Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies

El-Tanani, Mohamed; Rabbani, Syed Arman; Babiker, Rasha; Rangraze, Imran; Kapre, Sumedha; Palakurthi, Sushesh Srivastsa; Alnuqaydan, Abdullah M.; Aljabali, Alaa A.; Rizzo, Manfredi; El-Tanani, Yahia; Tambuwala, Murtaza M.

doi:10.1016/j.canlet.2024.216894

Cited by 14 publications

(1 citation statement)

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“…Mitochondria, as cell organelles with diverse biological functions and high plasticity, play a crucial role in regulating metabolism and activating immune cells ( 30 , 31 ). Studies have shown that mitochondrial dysfunction in various cells within the tumor microenvironment, including tumor cells and immune cells, is a significant factor in the occurrence, development, and metastasis of cancer ( 32 ). Therefore, starting from the role of mitochondrial energy metabolism in regulating tumor immunity, we screened genes associated with the prognosis of cervical cancer patients and constructed a risk score for prognosis.…”

Section: Discussionmentioning

confidence: 99%

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes

Ma,

Ren,

Yin

et al. 2024

Front. Immunol.

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BackgroundCervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women’s lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism.MethodsTranscriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively.ResultsA prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors.ConclusionThe aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients’ prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%