Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes

Li, Qi; Liu, Hengchen; Jin, Yun; Yu, Yuanquan; Wang, Yihang; Wu, Di; Guo, Yinghao; Xi, Longfu; Ye, Dan; Pan, Yanzhi; Zhang, Xiaoxiao; Li, Jiangtao

doi:10.1016/j.compbiomed.2023.107370

Cited by 7 publications

(3 citation statements)

References 108 publications

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“…There are various cancers in which HHLA2 is expressed more frequently than PD-L1 [11,51,86]. According to many researchers, HHLA2 seems to be a promising target for immunotherapies in the cancers resistant to any PD-L1 therapies [45,89,95]. Considering the dual role of HHLA2, which is an effect of its interaction with two receptors, it is possible to unblock the immune system and stimulate it, enhancing the therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

“…Another study showed that a model, based on differently expressed genes related to ferroptosis may predict the long-term prognosis of patients with high accuracy. It has been shown that immune-related pathways take part in the process of ferroptosis and HHLA2, which was found to be differently expressed in breast cancer and could be involved in ferroptosis during the disease [45]. It is unclear whether HHLA2 has prognostic or therapeutic value in breast cancer.…”

Section: Hhla2 and Breast Cancermentioning

confidence: 99%

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The Importance of HHLA2 in Solid Tumors—A Review of the Literature

Kula,

Koszewska,

Kot

et al. 2024

Cells

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Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host’s immune mechanisms to inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, and its ligand PD-L1 are used in various cancer therapies. However, the most thoroughly researched pathway targeting PD-1/PD-L1 has many limitations, and multiple malignancies resist its effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) is the youngest known molecule from the B7 family. HHLA2/TMIGD2/KIRD3DL3 is one of the critical pathways in modulating the immune response. Recent studies have demonstrated that HHLA2 has a double effect in modulating the immune system. The connection of HHLA2 with TMIGD2 induces T cell growth and cytokine production via an AKT-dependent signaling cascade. On the other hand, the binding of HHLA2 and KIR3DL3 leads to the inhibition of T cells and mediates tumor resistance against NK cells. This review aimed to summarize novel information about HHLA2, focusing on immunological mechanisms and clinical features of the HHLA2/KIR3DL3/TMIGD2 pathway in the context of potential strategies for malignancy treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Hhla2 and Breast Cancermentioning

confidence: 99%

The Importance of HHLA2 in Solid Tumors—A Review of the Literature

Kula,

Koszewska,

Kot

et al. 2024

Cells

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“…Breast cancer, the most prevalent malignant tumor globally and remains the major cause of cancer‐related mortality among women globally 1,2 . Neoadjuvant chemotherapy (NAC) represents a standard therapeutic approach for cases with locally advanced breast cancer 3 .…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐based radiomics‐clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer

Li,

Wu,

Lin

et al. 2024

J of Clinical Ultrasound

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PurposeTo assess the predictive value of an ultrasound‐based radiomics‐clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients.MethodsThis retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram.ResultsA total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound‐based radiomics‐clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort.ConclusionsUltrasound‐based radiomics‐clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

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Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells

Zhu,

Luo,

Zhao

et al. 2024

Nat. Prod. Bioprospect.

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Cancer cells generally exhibit ‘iron addiction’ phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic ‘ballooning’ phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death. Graphical Abstract

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Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes

Cited by 7 publications

References 108 publications

The Importance of HHLA2 in Solid Tumors—A Review of the Literature

The Importance of HHLA2 in Solid Tumors—A Review of the Literature

Ultrasound‐based radiomics‐clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer

Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells

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