Bosnian Journal of Basic Medical Sciences (BJBMS)
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Systemic analysis of the expression and prognostic significance of USP31 in endometrial cancer
Get PDFIncreasing evidence indicates that multiple mechanisms are involved in the metastasis and postoperative recurrence in patients with endometrial cancer (EC). Ubiquitin-specific protease 31 (USP31) has been studied in some human tumors, but its function remains unclear in EC. In this study, we tried to investigate the expression of USP31 in EC and its possible involvement in biological signaling pathways and define its predictive value for the prognosis. Data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases confirmed the difference in USP31 expression between EC and normal endometrium. Specimens and clinical data of 259 patients with EC who underwent primary surgery at the First Affiliated Hospital of Chongqing Medical University were collected. The independent predictive value of USP31 for the prognosis of EC patients was determined by univariate and multivariate analyses. Kaplan-Meier analysis and receiver operating characteristic curves were used for confirming the ability of USP31 to predict the prognosis. Functional enrichment analyses were used for finding the hub genes associated with USP31 and to predict the biological signaling pathways that might be involved. Our study confirms that EC patients with low expression of USP31 may have a worse prognosis. Functional annotations suggest that USP31 may participate in the mitogen-activated protein kinase signaling pathway, nuclear factor κB pathway, early 2 factor targets, and inflammatory response. USP31 may act as a promising biomarker for research in EC
Machine learning for predicting the survival in osteosarcoma patients: Analysis based on American and Hebei Province cohort
Get PDFOsteosarcoma, a rare malignant tumor, has a poor prognosis. This study aimed to find the best prognostic model for osteosarcoma. There were 2912 patients included from the SEER database and 225 patients from Hebei Province. Patients from the SEER database (2008-2015) were included in the development dataset. Patients from the SEER database (2004-2007) and Hebei Province cohort were included in the external test datasets. The Cox model and three tree-based machine learning algorithms (survival tree [ST], random survival forest [RSF] and gradient boosting machine [GBM]) were used to develop the prognostic models by 10-fold cross-validation with 200 iterations. Additionally, performance of models in the multivariable group was compared with the TNM group. The 3-year and 5-year cancer specific survival (CSS) were 72.71% and 65.92% in the development dataset, respectively. The predictive ability in the multivariable group was superior to that in the TNM group. The calibration curves and consistency in the multivariable group were superior to those in the TNM group. The Cox and RSF models performed better than the ST and GBM models. A nomogram was constructed to predict the 3-year and 5-year CSS of osteosarcoma patients. The RSF model can be used as a nonparametric alternative to the Cox model. The constructed nomogram based on the Cox model can provide reference for clinicians to formulate specific therapeutic decisions both in America and China
CSRP2 transcript levels after consolidation therapy increase prognostic prediction ability in B-cell acute lymphoblastic leukaemia
Get PDFQuantification of measurable residual disease (MRD) correlates with the risk of leukemia recurrence in adults with B-cell acute lymphoblastic leukemia (ALL). However, it remains unknown whether collecting data on cysteine and glycine-rich protein 2 (CSRP2) transcript levels, after completing the second course of consolidation, improves prognosis prediction accuracy. A total of 204 subjects with B-cell ALL were tested for CSPR2 transcripts after completing the second course of consolidation using quantitative real-time polymerase chain reaction (qRT-PCR) and divided into high (N = 32) and low (N = 172) CSRP2 expression cohorts. In multivariable analyses, subjects with high expression of CSRP2 had a higher 5-year cumulative incidence of relapse (CIR) (hazard ratio [HR] = 2.57, 95% confidence interval [CI] 1.38-4.76; P = 0.003), lower 5-year relapse-free survival (RFS) (HR = 3.22, 95% CI 1.75-5.93; P < 0.001), and overall survival (OS) (HR = 4.59, 95% CI 2.64-7.99; P < 0.001) in the whole cohort, as well as in the multi-parameter flow cytometry (MPFC) MRD-negative cohort (for CIR, HR = 2.70, 95% CI 1.19-6.12; for RFS, HR = 4.37, 95% CI 1.94-9.85; for OS, HR = 4.90, 95% CI 2.43-9.90; all P < 0.05). Prognostic analysis showed that allogeneic hematopoietic stem cell transplantation (allo-HSCT) could significantly improve the prognosis of patients with high CSRP2 expression (allo-HSCT vs chemotherapy: 5-year CIR, 52% vs 91%; RFS, 41% vs 9%; OS, 38% vs 20%; all P < 0.05). Our data indicate that incorporating data from CSPR2 transcript levels to the MRD-testing at the end of the second course of consolidation therapy enhances prognosis prediction accuracy in adults with B-cell ALL
