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Plasmatic Exosome Number and Size Distinguish Prostate Cancer Patients From Healthy Individuals: A Prospective Clinical Study

ABSTRACT: There is a urgent need for valuable strategy in early and less invasive diagnosis for cancer. Preliminary data have shown that the plasmatic levels of exosomes increase in cancer condition. This study investigates the relevance of plasmatic levels and size distribution of exosomes in 42 individuals with no signs of urological disease (CTR) as compared to 65 prostate cancer patients (PCa). It was used Nanoparticle Tracking Analysis (NTA), a highly reliable and sensitive method for exosomes characterization and quantification. The relation structure among the NTA-derived parameters was assessed by means of Principal Component Analysis, which allowed detecting the global discriminant power of NTA test in terms of Receiver Operating Characteristic (ROC) curve and the selection of cut-off thresholds. The results showed that PCa had significantly higher plasmatic levels of exosomes and that the exosomes were smaller in size as compared to the CTR; the values reached 89% sensitivity and 71% specificity, in distinguishing PCa from CTR. These results propose a new exosome-based non-invasive clinical approach for the clinical follow-up of prostate cancer undergoing surgical treatment; in addition this method may be developed as a new screening test for prostate cancer’s early diagnosis. While this clinical study was performed in prostate cancer, it may represent a proof of concept extendable to virtually all cancers, as it is suggested by both pre-clinical evidence and clinical data obtained with different technical approaches.

SUBMITTER: Logozzi M

PROVIDER: S-EPMC8564386 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale. Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not completely uncovered. Objectives. We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and nonobese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and COX-2, a pro-angiogenic pathway. Methods and Results. MPs were obtained from thrombin activated platelets of four obese women and their matched, lean controls . MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. Obese MPs were not different in number but were characterized by increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and 3 upregulated in obese versus nonobese MPs . A reduction in the proteins involved in mitophagy and antioxidant defenses, and of the -granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with HT29 cells and human cardiac microvascular endothelial cells(HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. MPs from obese, but not nonobese, women induced COX-2 in HCMEC. Conclusions. Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. Obese MPs presented enhanced capacity to induce changes in the expression of EMT and EndMT markers and COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity.

Project description:Importance:An aging population experiences an increase in age-related problems, such as presbyphonia. The causes of pathologic presbyphonia are incompletely understood. Objective:To determine what distinguishes pathologic presbyphonia from presbylaryngis. Design, Setting, and Participants:This was a cohort study at an outpatient otolaryngology subspecialty clinic of a tertiary academic referral center. Participants were consecutive consenting adults older than 74 years without laryngeal pathologic abnormalities who visited the clinic as participants or companions. Patient questionnaires, otolaryngologic, video stroboscopic, and voice examinations were compiled. Patients were divided into groups based on whether they endorsed a voice complaint. Three blinded authors graded stroboscopic examinations for findings consistent with presbylaryngis (vocal fold bowing, vocal process prominence, glottic insufficiency). Main Outcomes and Measures:Voice Handicap Index-10, Reflux Symptom Index, Cough Severity Index, Dyspnea Index, Singing Voice Handicap Index-10 , Eating Assessment Tool -10, Voice-Related Quality of Life (VRQOL), and Short-Form Health Survey; face-sheet addressing social situation, work, marital status, education, voice use, transportation; acoustic and aerodynamic measures; and a full otolaryngologic examination, including videostroboscopic imaging. Results:A total of 31 participants with dysphonia (21 were female; their mean age was 83 years [range, 75-97 years]) and 26 control participants (16 were female; their mean age was 81 years [range, 75-103 years]) completed the study. Presbylaryngis was visible in 27 patients with dysphonia (87%) and 22 controls (85%). VHI-10 and VRQOL scores were worse in patients with pathologic presbyphonia (median [range] VHI-10 scores, 15 (0-40) vs 0 (0-16) and median VRQOL score, 19 [0-43] vs 10 [10-23]). All other survey results were indistinguishable, and no social differences were elucidated. Acoustic measures revealed that both groups averaged lower than normal speaking fundamental frequency (mean [SD], 150.01 [36.23] vs 150.85 [38.00]). Jitter was 3.44% (95% CI, 2.46%-4.61%) for pathologic presbyphonia and 1.74% (95% CI, 1.35%-2.14%) for controls (d = 0.75). Shimmer means (95% CI) were 7.8 2 (6.08-10.06) for the pathologic presbyphonia group and 4.84 (3.94-5.72) for controls (d = 0.69). Aerodynamic measures revealed an odds ratio of 3.03 (95% CI, 0.83-11.04) for patients with a maximum phonation time of less than 12 seconds who had complaints about dysphonia. Conclusions and Relevance:Presbylaryngis is present in most ambulatory people older than 74 years. Some will endorse pathologic presbyphonia that has a negative effect on their voice and quality of life. Pathologic presbyphonia seems to be influenced by respiratory capacity and sex. Further study is required to isolate other social, physiologic, and general health characteristics that contribute to pathologic presbyphonia.

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Plasmatic Exosome Number and Size Distinguish Prostate Cancer Patients From Healthy Individuals: A Prospective Clinical Study

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