Effects of infiltrating lymphocytes and estrogen receptor on gene expression and prognosis in breast cancer
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The involvement of the immune system for the course of breast cancer, as evidenced by varying degrees of lymphocyte infiltration (LI) into the tumor is still poorly understood. The aim of this study was to evaluate the prognostic value of LI in breast cancer samples using microarray-based screening for LI-associated genes. Starting from the observation that most published ER gene signatures are heavily influenced by the LI effect, we developed and applied a novel approach to dissect molecular signatures. Further, a meta-analysis encompassing 1,044 hybridizations showed that LI alone is not sufficient to highlight breast cancer patients with different prognosis. However, for ER positive patients, high LI was associated with shorter survival times, whereas for ER negative patients, high LI is significantly associated with longer survival. Annotation of LI, in addition to ER status, is important for breast cancer patient prognosis and may have implications for the future treatment of breast cancer.
KeywordsBreast cancer Computational microdissection Prognosis Lymphocyte infiltration Estrogen receptor
We thank Sabrina Balaguer-Puig for excellent technical assistance, Andreas Buness for retrieving the external datasets and Dirk Ledwinka for IT support. The study was supported by a grant of the German Federal Ministry for Education and Research (NGFN grant 01GR0418; NGFN grant 01GR0450) and the Austrian Genome Research Program (GEN-AU).
MS, RK and TB had the initial ideas for the study. AC collected all the data and performed the experiments. TB did the statistical analysis with the help of AC and AB. MA, FP, KZ and HSa collected and reevaluated the patient samples creating the patient samples and annotation for our own dataset. AC, TB, RK, AP and HSü interpreted the results and wrote the manuscript. AC, RK, TB, AP and HSü contributed in discussions. All authors read and approved the final manuscript.
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