Exploring the clinical characteristics and etiological factors of comorbid major depressive disorder and social anxiety disorder
Get PDFThe comorbidity between the major depressive disorder (MDD) and the social anxiety disorder (SAD) is significantly prevalent, necessitating a nuanced understanding of their overlapping clinical characteristics and shared etiological factors, including inflammatory biomarkers. To address this, we conducted a cross-sectional study from December 2021 to June 2022, encompassing 204 outpatients diagnosed with MDD-SAD comorbidity. We employed various psychometric assessments, such as the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Childhood Trauma Questionnaire (CTQ-28), Toronto Alexithymia Scale (TAS-20) and the Liebowitz Social Anxiety Scale (LSAS). Additionally, we analyzed inflammatory biomarkers including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte platelet ratio (NLPR), systemic inflammation index (SII), and the systemic inflammation response index (SIRI). Our findings accentuated that patients primarily diagnosed with MDD exhibited elevated levels of certain inflammatory biomarkers. They reported more severe and atypical depressive symptoms (75.7% vs 58.5%; P = 0.010) and had significantly higher CTQ-28 subscale scores (P < 0.05). Our study unveils a complex relationship between MDD and SAD, with significant disparities in the symptom severity and inflammatory biomarker levels, thereby establishing a compelling case for dual-diagnosis treatment approaches. It elucidates the critical role of inflammation in the comorbidity of MDD and SAD, marking a pioneering step towards more comprehensive and holistic patient care strategies. These insights could potentially revolutionize therapeutic approaches in psychiatric care, promising significantly improved outcomes through early detection and integrated intervention strategies
Oral microbiome-driven virulence factors: A novel approach to pancreatic cancer diagnosis
Get PDFPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, often associated with a poor prognosis for patients. One of the major challenges in managing PDAC is the difficulty in early diagnosis, owing to the limited and invasive nature of current diagnostic methods. Recent studies have identified the oral microbiome as a potential source of non-invasive biomarkers for diseases, including PDAC. In this study, we focused on leveraging the differential expression of virulence factors (VFs) encoded by the oral microbiome to create a diagnostic tool for PDAC. We observed a higher alpha diversity in VF categories among PDAC patients compared to healthy controls. We then identified a panel of VF categories that were significantly upregulated in PDAC patients, these being associated with bacterial adherence, exoenzyme production, and nutritional/metabolic processes. Moreover, Streptococcus-derived VFs were notably enriched in PDAC patients. We developed a diagnostic model using random forest analysis based on the levels of these VFs. The model\u27s diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.88, indicating high accuracy in differentiating PDAC patients from healthy controls. Our findings suggest that VFs encoded by the oral microbiome hold potential as diagnostic tools for PDAC, offering a non-invasive approach that could significantly enhance early detection and prognosis, ultimately leading to improved patient outcomes
The value of routine measurement of serum calcitonin on insufficient, indeterminate, and suspicious thyroid nodule cytology
Get PDFRoutine calcitonin measurement in patients with nodular thyroid disease is rather controversial. The aim of this study was to evaluate the contribution of serum calcitonin measurement in the diagnostic evaluation of thyroid nodules with insufficient, indeterminate, or suspicious cytology. Out of 1668 patients who underwent thyroidectomy with the diagnosis of nodular thyroid disease and were screened, 873 patients with insufficient, indeterminate, or suspicious fine needle aspiration biopsy results were included in the study. From the total number of patients in this study, 10 (1.1%) were diagnosed as medullary thyroid cancer (MTC) using histopathology. The calcitonin level was detected to be above the assay-specific cut-off in 23 (2.6%) patients ranging between 6.5 - 4450 pg/mL. While hypercalcitoninemia was detected in all 10 MTC patients, a false positive elevation of serum calcitonin was detected in 13 patients (1.5%). Of the MTC group, 7 patients had cytology results that were suspicious for malignancy (Bethesda V), one patient’s cytology showed atypia of undetermined significance (Bethesda III) and two patient’s cytology results were suspicious for follicular neoplasm (Bethesda IV). Among the cases with non-diagnostic cytology (Bethesda I), none of the patients were diagnosed with MTC. In conclusion, routine serum calcitonin measurement can be performed in selected cases rather than in all nodular thyroid patients. While it is reasonable to perform routine calcitonin measurement in patients with Bethesda IV and Bethesda V, this measurement was not useful in Bethesda I patients. In Bethesda III patients, patient-based decisions can be made according to their calcitonin measurement.
