Construction and validation of a prognostic signature based on necroptosis-related genes in hepatocellular carcinoma

Peng, Yue-Ling; Wang, Lingxiao; Li, Mu-Ye; Liu, Liping; Li, Rong-Shan

doi:10.1371/journal.pone.0279744

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…The expression level of MFN2 is increased in osteosarcoma, and it can inhibit the immune system in osteosarcoma TIM. The level of ATP6V1E1 mRNA is downregulated in osteosarcoma, and the ATP6V1E1 mRNA expression dysregulation leads to immune imbalance in osteosarcoma 115,116 …”

Section: Mechanisms Of Cell Death In Osteosarcomamentioning

confidence: 99%

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

Liu,

Wang

et al. 2024

Cancer Medicine

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Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14–19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c‐Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/β‐catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.

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Section: Mechanisms Of Cell Death In Osteosarcomamentioning

confidence: 99%

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

Liu,

Wang

et al. 2024

Cancer Medicine

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“…At present, ferroptosis, pyroptosis and necroptosis are three highly studied types of NARCD in HCC development and treatment, and these influence the fate of cells in the liver (35)(36)(37)(38)(39)(40). There are some differences and similarities among these three types of NARCD, and the key features of ferroptosis, pyroptosis and necroptosis, including the morphological and biochemical features, key regulators, and related drugs are shown in Table I.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review)

Liu,

Yu,

Yan

et al. 2024

Int J Oncol

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Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multi-tyrosine kinase inhibitors approved for first-line therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of non-apoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune 'cold' tumors into immune 'hot' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.

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Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma

Zhu,

Huang,

Peng

et al. 2023

Front. Immunol.

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BackgroundPrevious studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).MethodsBased on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments.ResultsThis study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration.ConclusionPANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.

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Construction and validation of a prognostic signature based on necroptosis-related genes in hepatocellular carcinoma

Cited by 3 publications

References 40 publications

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

The role of programmed cell death in osteosarcoma: From pathogenesis to therapy

Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review)

Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma

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