Prognosis Value Research Articles

CSPG4 overexpression implicates higher risks of recurrence and tumorigenesis after surgical intervention of vocal fold Leukoplakia.

Vocal fold leukoplakia (VFL), a precancerous lesion of the larynx, is characterized by white plaques on the vocal fold mucous membrane. Currently, there are no reliable biomarkers to predict the recurrence and malignant transformation of VFL. Considering chondroitin sulfate proteoglycan 4 (CSPG4) as a biomarker for malignant tumors such as laryngeal squamous cell carcinoma (LSCC), we conducted this cohort study to evaluate the prognostic influence of CSPG4 expression on VFL patients. This study included 44 patients with surgical intervention of VFL. CSPG4 expression in VFL were observed using immunohistochemistry, and the relationship between the prognosis of VFL patients and CSPG4 expression were investigated using Spearman correlation analysis and multiple Cox regression models. During a median follow-up of 89.3 months, recurrence occurred in 19 postsurgical VFL patients, and malignant transformation occurred in 10 patients. The recurrence and malignant transformation group showed significant differences in the H-SCORE of CSPG4 (P = 0.005 and P = 0.045) compared to the the non-recurrence group and the non-malignant transformation group. And the CSPG4 expression level was positive correlation with recurrence and malignant transformation (0.306 or 0.416, spearman correlation confident). Receiver operating characteristic curve analysis indicated that CSPG4 H-SCORE has predictive value for poor prognosis (areas under the curve, 0.742 and 0.710; cut-off points, 82.5 and 177.5, respectively). Multiple Cox regression analysis revealed a statistically significant effect of lesion size (P = 0.014) and CSPG4 H-SCORE (P = 0.005) on recurrence as well as pathological type (P = 0.001) and CSPG4 H-SCORE stratified by 177.5 (P = 0.039). Our survival data indicated that higher CSPG4 expression was associated with a shorter time of recurrence (P = 0.003) and tumorigenesis (P<0.001). CSPG4 overexpression indicates higher risks and shorter time of postoperative VFL recurrence and tumorigenesis. Detection of CSPG4 expression in VFL may be a novel approach to assess the outcome of VFL patients.

Protocol of a decisional intervention for older adults with newly diagnosed acute myeloid leukemia and their caregivers: UR-GOAL 3.

Therapeutic advances have allowed more adults aged ≥60years with acute myeloid leukemia (AML) to receive life-prolonging treatments, with improvement in overall survival. In contrast to other cancers, the onset of AML is often sudden, high-risk treatment decisions must be made quickly, and survival is often compromised due to aging-related conditions (e.g., functional impairments). Studies have demonstrated that up to 78% of older adults with AML and their caregivers experience significant psychological distress. Distress is associated with poor quality of life, increased healthcare utilization, and increased mortality. Shared decision making (SDM) can reduce patient and caregiver distress and is essential to achieve goal-concordant care. Therefore, interventions to alleviate distress and optimize SDM in older adults with AML and their caregivers are needed. We will conduct a multicenter randomized controlled trial to evaluate the efficacy of University of Rochester-Geriatric Oncology assessment for Acute myeloid Leukemia (UR-GOAL) compared to an attention control for reducing patient distress and improving observed SDM, patient-perceived SDM, and decisional conflict. We will recruit 300 patients aged ≥60years with newly diagnosed AML, their caregivers (one caregiver per patient when available), and up to 40 oncologists from four institutions: (1) Patients will view an educational video about AML diagnosis, treatment, and prognosis; complete the Best Worst Scaling values clarification process; and review a summary report of their values with tailored question prompts and resources; (2) Caregivers will view the same educational video and receive the same summary report as patients; and (3) Oncologists will review a summary report of the patient's aging-related conditions, perception of prognosis, and values. Patients, caregivers, and oncologists will then meet during clinical visits to discuss aging-related conditions, prognosis, and patient values, and reach a treatment decision. The primary outcome measure is distress (Distress Thermometer). Secondary outcome measures include observed SDM, patient perceived SDM, and decisional conflict. This study will address significant knowledge gaps related to reducing distress and decisional conflict and improving SDM in older adults with AML. If successful, this research will inform future decisional interventions for a broader group of patients.

