Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features.
To gain insight into the role of the CCN genes in human breast carcinomas, we quantified connective tissue growth factor (CTGF), WISP-1, CYR61, and human NOV (NOVH) mRNA expression levels in samples from 44 primary breast tumors and seven normal breasts using quantitative real-time PCR assay. Overexpression of CTGF, WISP-1, CYR61, and NOVH was found in 55 (24 of 44), 46 (20 of 44), 39 (17 of 44), and 11% (5 of 44) primary breast tumors, respectively. Statistical univariate analysis was performed to explore the links between expression of the CCN genes and clinical and pathological parameters. Interestingly, significant associations were found between CTGF expression versus stage, tumor size, lymph node status, and age at diagnosis; WISP-1 mRNA levels versus stage, tumor size, lymph node, and HER-2/neu overexpression; and CYR61 expression with stage, tumor size, lymph node, age, and estrogen receptor expression. In contrast to CTGF, WISP-1, and CYR61, no significant correlation was found between NOVH expression and any of the clinical and pathological factors. Furthermore, multivariate classification tree model analysis showed that stage and lymph node involvement were important for predicting CTGF expression in breast cancers; the stage, age, and HER-2/neu status were key factors for WISP-1 expression; and the stage, age, and estrogen receptor were valuable predictors for CYR61 expression. In summary, these results suggest that CTGF, WISP-1, and CYR61 may play a role in the progression of breast cancer and might serve as a valuable tool for monitoring tumor status of breast cancer patients.
Xie
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D
Division of Hematology/Oncology, Cedars-Sinai Medical Center, Department of Biomathematics, UCLA School of Medicine, Los Angeles, California 90048, USA. xied@ucla.edu
Nakachi
K
K
Wang
H
H
Elashoff
R
R
Koeffler
H P
HP
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D055511:CCN Intercellular Signaling Proteins; D055513:Connective Tissue Growth Factor; D055515:Cysteine-Rich Protein 61; D005260:Female; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D055514:Nephroblastoma Overexpressed Protein; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D055511:CCN Intercellular Signaling Proteins; C501848:CCN1 protein, human; C526317:CCN2 protein, human; C526319:CCN3 protein, human; C116396:CCN4 protein, human; D055515:Cysteine-Rich Protein 61; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D055513:Connective Tissue Growth Factor