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Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study.

ABSTRACT: Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log2 fold change (log2FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as log2FC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of PCK1 and decreased expression of FCGR1A. Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. Log2FCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts.

SUBMITTER: Cho O

PROVIDER: S-EPMC8153571 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study.

Cho Oyeon O Kim Do-Wan DW Cheong Jae-Youn JY

Journal of clinical medicine 20210513 10

Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log<sub>2</sub> fold change (log<sub>2</sub>FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cance ...[more]

PMID: 34068397

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Project description:BackgroundExcess weight and metabolic disorders have a negative impact on male reproductive functions. The mechanisms involved are numerous and complex and epigenetic mechanisms may also be involved, notably through the small non-coding RNAs. Among them, microRNAs (miRNAs) are of particular interest. This preliminary study aimed to identify the miRNAs differentially enriched in seminal plasma related to metabolic disorders and if some are also associated with spermatic parameters alterations. One hundred and sixty men between 18 to 45 years, partners of infertile couple, were included in this cohort. The miRNAs associated with metabolism were selected from the literature and assayed by quantitative real-time PCR using TaqMan gene expression assays. A subset of those with an interesting profile in seminal plasma were secondarily tested in blood.ResultsAmong the 11 selected miRNAs, seven were detected in seminal plasma (miR10b, miR19a, miR19b, miR34b, miR34c, miR133b, miRlet7c). A negative correlation was observed between seminal miR19a levels and metabolic syndrome, blood glucose and C-peptide. Seminal miR19b levels were also negatively correlated with metabolic syndrome. Seminal miR34c levels were negatively correlated with body mass index (BMI) and waist circumference. Seminal miR133b levels were positively correlated with BMI, waist circumference and leptin levels. Interestingly, modifications of miRNAs in seminal plasma seem specific since highlighted above correlations were not retrieved in the blood plasma for the miR19a, 19b, 10b, 34c.ConclusionFew metabolic and anthropometric disorders are correlated with the level of specific miRNAs in seminal plasma. Further studies will be required to decipher if other small non-coding RNAs may also be correlated with metabolic and anthropometric disorders and to assess their potential implication in the alteration of reproductive functions in men with obesity or metabolic disorders.Clinical studyMetabolic Syndrome and Male Infertility (Metasperme): Trial registration: NCT01974947 . Registered 18 July 2013.

Project description:BackgroundPelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied.ObjectiveTo examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy.Materials and methodsThis is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n = 729) or in combination with concurrent chemo-radiotherapy (n = 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection.ResultsAmong 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P = .052), followed by a more gradual rise through 2016 (88.3%, P < .001). In a multivariable model, women with non-squamous cell carcinomas and those diagnosed more recently were more likely to receive concurrent chemo-radiotherapy, whereas older women were less likely to receive concurrent chemo-radiotherapy (all, P < .05). At the population level, the 5-year overall survival rates remained unchanged (annual percent change for 1997-2012: -0.1; 95% confidence interval, -1.2 to 1.0; P = .776). In a propensity score weighted cohort, women who received concurrent chemo-radiotherapy had a 5-year overall survival rate similar to women treated with radiotherapy alone (73.1% vs 73.6%; hazard ratio, 1.004; 95% confidence interval, 0.887-1.136; P = .955). Significant differences were also not seen in older women, nonsquamous types, stage T2 disease, and multiple node metastases (all, P > .05).ConclusionDespite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodal metastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.

Dataset Information

Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study.

Publications

Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study.

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