Novel breast cancer biomarkers identified by integrative proteomic and gene expression mapping.
Proteomic and transcriptomic platforms both play important roles in cancer research, with differing strengths and limitations. Here, we describe a proteo-transcriptomic integrative strategy for discovering novel cancer biomarkers, combining the direct visualization of differentially expressed proteins with the high-throughput scale of gene expression profiling. Using breast cancer as a case example, we generated comprehensive two-dimensional electrophoresis (2DE)/mass spectrometry (MS) proteomic maps of cancer (MCF-7 and HCC-38) and control (CCD-1059Sk) cell lines, identifying 1724 expressed protein spots representing 484 different protein species. The differentially expressed cell-line proteins were then mapped to mRNA transcript databases of cancer cell lines and primary breast tumors to identify candidate biomarkers that were concordantly expressed at the gene expression level. Of the top nine selected biomarker candidates, we reidentified ANX1, a protein previously reported to be differentially expressed in breast cancers and normal tissues, and validated three other novel candidates, CRAB, 6PGL, and CAZ2, as differentially expressed proteins by immunohistochemistry on breast tissue microarrays. In total, close to half (4/9) of our protein biomarker candidates were successfully validated. Our study thus illustrates how the systematic integration of proteomic and transcriptomic data from both cell line and primary tissue samples can prove advantageous for accelerating cancer biomarker discovery.
Ou
Keli
K
Agenica Research Pte Ltd., National Cancer Centre of Singarope, and Genome Institute of Singapore, 11 Hospital Drive, Singapore 169610.
Yu
Kun
K
Kesuma
Djohan
D
Hooi
Michelle
M
Huang
Ning
N
Chen
Wei
W
Lee
Suet Ying
SY
Goh
Xin Pei
XP
Tan
Lay Keng
LK
Liu
Jia
J
Soon
Sou Yen
SY
Bin Abdul Rashid
Suhaimi
S
Putti
Thomas C
TC
Jikuya
Hiroyuki
H
Ichikawa
Tetsuo
T
Nishimura
Osamu
O
Salto-Tellez
Manuel
M
Tan
Patrick
P
D017305:Annexin A1 / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051347:CapZ Actin Capping Protein / Q000032:analysis / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000032:analysis / Q000235:genetics; D045744:Cell Line, Tumor; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis / Q000379:methods; D038203:alpha-Crystallin B Chain / Q000032:analysis / Q000235:genetics
D017305:Annexin A1; D014408:Biomarkers, Tumor; C495845:CAPZA2 protein, human; C059215:CRYAB protein, human; D051347:CapZ Actin Capping Protein; D020543:Proteome; D038203:alpha-Crystallin B Chain; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase