The HCCR oncoprotein as a biomarker for human breast cancer.
OBJECTIVE
HCCR oncoprotein is reported to be related to tumorigenesis, including breast cancer, functioning as a negative regulator of p53. Mice transgenic for HCCR developed breast cancers. The objective of this study was to validate the HCCR oncoprotein as a candidate biomarker for breast cancer.


METHODS
HCCR expression in breast cancer cells was analyzed by quantitative PCR, ELISA, immunohistochemistry, Western blotting, fluorescence-activated cell sorting, and confocal microscopy. Epitope areas were determined using mass spectrometry through the analysis of time-dependent tryptic fragment patterns of HCCR. HCCR expression profiles in breast cancer patient sera were analyzed, and correlations with clinicopathologic data and carbohydrate antigen 15-3 (CA15-3) levels were determined.


RESULTS
HCCR was up-regulated in breast cancer cells and tissues. The epitope regions of HCCR recognized by monoclonal antibody (BCS-1) were HFWTPK and QQTDFLDIYHAFR. According to fluorescence-activated cell sorting and confocal microscopic analysis, BCS-1 was bound to HCCR antigen on the cell surface. Serum HCCR concentrations were measured using ELISA from 299 subjects, including 129 patients with breast cancer, 24 patients with benign breast disease, and 158 normal volunteers, and comparisons were made to CA15-3. Serologic studies revealed an 86.8% sensitivity for HCCR in breast cancer, which was higher than 21.0% for CA15-3. Eighty-six of 98 (87.8%) patients with breast cancers that were negative for CA15-3 were positive for HCCR-1. A positive response rate of 83.3% was identified even at early stages for pathologic factors in breast cancer.


CONCLUSIONS
The HCCR assay has an advantage over CA15-3 in diagnosing breast cancer and detecting early stages of the disease.
Jung
Sang Seol
SS
Department of Surgery, The Catholic University of Korea, Seoul.
Park
Hyung Soon
HS
Lee
Insong James
IJ
Namkoong
Hong
H
Shin
Seung Min
SM
Cho
Goang Won
GW
Ha
Seon-Ah
SA
Park
Yong Gyu
YG
Lee
Youn Soo
YS
Ko
Jesang
J
Kim
Jin Woo
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D008875:Middle Aged; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012680:Sensitivity and Specificity; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology; D015854:Up-Regulation
D000906:Antibodies; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000939:Epitopes; C476732:LETMD1 protein, human; D018396:Mucin-1; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D014357:Trypsin