Development and validation of prognostic gene signature for basal-like breast cancer and high-grade serous ovarian cancer.

Autor: Zhang Y; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA., Liu J; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA., Raj-Kumar PK; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA., Sturtz LA; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA., Praveen-Kumar A; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA., Yang HH; Center for Cancer Research, National Cancer Institute, Rockville, MD, USA., Lee MP; Center for Cancer Research, National Cancer Institute, Rockville, MD, USA., Fantacone-Campbell JL; Murtha Cancer Center Research Program, Bethesda, MD, USA.; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Walter Reed National Military Medical Center, Bethesda, MD, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA., Hooke JA; Murtha Cancer Center Research Program, Bethesda, MD, USA.; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Walter Reed National Military Medical Center, Bethesda, MD, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA., Kovatich AJ; Murtha Cancer Center Research Program, Bethesda, MD, USA.; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Walter Reed National Military Medical Center, Bethesda, MD, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA., Shriver CD; Murtha Cancer Center Research Program, Bethesda, MD, USA.; Uniformed Services University of the Health Sciences, Bethesda, MD, USA.; Walter Reed National Military Medical Center, Bethesda, MD, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA., Hu H; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, USA. h.hu@wriwindber.org.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2020 Dec; Vol. 184 (3), pp. 689-698. Date of Electronic Publication: 2020 Sep 02.
DOI: 10.1007/s10549-020-05884-z
Abstrakt: Purpose: Molecular similarities have been reported between basal-like breast cancer (BLBC) and high-grade serous ovarian cancer (HGSOC). To date, there have been no prognostic biomarkers that can provide risk stratification and inform treatment decisions for both BLBC and HGSOC. In this study, we developed a molecular signature for risk stratification in BLBC and further validated this signature in HGSOC.
Methods: RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA) project for 190 BLBC and 314 HGSOC patients. Analyses of differentially expressed genes between recurrent vs. non-recurrent cases were performed using different bioinformatics methods. Gene Signature was established using weighted linear combination of gene expression levels. Their prognostic performance was evaluated using survival analysis based on progression-free interval (PFI) and disease-free interval (DFI).
Results: 63 genes were differentially expressed between 18 recurrent and 40 non-recurrent BLBC patients by two different methods. The recurrence index (RI) calculated from this 63-gene signature significantly stratified BLBC patients into two risk groups with 38 and 152 patients in the low-risk (RI-Low) and high-risk (RI-High) groups, respectively (p = 0.0004 and 0.0023 for PFI and DFI, respectively). Similar performance was obtained in the HGSOC cohort (p = 0.0131 and 0.004 for PFI and DFI, respectively). Multivariate Cox regression adjusting for age, grade, and stage showed that the 63-gene signature remained statistically significant in stratifying HGSOC patients (p = 0.0005).
Conclusion: A gene signature was identified to predict recurrence in BLBC and HGSOC patients. With further validation, this signature may provide an additional prognostic tool for clinicians to better manage BLBC, many of which are triple-negative and HGSOC patients who are currently difficult to treat.
Databáze: MEDLINE
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