TY - JOUR
T1 - Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor
AU - Minemura, Hiroyuki
AU - Takagi, Kiyoshi
AU - Miki, Yasuhiro
AU - Shibahara, Yukiko
AU - Nakagawa, Saki
AU - Ebata, Akiko
AU - Watanabe, Mika
AU - Ishida, Takanori
AU - Sasano, Hironobu
AU - Suzuki, Takashi
N1 - Publisher Copyright:
© 2015 Japanese Cancer Association.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non-protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stage IV breast carcinoma tissues, comparing stage I-III cases by miRNA PCR array, and identified miR-1 as the miRNA which was the most associated with the distant metastasis. However, miR-1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR-1 expression in breast carcinoma using in situ hybridization (ISH). miR-1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non-neoplastic mammary glands or stroma. miR-1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki-67 in breast carcinoma. Moreover, the miR-1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease-free and breast cancer-specific survival. These findings suggest that abnormal miR-1 expression is associated with an aggressive phenotype of breast carcinoma and that miR-1 status is a potent prognostic factor in human breast cancer patients. This is the first report that examined miR-1 in breast carcinoma tissue. Our present results suggest that miR-1 is a potent prognostic marker and it might become an important therapeutic target of breast cancer patients.
AB - Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non-protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stage IV breast carcinoma tissues, comparing stage I-III cases by miRNA PCR array, and identified miR-1 as the miRNA which was the most associated with the distant metastasis. However, miR-1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR-1 expression in breast carcinoma using in situ hybridization (ISH). miR-1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non-neoplastic mammary glands or stroma. miR-1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki-67 in breast carcinoma. Moreover, the miR-1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease-free and breast cancer-specific survival. These findings suggest that abnormal miR-1 expression is associated with an aggressive phenotype of breast carcinoma and that miR-1 status is a potent prognostic factor in human breast cancer patients. This is the first report that examined miR-1 in breast carcinoma tissue. Our present results suggest that miR-1 is a potent prognostic marker and it might become an important therapeutic target of breast cancer patients.
KW - Breast cancer
KW - MicroRNA
KW - PCR array
KW - Prognosis
KW - in situ hybridization
UR - http://www.scopus.com/inward/record.url?scp=84983193998&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983193998&partnerID=8YFLogxK
U2 - 10.1111/cas.12808
DO - 10.1111/cas.12808
M3 - Article
C2 - 26331797
AN - SCOPUS:84983193998
VL - 106
SP - 1642
EP - 1650
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 11
ER -