Construction of cuproptosis-related genes risk model predicts the prognosis of Uterine Corpus Endometrial Carcinoma

Cuproptosis, a recently discovered form of cell death, has emerged as a crucial player in tumor development, although its role in uterine corpus endometrial carcinoma (UCEC) remains inadequately explored. This study aims to identify prognostically relevant cuproptosis-related genes in endometrial cancer. Cuproptosis-related genes were sourced from previously published studies and the FerrDb database. UCEC gene expression profiles and clinical data were obtained from the TCGA database. Differential gene expression was determined using LIMMA analysis, and functional enrichment analysis was conducted on identified cuproptosis-related genes. A prognostic model for UCEC was developed using LASSO Cox regression analysis and a Nomogram, integrating survival data, status, and gene signatures. TIMER analysis assessed the impact of crucial cuproptosis-related genes on immune cell infiltration in UCEC. Validation of the selected genes, CDKN2A, GLS, and PPAT, was performed at both mRNA and protein levels. A total of 27 cuproptosis-related genes were identified, with 19 upregulated and 6 downregulated in UCEC. These genes were associated with key signaling pathways, including the TCA cycle, Pyruvate metabolism, Glycolysis/Gluconeogenesis, and Platinum drug resistance. The LASSO regression and Nomogram models demonstrated robust predictive performance for UCEC prognosis, identifying CDKN2A, GLS, and PPAT as critical prognostic genes. Furthermore, these genes played essential roles in immune cell infiltration in UCEC, confirming their significance. Validation at both mRNA and protein levels solidified the role of CDKN2A, GLS, and PPAT. The identified signature of CDKN2A, GLS, and PPAT demonstrates significant predictive value for UCEC prognosis, suggesting their potential as therapeutic targets, including their application in immunotherapy strategies.

Prognosis value of circulating telomere repeat binding factor 2 and leukocyte telomere length in breast cancer mortality

Telomere repeat binding factor 2 (TRF2) is currently a novel tumor marker, yet its clinical implication has not been investigated. The aim of this study was to investigate the prognostic value of circulating TRF2 and leukocyte telomere length in 5-year mortality in breast cancer patients. In this cohort retrospective study, breast cancer patients were included and the length of telomeres and circulating TRF2 were quantified. Receiver operating characteristics and the Youden index were used to determine the optimal cut-off. To analyze the overall survival rate in 5 years, Kaplan Meier analysis was used, while the prognostic value of both variables was analyzed in Cox proportional hazard regression on both univariate and multivariate models. Our data indicated that the optimal cut-off points for TRF2 and leukocyte telomere length were 598 pg/mL and 0.93 kb, respectively. Based on the optimal cut-off points, the participant’s data was grouped, and our data indicated that the high TRF2 group had a poorer overall survival rate in comparison to the low group (91.3% vs 83.87%; log-rank test; p&lt;0.01). The overall survival between short and long telomeres was comparable (88.24% vs 88.37%; log-rank test; p=0.64). TRF2 (hazard ratio (HR): 3.66; 95%CI: 1.45–9.29) and molecular subtype (p=0.04) were identified as independent factors to predict mortality. In conclusion, a high circulating TRF2 in breast cancer participants was associated with lower overall 5-year survival rates in comparison with the low TRF2 group. Moreover, high TRF2 could predict the mortality of the breast cancer population to be 3.66 times higher than the lower group. In contrast, telomere length was not associated with overall survival rate nor predicting mortality in five years.

Analysis of Significance of CARD11 and MYO1G Expression in Pulmonary Tuberculosis and Its Predictive Value for Prognosis of Recurrence

Pulmonary tuberculosis (PTB) is one of the most common infectious diseases worldwide, with extremely high morbidity and mortality. An in-depth understanding of the molecular pathogenesis of PTB is crucial for finding novel diagnostic and therapeutic approaches in the future. In this study, we identified 52 differentially expressed genes (DEGs), which consisted of 422 nodes and 2853 edges, from the GSE34608 dataset in the Gene Expression Omnibus (GEO) database. These DEGs were composed of 422 nodes and 2,853 edges. Functional enrichment analysis revealed that CARD11 and MYO1G are closely related to T-cell activation. Upon further clinical case analysis, we found that the expression of CARD11 and MYO1G in the peripheral blood of patients with PTB were lower than those of healthy individuals, demonstrating excellent diagnostic value for both PTB diagnosis and prognosis of recurrence. Thus, CARD11 and MYO1G are promising indicators for assessing PTB in the future.

Alterations of Krüppel-like Factor Signaling and Potential Targeted Therapy for Hepatocellular Carcinoma.

Krüppel-like factors (KLFs, total 18 members) from the zinc finger protein (ZFP) super-family have a wide range of biological functions in hepatocellular carcinoma (HCC). This paper reviews the recent some progresses of aberrant KLFs with their potential values for diagnosis, prognosis, and targeted therapy in HCC. The recent advances of oncogenic KLFs in the diagnosis, prognosis, and targeted therapy of HCC were reviewed based on the related literature on PUBMED and clinical investigation. Based on the recent literature, KLFs, according to biological functions in HCC, are divided into 4 subgroups: promoting (KLF5, 7, 8, 13), inhibiting (KLF3, 4, 9~12, 14,17), dual (KLF2,6), and unknown functions (KLF1, 15, 16, or 18 ?). HCC-related KLFs regulate downstream gene transcription during hepatocyte malignant transformation, participating in cell proliferation, apoptosis, invasion, and metastasis. Some KLFs have diagnostic or prognostic value, and other KLFs with inhibiting promoting function or over-expressing inhibiting roles might be molecular targets for HCC therapy. These data have suggested that Abnormal expressions of KLFs were associated with HCC progression. Among them, some KLFs have revealed the clinical values of diagnosis or prognosis, and other KLFs with the biological functions of promotion or inhibition might be as effectively molecular targets for HCC therapy.

Serum Cystatin S (CST4): A Novel Prognostic Marker for Gastric Cancer.

Serum Cystatin S (CST4), a secretory protein that inhibits cellular matrix degradation, significantly influences the tumor microenvironment and tumor progression. However, the prognostic value of serum CST4 in gastric cancer (GC) remains unclear. This study aims to explore serum CST4's utility in GC prognostic assessment. A cohort of 334 patients with GC who underwent radical gastrectomy was assessed. Preoperative serum CST4 levels were measured alongside traditional tumor markers, correlating with clinical data and patient outcomes. The cohort was divided into training and test sets at a ratio of 3:1 for Cox regression analyses, which identified CST4 as an independent risk factor for overall survival (OS) and disease-free survival (DFS). A prognostic model was developed, validated with calibration curves, and its predictive value was evaluated using receiver operating characteristic (ROC) curves. In addition, CST4 expression was correlated with immune cell infiltration using data from The Cancer Genome Atlas (TCGA). Patients were stratified by median CST4 levels, and Kaplan-Meier curves for OS and DFS were plotted. Cystatin S was confirmed as an independent risk factor for OS and DFS. Integrating CST4 with traditional markers and TNM pathological staging significantly enhanced the predictive value for prognosis. Cystatin S's impact on tumor progression is likely mediated through modulation of the immune microenvironment, including immune suppression and evasion. Cystatin S is an effective biomarker for GC prognostic assessment, assisting in the evaluation of prognosis and the selection of treatment strategies for patients with GC.

Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.

While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts. The IMvigor210 cohort was utilized to explore NUSAP1's association with immunotherapy efficacy. Furthermore, single-cell RNA-sequencing data was used to examine the correlation between NUSAP1 and immune cell infiltration. Finally, we analyzed the relationship between NUSAP1 and m6A methylation. NUSAP1 expression was significantly elevated in tumor tissues, correlating with poorer prognosis in LUAD patients. It exhibited a significant correlation with immune cell infiltration in the tumor microenvironment, predominantly expressed in Tprolif cells. LUAD patients with heightened NUSAP1 expression may derive greater benefit from anti-PD-L1 treatment. Additionally, NUSAP1 was tightly linked with m6A methylation. Enrichment analysis revealed its association with key biological functions, including lipid metabolism and cell cycle regulation. Our comprehensive analysis underscores NUSAP1's potential as a prognostic and immunotherapeutic biomarker for LUAD, warranting further investigation.

Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis

ABSTRACT Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. In sHLH patients, lymphocyte subset absolute numbers were significantly impaired, accompanied by T cell hyperactivation, B cell hyperactivation, and increased plasmablast proliferation. Prognostic analysis revealed that lower CD8+ T cell percentages, elevated APTT, IL-6, IL-10 levels, and increased CD4+CD28null T cell proportions were associated with poor patient outcomes. The study demonstrates dysregulation in the counts and phenotypes of lymphocyte subsets in sHLH patients. Several key factors, including IL-6, IL-10, APTT, and various T cell percentages, have potential as prognostic markers and therapeutic targets in sHLH.

Expression of Lumican and Osteopontin in Perivascular Areas of the Glioblastoma Peritumoral Niche and Its Value for Prognosis.

Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome. The secretion of extracellular matrix (ECM) proteins with anti-tumor (Lumican) and pro-tumoral (Osteopontin, OPN) properties was shown to be dependent on the regulation of GB-induced CMA in PCs. As biomarkers are rarely studied in TME, in this work, we aimed to validate Lumican and OPN as prognostic markers in the perivascular areas of the peritumoral niche of a cohort of GB patients. Previously, we had validated their expression in GB xenografted mice presenting GB infiltration (OPN) or GB elimination (Lumican) dependent on competent or deficient CMA PCs, respectively. Then, patient sample classification by GB infiltration into the peritumoral brain parenchyma was related to GB-induced CMA in microvasculature PCs, analyzing the expression of the lysosomal receptor, LAMP-2A. Our results revealed a correlation between GB-induced CMA activity in peritumoral PCs and GB patients' outcomes, identifying three degrees of severity. The perivascular expression of both immune activation markers, Iba1 and CD68, was related to CMA-dependent PC immune function and determined as useful for efficient GB prognosis. Lumican expression was identified in perivascular areas of patients with less severe outcome and partially co-localizing with PCs presenting low CMA activity, while OPN was primarily found in perivascular areas of patients with poor outcome and partially co-localizing with PCs presenting high CMA activity. Importantly, we found sex differences in the incidence of middle-aged patients, being significantly higher in men but with worse prognosis in women. Our results confirmed that Lumican and OPN in perivascular areas of the GB peritumoral niche are effective predictive biomarkers for evaluating prognosis and monitoring possible therapeutic immune responses dependent on PCs in tumor progression.

Serum levels of PSA and VEGF2 as the prognosis markers for bone metastasis of prostate cancer: A retrospective study.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in males, the mechanism of PCa with bone metastasis remains unclear. In this study, we aimed to utilize a retrospective clinical study to evaluate the diagnostic value of bone metastases from PCa and provide reference values for future applications. We retrospectively collected a total of 200 samples including 100 PCa patients with bone metastatic and 100 without from June 2019 to August 2021. Transrectal ultrasonography (TRUS) was applied for observing the microvascular blood flow in the lesion. The serum levels of prostate specific antigen (PSA), vascular endothelial growth factor 2 (VEGF2), interleukin-6 (IL-6) and Pro-gastrin-releasing peptide (ProGRP) was determined using Enzyme-linked immunosorbent assay Kit. Regression model was constructed to analyze the risk factors for PCa with bone metastasis, the prognosis value of which was evaluated using receiver operating characteristic (ROC) curves. Ultimately, dataset GSE32269 was employed for validation. The focal blood perfusion was significantly improved in patients with bone metastasis than those without (P < 0.01). The examination results indicated that PCa patients with bone metastasis had higher levels of PSA, VEGF2, IL-6 and ProGRP than non-bone metastasis (P < 0.01). Moreover, the regression analysis indicated that the four cytokines were the risk factors for bone metastasis, and the ROC curves further confirmed that PSA and VEGF2 had high value of prediction value for bone metastasis with AUC of 0.901 and 0.8519. The expression of PSA and VEGF2 in serum had high prognosis value for bone metastasis in PCa patients.

Combined collaterals and hemodynamic features to predict the prognosis in acute ischemic stroke patients undergoing mechanical thrombectomy

BackgroundDespite successful recanalization via mechanical thrombectomy (MT), only half of acute ischemic stroke (AIS) patients achieve functional independence. Post-MT hemodynamic features are insufficiently investigated, and the lack of bilateral comparisons...

An inflammatory prognostic scoring system to predict the risk for adults with acute coronary syndrome undergoing percutaneous coronary intervention

BackgroundThis study aimed to investigate the value of the inflammatory prognostic score (IPS) system for predicting the risk of all-cause major adverse cardiovascular events (MACEs) and cardiac-related MACEs in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).MethodsOverall, 1384 patients with ACS who underwent PCI between January 2016 and December 2018 were consecutively enrolled. Demographic characteristics and related laboratory results for 11 inflammatory markers were collected. Least absolute shrinkage and selection operator (LASSO)-COX regression, Kaplan– Meier, restricted cubic spline (RCS), receiver operator characteristic curve (ROC), time-dependent ROC, and Cox hazard proportional regression were applied to explore the values of individual and IPS parameters.ResultsBased on the LASSO analysis, albumin (ALB) and monocyte-to-lymphocyte ratio (MLR) were included in the construction of the IPS system. A higher IPS was associated with a significantly worse long-term prognosis in the Kaplan–Meier analysis (log-rank p < 0.001). The Cox proportional hazards model demonstrated that the IPS was an independent risk factor for patients with ACS undergoing PCI. In addition, the IPS remained an independent prognosticator compared to the lowest tertiles. The time-dependent ROC showed satisfactory values for the long-term prognosis of different MACEs. Additionally, RCS showed a linear association with IPS, all-cause MACEs, and cardiac-related MACEs.ConclusionsA higher IPS level was associated with an increased risk in patients with ACS undergoing PCI, suggesting that the IPS may be a useful method for risk stratification in the assessment of the long-term prognosis of ACS.

Metabolic markers derived from 18F-FDG PET/CT in suspected recurrent ovarian carcinoma: predictive value for disease burden and prognosis.

This study aims to assess the role of 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in suspected recurrent ovarian carcinoma. Several clinical and PET parameters were assessed to evaluate disease burden and prognosis. We did a single-center, retrospective study in patients with suspected recurrent ovarian carcinoma who underwent 18F-FDG PET/CT. The disease burden on the scan was evaluated. We calculated several semiquantitative markers, including standard uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival analysis was done with clinical parameters, CA-125 levels, disease distribution, and metabolic markers. Fifty-two patients were included in the study. Half of the patients had suspected recurrence within 12 months of primary diagnosis. PET/CT scan suggested disease in 35 (67.3%) patients. Multiple metastatic sites were noted in 21 (40.4%) patients. Extra-abdominal metastases were seen in 15 (28.8%) patients. Eight patients had 18F-FDG avid disease despite a low CA-125 level (<35 IU). Young patients (<50 years), extra-abdominal disease, multiple metastases, and higher restaging were associated with poor outcomes. Meanwhile, treatment history, CA-125 level, and post-PET/CT treatment had no significant effect on survival. MTV@40% SUV (>17.21) and TLG@40% SUV (>68.7) had the sensitivity of 87.5% and 75% for predicting disease outcome. Recurrent ovarian carcinoma commonly presents with multiple metastasis and extra-abdominal metastases. 18F-FDG PET/CT-guided patterns of disease distribution were significant markers for poor prognosis. Disease burden on PET/CT-derived semiquantitative parameters was associated with poor outcomes.

Evaluation of Facial Trauma Severity in Cipto Mangunkusumo Hospital Using FISS Scoring System

Many scoring systems were introduced to search prognostic value in trauma patients. Facial trauma is a special trauma because it can cause many disabilities in facial function. There have been several reports on facial severity scoring system, such as Facial Injury Severity Score (FISS) and Maxillofacial Injury Severity Score (MFISS). Although these scoring systems have been introduced in many journals, they are not yet used by many clinicians because of their unawareness of its beneficiary. In this study, we want to introduce and apply these scoring systems in our maxillofacial data, thus it can be used for documentation system, as a research tool, and have prediction value for prognosis We retrospectively collected data on patients with facial trauma in Cipto Mangunkusumo Hospital in 2009. The data collected were age, gender, etiology, use of helmet, type of fracture and treatment given. Each patient then evaluated by FISS score to obtain their degree of severity. Using FISS score introduced by Bagheri, we found the average FISS score ini this evaluation was 3,37 ± 1,9, with minimum value 1 and maximum value 9. Most patients have FISS score 2 (24,7%). From FISS scoring system, we found that most of maxillofacial trauma in Cipto Mangunkusumo hospital in 2009 was mild trauma. In order to evaluate if FISS scoring system has predictive value for prognosis, a large sample and complete maxillofacial database are needed.

Prognosis and risk factors of IgA vasculitis nephritis in children

Objective: To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children. Methods: A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results: Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ²=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy (OR=5.41, 1.39, 6.02, 95%CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis (P=0.020, AUC=0.62, 95%CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions: For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.

Immunohistochemical Expression of Cyclin D1 and p16 in Invasive Breast Carcinoma and Its Association with Clinicopathological Parameters.

Invasive breast cancer (IBC) is a significant health concern globally, contributing to substantial morbidity and mortality among women. Dysregulated cellular proliferation, a hallmark of malignancy, involves molecular pathways modulated by proteins such as cyclin D1 and p16. Understanding their roles in IBC pathogenesis and their association with prognostic parameters is crucial for refining treatment strategies. This retrospective study included 50 female IBC patients who underwent modified radical mastectomy. Histopathological evaluation and immunohistochemical staining for cyclin D1 and p16 were conducted. Associations between protein expression and clinicopathological parameters were analyzed using statistical tests. Cyclin D1 was expressed in 76% of cases, significantly associated with lower tumor grade and lower Ki-67 proliferation index. It also correlated with luminal A/B molecular subtypes. p16 expression was observed in 48% of cases, significantly associated with higher tumor grade, higher Ki-67 index, and triple-negative/Her-2 neu-enriched subtypes. Co-expression of cyclin D1 and p16 was noted in 60% of cases. No significant association was found between protein expression and other parameters. Cyclin D1 and p16 exhibit potential as prognostic markers in IBC. Cyclin D1 expression correlates with less aggressive tumor features and luminal subtypes, suggesting a favorable prognosis and potential predictive value for CDK4/6 inhibitor therapy. Conversely, p16 expression associated with aggressive phenotypes, indicating poor prognosis. Further studies are warranted to validate these findings and explore their clinical implications. Integrating these biomarkers into clinical practice may enhance risk stratification and treatment decisions, ultimately improving outcomes for IBC patients.

FoxP3+ Regulatory T-Cell Quantities in Nodal T-Follicular Helper Cell Lymphomas and Peripheral T-Cell Lymphomas Not Otherwise Specified and Their Impact on Overall Survival.

The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3+ regulatory T cells (Tregs). The role of FoxP3+ Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3+ cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS. excisional lymph node (LN) biopsies from 105 nodal PTCLs and 17 reactive LNs are immunohistochemically stained for FoxP3. Visual scoring of FoxP3+ cells is performed, and different cut-off values are used to evaluate the impact of FoxP3+ cell quantity on OS. FoxP3+ cells are present in the TME of all cases, except for four cases where FoxP3+ is expressed in lymphoma cells. Lower FoxP3+ cell quantities are observed in certain nodal PTCL subtypes compared to reactive LNs. Patients with high FoxP3+ cell quantities show improved OS. However, the FoxP3+ cell quantity is not confirmed as an independent prognostic biomarker. these findings underscore the promise of FoxP3+ cell quantities as added value in prognosis and highlight the potential benefits of Treg-stimulating therapies in PTCLs.

Comprehensive Analysis Reveals That ISCA1 Is Correlated with Ferroptosis-Related Genes Across Cancers and Is a Biomarker in Thyroid Carcinoma.

ISCA1 (Iron-Sulfur Cluster Assembly 1) is involved in the assembly of iron-sulfur (Fe-S) clusters, which are vital for electron transport and enzyme activity. Some studies suggest the potential involvement of ISCA1 in tumor progression through interactions with ferroptosis-related genes (FRGs) and the tumor immune microenvironment (TME). However, there has been no systematic analysis of its role in FRGs and the TME or its predictive value for prognosis and immunotherapy response across different cancer types. In this study, we analyzed the expression and prognosis of ISCA1 RNA, CNV, methylation, and protein in multiple tumor tissues via data from the TCGA and CPTAC databases and clinical information. We conducted a comprehensive analysis of the correlations between ISCA1 and FRGs, immune-related genes (including immune regulatory genes and immune checkpoint genes), immune cell infiltration, immune infiltration scores, tumor stemness, and genomic heterogeneity. We performed drug prediction and validation through molecular docking and molecular dynamics analysis to identify candidate drugs that could promote or inhibit ISCA1 RNA expression. Our findings revealed that ISCA1 could serve as a biomarker in thyroid carcinoma, play a role with different FRGs in various cell types, and mediate different ligand-receptor pathways for cell-cell communication. Overall, our study highlights the potential of ISCA1 as a novel biomarker for predicting prognosis and immunotherapeutic efficacy in thyroid carcinoma and suggests its potential for developing novel antitumor drugs or improving immunotherapy.

BIRC5 knockdown ameliorates hepatocellular carcinoma progression via regulating PPARγ pathway and cuproptosis

BackgroundHepatocellular carcinoma (HCC) with complex molecular carcinogenesis represents a kind of prevalent neoplasm occurring in the liver. The objective of this study is to illustrate the function of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and underlying action mechanisms in HCC progression.MethodsComprehensive bioinformatics methods were conducted to screen differentially expressed genes (DEGs), cuproptosis-associated DEGs, and hub genes. The correlation between BIRC5 and immune cell infiltration, prognosis value was evaluated. The specific effects of BIRC5 silencing on HCC cells was validated by functional assays, and the impact on tumorigenicity and cuproptosis was also elucidated in vivo. Additionally, the effects of BIRC5 deficiency on PPAR pathway were determined using Oroxin A in vitro.ResultsA total of 45 cuproptosis-associated DEGs and 9 hub genes were discovered through bioinformatics. Then 6 core genes were confirmed in Hep-3B and SK-Hep-1 cells with 4 genes upregulated and 2 genes downregulated. Therein, BIRC5 was positively correlated with the infiltration of CD8+ T cells, macrophages, and highly expressed BIRC5 exhibited poor prognosis of overall survival in HCC. Furthermore, BIRC5 deletion inhibited the PPARγ pathway, thereby restraining the malignant phenotypes of HCC cells and tumorigenesis in vivo. Additionally, silencing of BIRC5 contributed to the initiation of cuproptosis in HCC.ConclusionsBIRC5 silencing attenuated HCC through blocking PPARγ pathway and regulating cuproptosis, which may offer therapeutic implications against HCC.