Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and it can be locally invasive and metastatic to distant sites. MicroRNAs (miRNAs or miRs) are endogenous, small, non-coding RNAs of 19–25 nucleotides in length, that are involved in regulating gene expression at a post-transcriptional level. MicroRNAs have been implicated in diverse biological functions and diseases. In cancer, miRNAs can proceed either as oncogenic miRNAs (onco-miRs) or as tumor suppressor miRNAs (oncosuppressor-miRs), depending on the pathway in which they are involved. Dysregulation of miRNA expression has been shown in most of the tumors evaluated. MiRNA dysregulation is known to be involved in the development of cutaneous squamous cell carcinoma (CSCC). In this review, we focus on the recent evidence about the role of miRNAs in the development of CSCC and in the prognosis of this form of skin cancer.

/pdf/microrna-dysregulation-in-cutaneous-squamous-cell-carcinoma-4llzzp8h1c.pdf

MicroRNA Dysregulation in Cutaneous Squamous Cell Carcinoma

Breast cancer (BC) is the most frequent malignant disease in women worldwide and is therefore challenging for the healthcare system. Early BC detection remains a leading factor that improves overall outcome and disease management. Aside from established screening procedures, there is a constant demand for additional BC detection methods. Routine BC screening via non-invasive liquid biopsy biomarkers is one auspicious approach to either complete or even replace the current state-of-the-art diagnostics. The study explores the diagnostic potential of urinary exosomal microRNAs with specific BC biomarker characteristics to initiate the potential prospective application of non-invasive BC screening as routine practice. Based on a case–control study (69 BC vs. 40 healthy controls), expression level quantification and subsequent biostatistical computation of 13 urine-derived microRNAs were performed to evaluate their diagnostic relevance in BC. Multilateral statistical assessment determined and repeatedly confirmed a specific panel of four urinary microRNA types (miR-424, miR-423, miR-660, and let7-i) as a highly specific combinatory biomarker tool discriminating BC patients from healthy controls, with 98.6% sensitivity and 100% specificity. Urine-based BC diagnosis may be achieved through the analysis of distinct microRNA panels with proven biomarker abilities. Subject to further validation, the implementation of urinary BC detection in routine screening offers a promising non-invasive alternative in women’s healthcare.

Urinary Exosomal MicroRNAs as Potential Non-invasive Biomarkers in Breast Cancer Detection

On cancer diagnostic

Tissue biopsy is the gold standard for diagnosis and morphological and immunohistochemical analyses to characterize cancer. However, tissue biopsy usually requires an invasive procedure, and it can be challenging depending on the condition of the patient and the location of the tumor. Even liquid biopsy analysis of body fluids such as blood, saliva, gastric juice, sweat, tears and cerebrospinal fluid may require invasive procedures to obtain samples. Liquid biopsy can be applied to circulating tumor cells (CTCs) or nucleic acids (NAs) in blood. Recently, urine has gained popularity due to its less invasive sampling, ability to easily repeat samples, and ability to follow tumor evolution in real-time, making it a powerful tool for diagnosis and treatment monitoring in cancer patients. With the development and advancements in extraction methods of urinary substances, urinary NAs have been found to be closely related to carcinogenesis, metastasis, and therapeutic response, not only in urological cancers but also in non-urological cancers. This review mainly highlights the components of urine liquid biopsy and their utility and limitations in oncology, especially in non-urological cancers.

Urine as a Source of Liquid Biopsy for Cancer

Prostate cancer is a global biological, medical, and social issue aggravated by the lack of reliable, highly specific, and sensitive non-invasive tests for diagnosis and staging of prostate cancer. One prospective source of biomarkers are the cell-free miRNAs present in various biological fluids. In the present study, we validated the diagnostic potential of cell-free miRNAs: miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, and miR-660; we estimated the required sample size and the minimal miRNA set for a subsequent large-scale validation study. Relative expression of 12 miRNA combined in 31 ratios was investigated in three fractions of biological fluids (urine extracellular vesicles, clarified urine, and plasma) obtained from patients with prostate cancer (n = 10), benign prostate hyperplasia (n = 8), and healthy volunteers (n = 11). Eight of the miRNAs found in urine vesicles (miR-19b, miR-30e, miR-31, miR-92a, miR-125, miR-200, miR-205, and miR-660) showed great promise and when combined into six ratios (miR-125b/miR-30e, miR-200/miR-30e, miR-205/miR-30e, miR-31/miR-30e, miR-660/miR-30e, and miR-19b/miR-92a) could classify patients with prostate cancer, benign prostate hyperplasia, and healthy donors with 100% specificity, 100% sensitivity, and with a high degree of reliability for most donors.

https://www.mdpi.com/2075-4418/10/1/38/pdf

The Panel of 12 Cell-Free MicroRNAs as Potential Biomarkers in Prostate Neoplasms.

