS
These albumin fragment scan potentially provide insights into the pathophysiological mechanisms associated with, or underlying, breast cancer, and aid in improving breast cancer diagnosis.
Gast
Marie-Christine W
MC
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands. Marie-Christine.Gast@slz.nl
van Dulken
Eric J
EJ
van Loenen
Thea K G
TK
Kingma-Vegter
Florine
F
Westerga
Johan
J
Flohil
Claudie C
CC
Knol
Jaco C
JC
Jimenez
Connie R
CR
van Gils
Carla H
CH
Wessels
Lodewijk F A
LF
Schellens
Jan H N
JH
Beijnen
Jos H
JH
D000368:Aged; D001798:Blood Proteins / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D003953:Diagnosis-Related Groups; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D001798:Blood Proteins