Ferroptosis Markers Predict the Survival, Immune Infiltration, and Ibrutinib Resistance of Diffuse Large B cell Lymphoma

Weng, Junmei; Chen, Lian; Liu, Huicheng; Xiang, Yang; Huang, Liu

doi:10.1007/s10753-021-01609-6

Cited by 20 publications

(11 citation statements)

References 49 publications

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“…There is rich literature available substantiating the predictive value of inflammatory markers, including PLR, NLR, LMR, and SII in solid tumors (breast tumors, lung cancer, etc.) and diffuse large B cell lymphoma (DLBCL) (23)(24)(25)(26)(27)(28). High NLR and SII are poor prognostic factors for tumors.…”

Section: Discussionmentioning

confidence: 99%

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study

Wen

Zhao

et al. 2023

Front. Oncol.

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BackgroundThe present study sought to understand how clinical factors and inflammatory biomarkers affected the prognosis of mucosa-associated lymphoid tissue (MALT) lymphoma and develop a predictive nomogram to assist in clinical practice.MethodsWe conducted a retrospective study on 183 cases of newly diagnosed MALT lymphoma from January 2011 to October 2021, randomly divided into two groups: a training cohort (75%); and a validation cohort (25%). The least absolute shrinkage and selection operator (LASSO) regression analysis was combined with multivariate Cox regression analysis to construct a nomogram for predicting the progression-free survival (PFS) in patients with MALT lymphoma. To evaluate the accuracy of the nomogram model, the area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used.ResultsThe PFS was significantly associated with the Ann Arbor Stage, targeted therapy, radiotherapy, and platelet-to-lymphocyte ratio (PLR) in MALT lymphoma. These four variables were combined to establish a nomogram to predict the PFS rates at three and five years. Importantly, our nomogram yielded good predictive value with area under the ROC curve (AUC) values of 0.841 and 0.763 in the training cohort and 0.860 and 0.879 in the validation cohort for the 3-year and 5-year PFS, respectively. Furthermore, the 3-year and 5-year PFS calibration curves revealed a high degree of consistency between the prediction and the actual probability of relapse. Additionally, DCA demonstrated the net clinical benefit of this nomogram and its ability to identify high-risk patients accurately.ConclusionThe new nomogram model could accurately predict the prognosis of MALT lymphoma patients and assist clinicians in designing individualized treatments.

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Section: Discussionmentioning

confidence: 99%

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study

Wen

Zhao

et al. 2023

Front. Oncol.

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“…CXCL12 regulates neoangiogenesis, tumor cell proliferation, and migration of various solid tumors by binding to chemokine 4 (CXCL4)[ 15 ]. Blocking the CXCL12/CXCL4 pathway can enhance tumor T-cell infiltration, reduce regulatory T-cell production, and enhance antitumor activity[ 16 ]. CXCL12 expression was markedly heterogeneous in different tumors, indicating the importance of exploring CXCL12 expression in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

Wu¹,

Sun²,

Ouyang³

2022

World J Clin Cases

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BACKGROUND The effects of T-cell immunoglobulin mucin molecule-3 (Tim-3), transforming growth factor β (TGF-β), and chemokine-12 (CXCL12) expression on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) have not been elucidated. AIM To examine the correlation between Tim-3, TGF-β and CXCL12 expression and DLBCL prognosis. METHODS Lymph node tissues of 97 patients with DLBCL and 93 normal-response hyperplastic lymph node tissues treated from January 2017 to May 2019 were selected as the DLBCL and control groups, respectively. The expression of Tim-3, TGF-β, and CXCL12 was detected immunohistochemically. Patients were followed up for 3 years, and progression-free survival was recorded. Cox multifactorial analysis was performed to analyze the risk factors for poor prognosis. RESULTS The positive expression rates of Tim-3, TGF-β, and CXCL12 were higher in DLBCL tissues than in non-cancerous (control) tissues ( P < 0.05). One-year post-surgery, the positive expression rates of Tim-3, TGF-β, and CXCL12 were higher in patients with effective treatment than in those with ineffective treatment ( P < 0.05). The 3-year progression-free survival of 97 patients with DLBCL was 67.01% (65/97). Univariate analysis revealed that clinical stage, bone marrow infiltration, International Prognostic Index (IPI) score, Tim-3 positivity, TGF-β positivity, and CXCL12 positivity were associated with poor prognosis ( P < 0.05). Multivariate Cox regression analysis demonstrated that clinical stage III–IV, bone marrow infiltration, mediate-to-high-risk IPI scores, Tim-3 positivity, TGF-β positivity, and CXCL12 positivity were independent risk factors affecting prognosis ( P < 0.05). CONCLUSION DLBCL tissues exhibit high positive expression of Tim-3, TGF-β, and CXCL12, and a high expression of all three indicates a poor prognosis.

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“…Huan Chen et al (2021b) performed a systematic study and identified a ferroptosis-related gene signature comprising 8 genes that could be used to divide DLBCL patients into high- and low-risk groups. Moreover, Junmei Weng et al built a risk score model related to ferroptosis with 11 genes and revealed that the high-risk score group showed resistance to ibrutinib treatment, while ferroptosis inducer, acetaminophen, inhibited the expression of the high-risk genes in the DLBCL cell lines ( Weng et al, 2022 ). Julie Devin et al (2022) built the iron score-related model to identify patients with DLBCL showing poor prognosis who might benefit from treatment targeted to maintaining iron homeostasis.…”

Section: Potential Role Of Ferroptosis In Lymphomamentioning

confidence: 99%

Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach

Zhou

Qin

et al. 2022

Front. Genet.

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Unlike apoptosis, necroptosis, autophagy, and pyroptosis, ferroptosis represents a new type of cell death, which is characterized by iron-dependent lipid peroxidation. This process relies largely on the metabolite reactive oxygen species (ROS), phospholipids containing polyunsaturated fatty acids (PUFA-PL), transition metal iron, intra-, and intercellular signaling events, and environmental stress that regulate cellular metabolism and ROS levels. Recent studies show that ferroptosis plays an important role in tumorigenesis, tumor development, and the treatment of hematological malignancies, including lymphoma. Despite the constant emergence of new drugs, the differences in morphological features, immunophenotypes, biological patterns, rates of onset, and response to treatment in lymphoma pose major therapeutic challenges. Since lymphoma is associated with ferroptosis and shows sensitivity towards it, targeting the potential regulatory factors may regulate lymphoma progression. This has emerged as a research hotspot. This review summarizes the current knowledge on ferroptosis induction and resistance mechanisms, their roles and mechanistic details of ferroptosis in lymphoma suppression and immunity, and finally the treatment strategies for lymphoma by targeting ferroptosis.

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Ferroptosis Markers Predict the Survival, Immune Infiltration, and Ibrutinib Resistance of Diffuse Large B cell Lymphoma

Cited by 20 publications

References 49 publications

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study

T-cell immunoglobulin mucin molecule-3, transformation growth factor β, and chemokine-12 and the prognostic status of diffuse large B-cell lymphoma

Ferroptosis in lymphoma: Emerging mechanisms and a novel therapeutic approach

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