 
Role of dynamic contrast enhanced magnetic resonance imaging in the diagnosis and management of vascular lesions of the head and neck
Get PDFVascular anomalies comprise a wide and heterogeneous group of lesions that may be found in all parts of the body, with most of the cases of vascular malformations involving the head and neck region. Ultrasound (US) is the reliable first-line imaging technique to assess flow parameters. However, in some cases, US fails to depict the real extent of the lesions. On the other hand, magnetic resonance imaging (MRI) allows the evaluation of the full extension and anatomic relationship of the vascular anomalies with the neighboring structures and provides hemodynamic characterization using dynamic contrast enhanced MRI (DCE-MRI), avoiding unnecessary invasive catheter-based procedures. DCE-MRI angiography can make a distinction between low and high flow vascular anomalies and it is useful for selecting adequate therapy and appreciating prognosis. The aim of this paper is to review the role of DCE -MRI in the evaluation of flow characteristics and lesion extent in vascular anomalies of the head and neck region
Construction and validation of a preterm birth risk assessment model using fuzzy analytic hierarchy process
Get PDFPreterm births account for almost 1 million deaths globally. The objective of this study is to develop and evaluate a model that assists clinicians in assessing the risk of preterm birth, using fuzzy multicriteria analysis. The model allows experts to incorporate their intuition and judgment into the decision-making process and takes into consideration six (6) risk dimensions reflecting the socio-economic, behavioural and medical profile of pregnant women, thus adopting a holistic approach to risk assessment. Each risk dimension is further analysed and measured in terms of risk factors associated with it. Data was collected from a selected group of 35 experts, each one with more than 20 years of obstetric experience. The model criteria were selected after a thorough literature analysis, so as to ensure a holistic approach to risk assessment. The criteria were reviewed by the experts and the model structure was finalised. The fuzzy analytic hierarchy method was applied to calculate the relative importance of each criterion and subsequent use of the model in assessing and ranking pregnant women by their preterm risk. The proposed model utilises fuzzy logic and multicriteria analysis. It addresses the multifactorial nature of decision making when assessing the preterm birth risk. It also incorporates the obstetricians’ intuitive judgement during risk assessment and it can be used to classify cases based upon their risk level. Additionally, it can be applied to evaluate the risk of individual cases in a personalised manner. The proposed model is compared and validated for its predictive value against judgments made by experts. 
Dysregulated circulating miR-4429 serves as a novel non-invasive biomarker and is correlated with EGFR mutation in patients with non-small cell lung cancer
Get PDFThis study aimed to investigate the correlation between microRNA (miR)-4429 and epidermal growth factor receptor (EGFR), the expression and clinical significance of miR-4429 in patients with non-small cell lung cancer (NSCLC), and the relationship between miR-4429 and EGFR mutation in NSCLC patients. Blood samples were collected from 122 NSCLC patients and 72 healthy volunteers. miR-4429 expression and EGFR mRNA expression were detected by real-time quantitative PCR. Correlation between miR-4429 and EGFR was evaluated by dual‑luciferase reporter assay and the Pearson correlation analysis. The ability of serum miR‑4429 to discriminate between NSCLC patients and healthy controls, and to discriminate between EGFR wild-type (EGFR-W) and EGFR mutant-type (EGFR-M) patients was assessed using receiver operating characteristic analysis. The relationship between miR-4429 and NSCLC patients’ survival was identified by Kaplan-Meier survival curves and log-rank test. The prognostic value of miR-4429 in NSCLC patients was evaluated by Cox regression analysis. miR-4429 could directly bind to EGFR. Serum miR-4429, decreased in NSCLC patients, was negatively correlated with serum EGFR mRNA expression in NSCLC patients. Additionally, miR-4429 had a high diagnostic value for screening NSCLC patients from healthy controls, and was independently correlated with survival prognosis of NSCLC patients. Moreover, miR‑4429 was decreased in EGFR-M patients, which had a certain screening ability for EGFR‑M patients. Our findings indicate that miR-4429 is negatively correlated with EGFR in NSCLC, and may function as a diagnostic and prognostic biomarker for NSCLC patients. Additionally, miR-4429 is associated with EGFR mutation in NSCLC patients
Identification and verification of the ferroptosis- and pyroptosis-associated prognostic signature for low-grade glioma
Get PDFAccumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes and further identify and verify a novel multigene signature in LGG on the basis of ferroptosis and pyroptosis-related genes (FPRGs). Raw sequencing data and corresponding clinical data of LGG samples retrieved from the TCGA and CGGA databases were obtained for the training and validation datasets. Non-negative matrix factorization (NMF) clustering defined by FPRGs associated with prognosis was performed to classify molecular subtypes of LGG patients. LASSO-SVM-Random Forest analysis was carried out to develop an FPRG signature to predict the survival and benefit of immunotherapy of LGG patients. NMF clustering defined by FPRGs with prognostic values acted to categorize LGG patients into two molecular subtypes with different prognosis, clinical traits and immune microenvironments. A six-FPRG prognostic signature was constructed, accompanied by the optimal p-value. The AUC values of our signature exhibited great prognostic performances. Our signature was superior to other four well-recognized signatures in predicting the survival probability of LGG patients. Immune characteristics, tumor mutation profile, tumor stemness indices, MGMT methylation and immunotherapy response biomarkers showed significant differences between high- and low-risk populations. Finally, a nomogram was created for quantitative prediction of the survival probability of LGG patients, with the AUC values of the nomogram being 0.916, 0.888 and 0.836 for 1-, 3- and 5-year survival, sequentially. Overall, the FPRG signature may function as an effective indicator for the prognosis prediction and immunotherapy response of LGG patients