Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray.
Estrogen receptor (ER) status is an essential determinant of clinical and biological behavior of human breast cancers. While ER-positive breast cancers respond well to adjuvant hormone therapy, ER-negative tumors are generally resistant. To date, no attempts have succeeded in finding molecular markers for classifying ER-negative breast cancers with respect to postoperative prognosis. To identify a set of prognostic markers for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of ten primary breast cancers from patients who had died of breast cancer within 5 years after surgery (5y-D) and 10 from patients who had survived disease-free for more than 5 years (5y-S). Sets of genes characterizing each group were identified by Mann-Whitney and random-permutation tests. We documented 71 genes with higher expression in the 5y-D group than in the 5y-S group, and 15 with higher expression in the 5y-S group than in the 5y-D group. Semi-quantitative RT-PCR experiments were carried out to confirm the results of the microarray analysis. We established a scoring system for predicting postoperative prognosis of ER-negative breast cancers on the basis of aberrant gene expression. The list of genes reported here provides valuable information with regard to progression of breast cancer and is a source of possible target molecules for development of novel drugs to treat patients with ER-negative breast cancers.
Nagahata
Takemitsu
T
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
Onda
Masamitsu
M
Emi
Mitsuru
M
Nagai
Hisaki
H
Tsumagari
Koji
K
Fujimoto
Takashi
T
Hirano
Akira
A
Sato
Takamichi
T
Nishikawa
Kiyohiro
K
Akiyama
Futoshi
F
Sakamoto
Goi
G
Kasumi
Fujio
F
Miki
Yoshio
Y
Tanaka
Toshihiro
T
Tsunoda
Tatsuhiko
T
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011184:Postoperative Period; D011379:Prognosis; D012334:RNA, Neoplasm / Q000032:analysis*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D017931:DNA Primers; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen