Plasma-Derived Exosomal microRNA-130a Serves as a Noninvasive Biomarker for Diagnosis and Prognosis of Oral Squamous Cell Carcinoma

He, Tao; Guo, Xiangyu; Li, Xue; Liao, Chunjuan; Wang, Xiaorong; He, Kai

doi:10.1155/2021/5547911

Cited by 33 publications

(23 citation statements)

References 37 publications

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“…Previous studies showed that the composition and cargo of TEX correlates with disease stage, tumor activity and progression, assigning them great potential as biomarkers for HNSCC (11,(17)(18)(19)(20). Additionally, exosomal miRNAs from plasma or serum show promising disease-discriminatory potential in oral (21) and laryngeal cancer (22).…”

Section: Introductionmentioning

confidence: 99%

Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer

Hofmann¹,

Medyany²,

Ezić³

et al. 2022

Front. Med.

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BackgroundExosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the cargo and functional profile of saliva-derived exosomes from HNSCC patients and their potential as non-invasive biomarkers for disease detection and immunomodulation.MethodsExosomes were isolated from saliva of HNSCC patients (n = 21) and healthy donors (HD, n = 12) by differential ultracentrifugation. Surface values of immune checkpoints and tumor associated antigens on saliva-derived exosomes were analyzed by bead-based flow cytometry using CD63 capture. Upon co-incubation with saliva-derived exosomes, activity and proliferation of T cells were assessed by flow cytometry (CD69 expression, CFSE assay). Adenosine levels were measured by mass spectrometry after incubation of saliva-derived exosomes with exogenous ATP. miRNA profiling of saliva-derived exosomes was performed using the nCounter® SPRINT system.ResultsSaliva-derived, CD63-captured exosomes from HNSCC patients carried high amounts of CD44v3, PDL1 and CD39. Compared to plasma, saliva was rich in tumor-derived, CD44v3+ exosomes and poor in hematopoietic cell-derived, CD45+ exosomes. CD8+ T cell activity was attenuated by saliva-derived exosomes from HNSCC patients, while proliferation of CD4+ T cells was not affected. Further, saliva-derived exosomes produced high levels of immunosuppressive adenosine. 62 HD- and 31 HNSCC-exclusive miRNAs were identified. Samples were grouped in “Healthy” and “Cancer” based on their saliva-derived exosomal miRNA profile, which was further found to be involved in RAS/MAPK, NF-κB complex, Smad2/3, and IFN-α signaling.ConclusionsSaliva-derived exosomes from HNSCC patients were enriched in tumor-derived exosomes whose cargo and functional profile reflected an immunosuppressive TME. Surface values of CD44v3, PDL1 and CD39 on CD63-captured exosomes, adenosine production and the miRNA cargo of saliva-derived exosomes emerged as discriminators of disease and emphasized their potential as liquid biomarkers specific for HNSCC.

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Section: Introductionmentioning

confidence: 99%

Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer

Hofmann¹,

Medyany²,

Ezić³

et al. 2022

Front. Med.

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“…The influence analysis and outlier detection identified several outlier individual studies. After excluding seven outliers ( 34 , 38 , 41 , 47 , 48 ), the I 2 for heterogeneity decreased both in sensitivity (from 91.49% to 84.30%) and specificity (from 89.17% to 84.31%). However, the overall results showed only minimal changes and were similar to the original ones as the pooled specificity of the overall study increased from 0.76 to 0.78, PLR increased from 3.2 to 3.4, DOR decreased from 9 to 10, and AUC increased from 0.82 to 0.83, while sensitivity and NLR had no changes.…”

Section: Resultsmentioning

confidence: 97%

The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma

et al. 2022

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BackgroundRecent studies have highlighted the biomarker role of circulating miRNAs in oral squamous cell carcinoma (OSCC), indicating their potential application as early diagnostic markers for OSCC. However, the diagnostic results have proven inconclusive. This study was conducted to evaluate the diagnostic value of circulating miRNAs for OSCC diagnosis.MethodsEligible published studies were identified by a literature search carried out in several databases by using combinations of keywords associated with OSCC, circulating miRNAs, and diagnosis. The bivariate meta-analysis model was adopted to summarize the pooled parameters. Afterwards, we thoroughly explored the sources of heterogeneity after evaluating the risk of bias.ResultsA total of 60 studies focusing on 41 circulating miRNAs were included. The pooled sensitivity, specificity, and AUC were 0.75 (95%CI: 0.69-0.80), 0.76 (0.70-0.81), 0.82 (0.79-0.85), respectively. Subgroup analyses showed that miRNA combinations were more accurate than single miRNAs. Additionally, plasma may be a better matrix for miRNAs assays in OSCC diagnosis as the plasma-based miRNA assay had a higher level of diagnostic accuracy than serum-based miRNA assay. Subgroup analyses also suggested that using circulating miRNAs for OSCC diagnosis is more effective in Caucasians than in Asian ethnic groups. Finally, circulating miRNA assays based on large sample sizes have superior diagnostic accuracy than small sample sizes.ConclusionCirculating miRNAs might be applied as effective surrogate biomarkers for early diagnosis of OSCC. Nevertheless, future larger-scale prospective studies should be performed to enhance the diagnostic efficiency and investigate the miRNA combinations with more pronounced accuracy.

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“…The Exo-miR profiling showed a significant increase in Exo-miR-130a-3p in patients with relapse. MiR-130a-3p has mainly been described as down-modulated in lung cancer compared to normal lung tissue [ 32 ], but the Exo associated form has been correlated with an unfavorable prognosis in some cancer types [ 33 , 34 ]. This opposite effect is not surprising; indeed, Exo-miRs, as being circulating, can act not only on tumor cells but on immune and stromal cells as well, modifying their functions in a context-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

A Circulating Risk Score, Based on Combined Expression of Exo-miR-130a-3p and Fibrinopeptide A, as Predictive Biomarker of Relapse in Resectable Non-Small Cell Lung Cancer Patients

Marconi

Croce

Chiorino

et al. 2022

Cancers

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To date, the 5-year overall survival rate of 60% for early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on an interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. In order to identify a prognostic score, we performed in-depth high-throughput analyses of plasma circulating markers, including exosomal microRNAs (Exo-miR) and peptides, in 67 radically resected NSCLCs. The miRnome profile selected the Exo-miR-130a-3p as the most overexpressed in relapsed patients. Peptidome analysis identified four progressively more degraded forms of fibrinopeptide A (FpA), which were depleted in progressing patients. Notably, stepwise Cox regression analysis selected Exo-miR-130a-3p and the greatest FpA (2-16) to build a score predictive of recurrence, where high-risk patients had 18 months of median disease-free survival. Moreover, in vitro transfections showed that higher levels of miR-130a-3p lead to a deregulation of pathways involved in metastasis and angiogenesis, including the coagulation process and metalloprotease increase which might be linked to FpA reduction. In conclusion, by integrating circulating markers, the identified risk score may help clinicians predict early-stage NSCLC patients who are more likely to relapse after primary surgery.

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Plasma-Derived Exosomal microRNA-130a Serves as a Noninvasive Biomarker for Diagnosis and Prognosis of Oral Squamous Cell Carcinoma

Cited by 33 publications

References 37 publications

Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer

Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer

The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma

A Circulating Risk Score, Based on Combined Expression of Exo-miR-130a-3p and Fibrinopeptide A, as Predictive Biomarker of Relapse in Resectable Non-Small Cell Lung Cancer Patients

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