Finally, the association of our gene sets with outcome using distant metastasis free survival as an endpoint and 10 year censoring was analyzed. The survival analysis mean was performed in all tumors for which DMFS follow up is available, as well as in 21 groups that were stratified based on gene expression subtypes, Inhibitors,Modulators,Libraries ER status, lymph node status, histological this breast cancer data set. Here, we analyzed two sets of genes, namely the SRF Mkl1 induced gene set and the SAP dependent gene set containing tenascin C. The analysis was performed across tumor samples stratified according to PAM50 subtypes, estrogen receptor status and histological Inhibitors,Modulators,Libraries grade. In contrast to the SRF Mkl1 target genes that were predom inantly associated with tumors classified as normal like grade, and treatment status.
Inhibitors,Modulators,Libraries Samples in the whole cancer data set were stratified into three quan tiles, low, intermediate and high, based on SRF dependent SAP independent or SRF independent SAP dependent gene expression. Interestingly, high expression of SRF Mkl1 induced genes was associated with a better clinical out come for all tumors, as well as for LN negative and untreated tumors compared to low and intermediate ex pression of these genes. In contrast, both high and intermediate expression of the SAP dependent genes was associated with bad clinical outcome in all tumors, and particularly in LN negative, systemically untreated, ER positive, Grade 1 and 2 tumors. Similar re sults were obtained for the typical breast cancer gene CCNB1 by Ringn��r et al.The Kaplan Meier survival analyses were supported by the corresponding multivariate analyses.
The hazard ratio for the variate Grade shows statistical significance, proving that the in fluence of high SAP dependent gene expression on pa tient survival is independent of tumor grade. Among all tumors for which DMFS data are available, a hazard ra tio of 0. 44 for the low SRF independent SAP dependent tercile was detected compared to Inhibitors,Modulators,Libraries the high SRF independent SAP dependent tercile. This indicates that patients with tumors expressing high levels of the SAP dependent genes are more than twice as likely to develop metastatic disease. Similar hazard ratios, in the range of 0. 28 0. 44 for the low tercile compared to the high tercile Inhibitors,Modulators,Libraries were also detected among subgroups of untreated, LN negative, ER positive, Grade 1 and 2 tumors.
Thus, the association of high SRF independent SAP dependent gene expression with reduced DMFS among patients not receiving adjuvant therapy, as well as among LN negative, ER positive, Grade 1 and 2 patients indicates that in creased expression of the SAP Breast cancer dependent Mkl1 target genes plays a significant role in the natural metastatic progression of non aggressive towards highly aggressive breast cancer in human patients.
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