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Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery

Open access
Zou, Yutian, Xie, Jindong, Zheng, Shaoquan, Liu, Wenqing, Tang, Yuhui, Tian, Wenwen, Deng, Xinpei, Wu, Linyu, Zhang, Yue, Wong, Chau-Wei, Tan, Duxun, Liu, Qing, Xie, Xiaoming·2022·International Journal of Surgery

Abstract

BACKGROUND: Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there is a lack of an ideal predictive model for the progression and drug sensitivity of postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play an important role in tumor progression, which has the potential to be a prognostic and drug sensitivity indicator for TNBC after surgery. MATERIALS AND METHODS: Twelve PCD patterns (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis) were analyzed for model construction. Bulk transcriptome, single-cell transcriptome, genomics, and clinical information were collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, and KM-plotter cohorts to validate the model. RESULTS: The machine learning algorithm established a cell death index (CDI) with a 12-gene signature. Validated in five independent datasets, TNBC patients with high CDI had a worse prognosis after surgery. Two molecular subtypes of TNBC with distinct vital biological processes were identified by an unsupervised clustering model. A nomogram with high predictive performance was constructed by incorporating CDI with clinical features. Furthermore, CDI was associated with immune checkpoint genes and key tumor microenvironment components by integrated analysis of bulk and single-cell transcriptome. TNBC patients with high CDI are resistant to standard adjuvant chemotherapy regimens (docetaxel, oxaliplatin, etc.); however, they might be sensitive to palbociclib (an FDA-approved drug for luminal breast cancer). CONCLUSION: Generally, we established a novel CDI model by comprehensively analyzing diverse cell death patterns, which can accurately predict clinical prognosis and drug sensitivity of TNBC after surgery. A user-friendly website was created to facilitate the application of this prediction model (https://tnbc.shinyapps.io/CDI_Model/).

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Metadata

Authors
Zou, Y., Xie, J., Zheng, S., Liu, W., Tang, Y., Tian, W., Deng, X., Wu, L., Zhang, Y., Wong, C.-W., Tan, D., Liu, Q., & Xie, X.
Venue
International Journal of Surgery
Published
2022-11
Volume
107
Pages
106936
ISSN
  • 1743-9159 (ISSN-L)
  • 1743-9191
OpenAlex
W4296445148
Cited by
426
References
59
FWCI
32.89
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery. https://app.cochat.ai/papers/10.1016/j.ijsu.2022.106936
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Zou, Y., Xie, J., Zheng, S., Liu, W., Tang, Y., Tian, W., Deng, X., Wu, L., Zhang, Y., Wong, C.-W., Tan, D., Liu, Q., & Xie, X. (2022). Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery. International Journal of Surgery. https://doi.org/10.1016/j.ijsu.2022.106936

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