p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial Journal Article
| Authors: | Sonnenblick, A.; Salgado, R.; Brohée, S.; Zahavi, T.; Peretz, T.; Van Den Eynden, G.; Rouas, G.; Salmon, A.; Francis, P. A.; Di Leo, A.; Crown, J. P. A.; Viale, G.; Daly, L.; Javdan, B.; Fujisawa, S.; De Azambuja, E.; Lieveke, A.; Piccart, M. J.; Bromberg, J. F.; Sotiriou, C. |
| Article Title: | p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial |
| Abstract: | In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression signature identified patients with a good prognosis irrespective of the luminal subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer. |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; protein phosphorylation; aged; major clinical study; overall survival; cancer recurrence; disease free survival; chemotherapy; follow up; stat3 protein; breast cancer; gene expression; gene expression profiling; tumor volume; cohort analysis; immunofluorescence test; tissue microarray; estrogen receptor; adjuvant; tyrosine phosphorylation; prognostic marker; cancer prognosis; estrogen receptor positive breast cancer; luminal a breast cancer; human; female; priority journal; article; luminal b breast cancer; luminal cancer; signal transducer and activator of transcription 3; stat3 gene |
| Journal Title: | International Journal of Oncology |
| Volume: | 52 |
| Issue: | 2 |
| ISSN: | 1019-6439 |
| Publisher: | Spandidos Publications |
| Date Published: | 2018-02-01 |
| Start Page: | 424 |
| End Page: | 432 |
| Language: | English |
| DOI: | 10.3892/ijo.2017.4212 |
| PROVIDER: | scopus |
| PUBMED: | 29207087 |
| PMCID: | PMC6903891 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2018 -- Source: Scopus |
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