Definition of a Novel Immunogenic Cell Death-Relevant Gene Signature Associated with Immune Landscape in Gastric Cancer

Meng, Yajun; Jin, Ze; Wang, Mengmeng; Chen, Di; Zhu, Mengpei; Huang, Yumei; Xia, Shang; Xiong, Zhifang

doi:10.1007/s10528-023-10361-5

Cited by 5 publications

(1 citation statement)

References 60 publications

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“…[2] Recent studies have reinforced the notion that the immune system plays a vital role in the initiation and progression of tumors and that there exists a close interdependence between tumor prognosis and the immune status of an individual. [3] Immune-based interventions in the form of immunotherapy have emerged as cutting-edge approaches for tumor prognosis and treatment. Immunotherapy is a therapeutic approach that harnesses a patient's immune system to recognize and combat tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis

Yang

Qian

et al. 2023

Medicine

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Head and neck squamous cell carcinoma (HNSCC) is a malignancy commonly found in the head and neck region, with a low 5-year survival rate. Although immunotherapy has made significant progress, its efficacy in HNSCC treatment remains unsatisfactory. Killer cell lectin-like receptor K1 (KLRK1), a marker highly expressed in immune cells, can bind to its ligands expressed by cancer cells to exert its antitumor effect. However, the role of KLRK1 in HNSCC has yet to be studied extensively. This study aimed to explore the involvement of KLRK1 in immune infiltration of HNSCC and its correlation with prognosis. We analyzed KLRK1 expression data from the Cancer Genome Atlas database. The relationship between KLRK1 and immune cell infiltration has also been investigated. Finally, we analyzed the association between the expression of KLRK1 and its ligands and the prognosis of patients with HNSCC. We found that KLRK1 was highly expressed in HNSCC and correlated with better prognosis. KLRK1 expression was correlated with age, histological grade, HPV infection, pT, pN, pTNM stage, primary site, and survival status. High expression levels of KLRK1 have been linked to high levels of immune cell infiltration, particularly CD4/8 (+) T lymphocytes. Among the ligands of KLRK1, UL16 binding protein (ULBP) 1-3 showed high expression, which was associated with an increased risk of death. Notably, the expression of KLRK1 was negatively correlated with ULBP1-3. Patients with high levels of ULBP2/3 expression in tonsil carcinoma had poorer prognosis than those with low levels (P < .01), whereas ULBP1 expression levels had no significant effect on tonsil carcinoma prognosis (P = .770). The expression levels of ULBP1/3 were correlated with worse prognosis in patients with laryngeal cancer (P < .05), whereas there was no significant correlation between ULBP2 expression levels and overall survival (P = .269). Our study revealed that KLRK1 is highly expressed in HNSCC and is associated with a better prognosis and immune infiltration. Patients with high expression of KLRK1 ligands exhibited worse prognoses, possibly because of the expression of more soluble ligands.

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Section: Introductionmentioning

confidence: 99%

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis

Yang

Qian

et al. 2023

Medicine

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Immunogenic cell death–related genes predict prognosis and response to immunotherapy in lung squamous cell carcinoma

Li,

Chen,

Dong

et al. 2024

Biotech and App Biochem

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Lung squamous cell carcinoma (LUSC) is a malignancy with limited therapeutic options. Immunogenic cell death (ICD) has the potential to enhance the efficacy of cancer therapy by triggering immune responses. We aimed to explore the potential of ICD‐based classification in predicting prognosis and response to immunotherapy for LUSC. RNA‐seq information and clinical data of LUSC patients were obtained from The Cancer Genome Atlas (TCGA) dataset. ICD‐related gene expressions in LUSC samples were analyzed by consensus clustering. Subsequently, differentially expressed genes (DEGs) between different ICD‐related subsets were analyzed. Tumor mutation burden, immune cell infiltration, and survival analyses were conducted between different ICD subsets. Finally, an ICD‐related risk signature was constructed and evaluated in LUSC patients, and the immunotherapy responses based on the gene expressions were also forecasted. ICD‐high and ICD‐low groups were defined, and 1466 DEGs were identified between the two subtypes. These DEGs were mainly enriched in collagen‐containing extracellular matrix, cytokine–cytokine receptor interaction, the PI3K‐Akt signaling pathway, and neuroactive ligand–receptor interaction. Furthermore, the ICD‐low group exhibited a favorable prognosis, enhanced TTN and MUC16 mutation frequencies, increased infiltrating immune cells, and downregulated immune checkpoint expressions. Furthermore, we demonstrated that an ICD‐related model (based on CD4, NLRP3, NT5E, and TLR4 genes) could forecast the prognosis of LUSC, and ICD risk scores were lower in the responder group. In summary, the predicted values of ICD‐related genes (CD4, NLRP3, NT5E, and TLR4) for the prognosis and response to immunotherapy in LUSC were verified in the study, which benefits immunotherapy‐based interventions for LUSC patients.

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Unraveling the immunogenic cell death pathways in gastric adenocarcinoma: A multi‐omics study

Gu,

Chen,

Dong

et al. 2024

Environmental Toxicology

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BackgroundGastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal (GI) system. However, the lack of reliable biomarkers has made its diagnosis, prognosis, and treatment challenging. Immunogenic cell death (ICD) is a type of programmed cell death that is strongly related to the immune system. However, its function in GC requires further investigation.MethodWe used multi‐omics and multi‐angle approaches to comprehensively explore the prognostic features of ICD in patients with stomach adenocarcinoma (STAD). At the single‐cell level, we screened genes associated with ICD at the transcriptome level, selected prognostic genes related to ICD using weighted gene co‐expression network analysis (WGCNA) and machine learning, and constructed a prognostic model. In addition, we constructed nomograms that incorporated pertinent clinical features and provided effective tools for prognostic prediction in clinical settings. We also investigated the sensitivity of the risk subgroups to both immunotherapy and drugs. Finally, in addition to quantitative real‐time polymerase chain reaction, immunofluorescence was used to validate the expression of ICD‐linked genes.ResultsBased on single‐cell and transcriptome WGCNA analyses, we identified 34 ICD‐related genes, of which 11 were related to prognosis. We established a prognostic model using the least absolute shrinkage and selection operator (LASSO) algorithm and identified dissimilarities in overall survival (OS) and progression‐free survival (PFS) in risk subgroups. The nomograms associated with the ICD‐related signature (ICDRS) demonstrated a good predictive value for clinical applications. Moreover, we detected changes in the tumor microenvironment (TME), including biological functions, mutation landscapes, and immune cell infiltration, between the high‐ and low‐risk groups.ConclusionWe constructed an ICD‐related prognostic model that incorporated features related to cell death. This model can serve as a useful tool for predicting the prognosis of GC, targeted prevention, and personalized medicine.

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Definition of a Novel Immunogenic Cell Death-Relevant Gene Signature Associated with Immune Landscape in Gastric Cancer

Cited by 5 publications

References 60 publications

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis

Immunogenic cell death–related genes predict prognosis and response to immunotherapy in lung squamous cell carcinoma

Unraveling the immunogenic cell death pathways in gastric adenocarcinoma: A multi‐omics study

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