The aim of this study was to investigate miRNA profiles of clarified urine supernatant and combined urine vesicle fractions of healthy donors and patients with benign prostatic hyperplasia and prostate cancer (PCa). The comparative analysis of miRNA expression was conducted with a custom miRCURY LNA miRNA qPCR panel. Significant combinations of miRNA pairs were selected by the RandomForest-based feature selection algorithm Boruta; the difference of the medians between the groups and a 95% confidence interval was built using the bootstrap approach. The Asymptotic Wilcoxon-Mann-Whitney Test was performed for miRNA combinations to compare different groups of donors. Benjamini-Hochberg correction was used to adjust the statistical significance for multiple comparisons. The most diagnostically significant miRNAs pairs were miR-107-miR-26b.5p and miR-375.3p-miR-26b.5p in the urine supernatant fraction that discriminated the group of healthy patients and PCa patients, as well as miR-31.5p-miR-16.5p, miR-31.5p-miR-200b, miR-31.5p-miR-30e.3p and miR-31.5p-miR-660.5p in the fraction extracellular vesicles that were different between healthy men and benign prostate hyperplasia patients. Such statistical criteria as the occurrence of individual significant miRNA pairs in the total number of comparisons, median ΔCt difference, and confidence interval can be useful tools for determining reliable markers of PCa.

https://www.mdpi.com/1422-0067/19/12/4088/pdf

Searching for the Novel Specific Predictors of Prostate Cancer in Urine: The Analysis of 84 miRNA Expression.

Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy.

/pdf/data-analysis-algorithm-for-the-development-of-extracellular-3tqfuni5rh.pdf

Data analysis algorithm for the development of extracellular miRNA-based diagnostic systems for prostate cancer.

MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e., miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375 and miR-660). The relative expression of the miRNAs combined into 31 paired ratios was evaluated in the urine extracellular vesicles (EVs), clarified urine (CU) and blood plasma of healthy donors, pre- and post-RP samples of PCa patients. Nineteen miRNA ratios based on combinations of ten of the miRNAs (miR-19b, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, miR-378, miR-425, and miR-660) were altered by RP. The comparative expression analysis of the cell-free miRNA ratios between healthy donors and PCa patients revealed miR-125b/miR-30e and miR-375/miR-30e as potential markers for evaluating therapeutic efficacy. MiR-378/miR-19b, miR-425/miR-19b, miR-200/miR-30e, miR-660/miR-30e, and miR-205/miR-30e had minor prognostic value but could be used to increase the steadiness of the diagnostic system. The urine EVs had the highest potential as a source of markers.

https://www.mdpi.com/2075-4418/10/8/600/pdf

The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA.

Introduction 
Incidence of adult degenerative scoliosis (ADS) among individuals over 50 years old reaches 68%. Surgical interventions aimed at correcting the spinal deformity in patients of the older age group are accompanied by a high risk of complications. The use of LLIF is associated with lower complications as compared with open anterior or posterior fusion. 
Materials and methods 
Seventy-one patients with ADS (13 men, 58 women) were operated at the Federal Neurosurgical Center. Their average age was 60.4/60 (average/median) [55;64.5] (1: 3 quartile) years. The follow-up was from 12 to 18 months. X-ray study, SCT, MRI of the lumbar spine were used. Questionnaire surveys were conducted using the visual analog pain scale (VAS), Oswestry Disability Index (ODI) and the Short Form-36 (SF-36). Deformity correction was estimated in the frontal plane with Cobb’s method. Scoliosis was classified according to SRS-Schwab classification. Parameters of sagittal balance were estimated: PI (Pelvic incidence), SS (Sacral slope), PT (Pelvic tilt), LL (Lumbar lordosis). SVA, PT and PILL (PI minus LL) were defined adjusted for the age. 
Results 
Back pain according to VAS relieved from 6.1/6 [4;8] to 2.2/2 [2;3] points (p less 0.001) and was statistically significant at 12 months after the surgery. Leg pain according to VAS decreased from 5.4/5 [4;8] to 2.1/2 [1;3] points (p less 0.001) and was statistically significant at 12 months after the surgery. Functional adaptation according to ODI improved from 51.2/52.2 [38.6;64.1] to 31.8/33.3 [26.1;35.9] (p less 0.001). According to SF36, PH before the surgery was 25.7/24.3 [21.8;28.9] on average and at 12 months after the surgery - 38.7/38.7 [35.4;41.2] (p less 0.001). SF-36 MH before surgery was 27.1/26.3 [21.8;31.4] on average and 12 months later – 41.3/40.6 [36.5;43.7] (p less 0.001). PT before the surgery was 23.3/22° [17.5;28], 12 months later it was 17.9/17° [15;20] (p less 0.001). PI-LL was 11.5/10 ° [4;17.5], 12 months later – 8.4/8 ° [5.5;11.5] (p = 0.11). Transient paresis of femur flexors on the ipsilateral side was observed in five (7 %) cases; transient hyposthesia on the anterior thigh surface occurred in eight (11.2 %) cases. There were two cases of medial malposition (0.4 %) of pedicle screws (474 screws), pseudoarthrosis at two levels (1.2 %) (Grade 4 Bridwell) out of 166 levels performed, and seven (4.2 %) cases of damage to cortical endplates. 
Conclusion 
Restoration of local sagittal balance in ADS patients by short-segment fixation using LLIF technology leads to a statistically significant improvement in the quality of life and increases functional adaptation. Few early and late postoperative complications, less intraoperative blood loss and shorter hospital stay make LLIF in combination with MIS transpedicular fixation a method of choice in determining the surgical tactics for ADS in elderly and old age patients.

/pdf/the-use-of-llif-technology-in-adult-patients-with-dp0rjw4uzg.pdf

E. V. Amelina

Papers

Searching for the Novel Specific Predictors of Prostate Cancer in Urine: The Analysis of 84 miRNA Expression.

Data analysis algorithm for the development of extracellular miRNA-based diagnostic systems for prostate cancer.

The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA.

The use of LLIF technology in adult patients with degenerative scoliosis: retrospective cohort analysis and literature review

Determining the law of ice deformation