Biological and Clinical Significance of MAD2L1 and BUB1, Genes Frequently Appearing in Expression Signatures for Breast Cancer Prognosis.
To investigate the biologic relevance and clinical implication of genes involved in multiple gene expression signatures for breast cancer prognosis, we identified 16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1. These genes appeared in 5 signatures and were involved in cell-cycle regulation. We analyzed the expression of these genes in relation to tumor features and disease outcomes. In vitro experiments were also performed in two breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration and invasion after knocking down the expression of these genes. High expression of these genes was found to be associated with aggressive tumors and poor disease-free survival of 203 breast cancer patients in our study, and the association with survival was confirmed in an online database consisting of 914 patients. In vitro experiments demonstrated that lowering the expression of these genes by siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our investigation suggests that MAD2L1 and BUB1 may play important roles in breast cancer progression, and measuring the expression of these genes may assist the prediction of breast cancer prognosis.
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Zhanwei
Z
Wang
Department of Surgical Sciences, Gynecologic Oncology, Azienda Ospedaliero-Universitaria Città della Salute, Turin, Italy.
Dionyssios
D
Katsaros
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Yi
Y
Shen
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Yuanyuan
Y
Fu
Department of Surgical Sciences, Gynecologic Oncology, Azienda Ospedaliero-Universitaria Città della Salute, Turin, Italy.
Emilie Marion
EM
Canuto
Department of Surgical Sciences, Gynecologic Oncology, Azienda Ospedaliero-Universitaria Città della Salute, Turin, Italy.
Chiara
C
Benedetto
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America.
Lingeng
L
Lu
Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Wen-Ming
WM
Chu
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America.
Harvey A
HA
Risch
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Herbert
H
Yu
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D053208:Kaplan-Meier Estimate; D064246:Mad2 Proteins / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
D005819:Genetic Markers; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D034741:RNA, Small Interfering; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases