Circulating exosomal miRNAs: clinical significance in human cancers

Avgeris, Margaritis; Panoutsopoulou, Konstantina; Papadimitriou, M.; Scorilas, Andreas

doi:10.1080/14737159.2019.1673732

Cited by 29 publications

(20 citation statements)

References 169 publications

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“…Breast cancer is an extremely common malignancy in women and has a poor prognosis. In recent years, new biomarkers have emerged for the prognosis of cancer patients [ 17 ], but this is the first time to discuss the establishment of a prognostic model related to ferroptosis in breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Wang

Wei

et al. 2021

BMC Cancer

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Background Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women’s health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients’ survival. Methods Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score. Results We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001). Conclusion Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients’ prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Wang

Wei

et al. 2021

BMC Cancer

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“…Exosomal microRNAs have a key role in the tumor microenvironment of breast cancer and may serve as molecular markers [36]. Their analytical stability constitutes exosomal miRNAs as promising molecular markers to overcome numerous limitations of cancer clinical management [37].…”

Section: Composition Of Cancer Exosomesmentioning

confidence: 99%

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

Olejarz

Dominiak

Żołnierzak

et al. 2020

Journal of Immunology Research

104

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Tumor-derived exosomes (TEX) are involved in cancer development, metastasis, and disease progression. They can modulate angiogenesis to elevate the malignant degree of tumor cells. TEX carry immunosuppressive factors affecting the antitumor activities of immune cells. Tumor cells as well as immune cells secrete immunologically active exosomes which affect intercellular communication, antigen presentation, activation of immune cells, and immune surveillance. Cell proliferation and immune response suppression create a favorable microenvironment for tumor. TEX can inhibit immune cell proliferation, induce apoptosis of activated CD8+ Teffs, suppress NK cell activity, interfere with monocyte differentiation, and promote Treg as well as MDSC expansion. Exosomes of microenvironment cells may also contribute to the development of drug resistance in cancer therapy. An important role of TEX in modulating the sensitivity of tumor cells to immunotherapy is a promising area of research to make the cancer therapy more successful.

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“…Nearly 70% of the human genome encodes for ncRNAs [38], which have been implicated in gene expression regulation at transcriptional, post-transcriptional as well as epigenetic levels, and thus in both health and disease physiology [39,40]. Until recently, miRNAs and lncRNAs had gained most attention for their function and clinical significance in human cancers [41][42][43]. Improvements in high-throughput sequencing and bioinformatic analysis have revealed tRFs as a new class of abundant small ncRNAs derived from tRNAs [17].…”

Section: Discussionmentioning

confidence: 99%

tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5′-tRF-LysCTT Results in Disease Early Progression and Patients’ Poor Treatment Outcome

Papadimitriou

Avgeris

Levis

et al. 2020

Cancers

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The heterogeneity of bladder cancer (BlCa) prognosis and treatment outcome requires the elucidation of tumors’ molecular background towards personalized patients’ management. tRNA-derived fragments (tRFs), although originally considered as degradation debris, represent a novel class of powerful regulatory non-coding RNAs. In silico analysis of the TCGA-BLCA project highlighted 5′-tRF-LysCTT to be significantly deregulated in bladder tumors, and 5′-tRF-LysCTT levels were further quantified in our screening cohort of 230 BlCa patients. Recurrence and progression for non-muscle invasive (NMIBC) patients, as well as progression and patient’s death for muscle-invasive (MIBC) patients, were used as clinical endpoint events. TCGA-BLCA were used as validation cohort. Bootstrap analysis was performed for internal validation and the clinical net benefit of 5′-tRF-LysCTT on disease prognosis was assessed by decision curve analysis. Elevated 5′-tRF-LysCTT was associated with unfavorable disease features, and significant higher risk for early progression (multivariate Cox: HR = 2.368; p = 0.033) and poor survival (multivariate Cox: HR = 2.151; p = 0.032) of NMIBC and MIBC patients, respectively. Multivariate models integrating 5′-tRF-LysCTT with disease established markers resulted in superior risk-stratification specificity and positive prediction of patients’ progression. In conclusion, increased 5′-tRF-LysCTT levels were strongly associated with adverse disease outcome and improved BlCa patients’ prognostication.

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Circulating exosomal miRNAs: clinical significance in human cancers

Cited by 29 publications

References 169 publications

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

tRNA-Derived Fragments (tRFs) in Bladder Cancer: Increased 5′-tRF-LysCTT Results in Disease Early Progression and Patients’ Poor Treatment Outcome

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