A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
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Purpose Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
Abstract
Purpose Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
참고문헌 (29)
- Global Burden of Disease Cancer Collaboration, "Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016 : a systematic analysis for the Global Burden of Disease Study", JAMA Oncol, 4, pp.1553~1568 (2018)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Hong S, "Cancer statistics in Korea : incidence, mortality, survival, and prevalence in 2017", Cancer Res Treat, 52, pp.335~350 (2020)
- Allemani C, "Global surveillance of trends in cancer survival 2000-14(CONCORD-3) : analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries", Lancet, 391, pp.1023~1075 (2018)
- Sparano JA, "Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer", N Engl J Med, 379, pp.111~121 (2018)
- Henry NL, "Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer : update of the ASCO endorsement of the cancer care Ontario guideline", J Clin Oncol, 37, pp.1965~1977 (2019)
- Carey LA, "The triple negative paradox : primary tumor chemo-sensitivity of breast cancer subtypes", Clin Cancer Res, 13, pp.2329~2334 (2007)
- Burstein MD, "Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer", Clin Cancer Res, 21, pp.1688~1698 (2015)
- Liu YR, "Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer", Breast Cancer Res, 18, pp.33~ (2016)
- Garrido-Castro AC, "Insights into molecular classifications of triple-negative breast cancer : improving patient selection for treatment", Cancer Discov, 9, pp.176~198 (2019)
- Tutt A, "Carboplatin in BRCA1", 2-mutated and triple-negative breast cancer BRCAness subgroups : the TNT Trial, 2018, pp.24, 628~637
- Prat A, "Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer", Breast Cancer Res, 12, pp.R68~ (2010)
- Kim J, "Genomic characteristics of triple-negative breast cancer nominate molecular subtypes that predict chemotherapy response", Mol Cancer Res, 18, pp.253~263 (2020)
- Lehmann BD, "Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies", J Clin Invest, 121, pp.2750~2767 (2011)
- Perou CM, "Molecular portraits of human breast tumours", Nature, 406, pp.747~752 (2000)
- Park J, "Nonphosphorylatable PEA15 mutant inhibits epithelial-mesenchymal transition in triple-negative breast cancer partly through the regulation of IL-8 expression", Breast Cancer Res Treat, 189, pp.333~345 (2021)
- Sukumar J, "Triple-negative breast cancer : promising prognostic biomarkers currently in development", Expert Rev Anticancer Ther, 21, pp.135~148 (2021)
- Wolff AC, "Recommendations for human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists clinical practice guideline update, 2013, pp.31, 3997~4013
- Allison KH, "Estrogen and progesterone receptor testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists guideline update, 2020, pp.144, 545~563
- Varley KE, "Recurrent read-through fusion transcripts in breast cancer", Breast Cancer Res Treat, 146, pp.287~297 (2014)
- Park IJ, "A nine-gene signature for predicting the response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer", Cancers(Basel), 12, pp.800~ (2020)
- Lehmann BD, "Refinement of triple-negative breast cancer molecular subtypes : implications for neoadjuvant chemotherapy selection", PLoS One, 11, pp.e0157368~ (2016)
- Bolotin DA, "Antigen receptor repertoire profiling from RNA-seq data", Nat Biotechnol, 35, pp.908~911 (2017)
- Han J, "TCR repertoire diversity of peripheral PD-1(+)CD8(+)T cells predicts clinical outcomes after immunotherapy in patients with non-small cell lung cancer", Cancer Immunol Res, 8, pp.146~154 (2020)
- Cui JH, "TCR repertoire as a novel indicator for immune monitoring and prognosis assessment of patients with cervical cancer", Front Immunol, 9, pp.2729~ (2018)
- Burstein MD, "Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer", Clin Cancer Res, 21, pp.1688~1698 (2015)
- Masuda H, "Changes in triple-negative breast cancer molecular subtypes in patients without pathologic complete response after neoadjuvant systemic chemotherapy", JCO Precis Oncol, 6, pp.e2000368~ (2022)
- Masuda N, "Adjuvant capecitabine for breast cancer after preoperative chemotherapy", N Engl J Med, 376, pp.2147~2159 (2017)
- Schmid P, "Pembrolizumab for early triple-negative breast cancer", N Engl J Med, 382, pp.810~821 (2020)