Potential Prognostic Marker Research Articles

Triglyceride-glucose index as a predictor of cardiac adverse events in acute coronary syndrome patients undergoing percutaneous coronary intervention: role of diabetes

BackgroundTriglyceride-glucose index (TyG), a surrogate marker of insulin resistance (IR), could be a potential prognostic marker in patients with acute coronary syndromes (ACS). We evaluated the effect of the TyG index on major adverse cardiac and cerebrovascular events (MACCE) in patients with ACS undergoing percutaneous coronary intervention (PCI).MethodsThis registry-based cohort study was conducted at Tehran Heart Center from 2015 to 2021 and the median follow-up duration was 378 days. The primary outcome was MACCE and the secondary outcomes were MACCE components: all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting. For comparison among TyG quartiles (Q), the log-rank test was used. Unadjusted and adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to describe the association between TyG quartiles and MACCE. A subgroup of euglycemic patients was also evaluated.ResultsA total of 13,542 patients were included. Patients in the fourth TyG quartile (Q4) were younger, had higher mean BMI, and higher prevalence of hypertension, diabetes, and dyslipidemia. The adjusted Cox model showed that a 1-unit increment of the TyG index was associated with a significantly higher risk of MACCE (aHR 1.18, 95% CI 1.08 to 1.30, p < 0.001). Among TyG quartiles, there was a higher MACCE incidence in Q4 compared to Q1 (aHR 1.29, 95% CI 1.08 to 1.53, p = 0.005). In the euglycemic subgroup of the population, there was no significant association between MACCE incidence and a 1-unit increase in TyG or among TyG quartiles.ConclusionBased on our findings, while higher TyG levels and quartiles were associated with higher rates of MACCE in ACS, there was no such effect in the euglycemic population. If confirmed in future studies, these results can be beneficial for clinicians to risk stratify these patients with an easy-to-use index and determine clinical plans based on their risk.Graphical abstract

Unveiling Functional Biomarkers in Schizophrenia: Insights from Region of Interest Analysis Using Machine Learning.

Schizophrenia is a complex and disabling mental disorder that represents one of the most important challenges for neuroimaging research. There were many attempts to understand these basic mechanisms behind the disorder, yet we know very little. By employing machine learning techniques with age-matched samples from the auditory oddball task using multi-site functional magnetic resonance imaging (fMRI) data, this study aims to address these challenges. The study employed a three-stage model to gain a better understanding of the neurobiology underlying schizophrenia and techniques that could be applied for diagnosis. At first, we constructed four-level hierarchical sets from each fMRI volume of 34 schizophrenia patients (SZ) and healthy controls (HC) individually in terms of hemisphere, gyrus, lobes, and Brodmann areas. Second, we employed statistical methods, namely, t-tests and Pearson's correlation, to assess the group differences in cortical activation. Finally, we assessed the predictive power of the brain regions for machine learning algorithms using K-nearest Neighbor (KNN), Naive Bayes, Decision Tree (DT), Random Forest (RF), Support Vector Machines (SVMs), and Extreme Learning Machine (ELM). Our investigation depicts promising results, obtaining an accuracy of up to 84% when applying Pearson's correlation-selected features at lobes and Brodmann region level (81% for Gyrus), as well as Hemispheres involving different stages. Thus, the results of our study were consistent with previous studies that have revealed some functional abnormalities in several brain regions. We also discovered the involvement of other brain regions which were never sufficiently studied in previous literature, such as the posterior lobe (posterior cerebellum), Pyramis, and Brodmann Area 34. We present a unique and comprehensive approach to investigating the neurological basis of schizophrenia in this study. By bridging the gap between neuroimaging and computable analysis, we aim to improve diagnostic accuracy in patients with schizophrenia and identify potential prognostic markers for disease progression.

LncRNA-WAL Promotes Triple-Negative Breast Cancer Aggression by Inducing β-Catenin Nuclear Translocation

Abstract Because of its insensitivity to existing radiotherapy, namely, chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to overcome. Increasing evidence has indicated abnormal Wnt/β-catenin pathway activation in TNBC but not luminal or HER2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between activated and inactivated Wnt/β-catenin pathway of TNBC tissues, lnc-WAL (Wnt/β-catenin-associated lncRNA; WAL) was selected as the top upregulated lncRNA in Wnt/β-catenin pathway activation compared with the inactivation group. RNA immunoprecipitation sequencing was used to compare the β-catenin and IgG groups, in which lnc-WAL could interact with β-catenin. Clinically, increased lnc-WAL in TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted epithelial–mesenchymal transition, the proliferation, migration, and invasion of breast cancer stem cells and TNBC cells. Mechanistically, lnc-WAL inhibited β-catenin protein degradation via AXIN-mediated phosphorylation at serine 45. Subsequently, β-catenin accumulated in the nucleus and activated the target genes. Importantly, Wnt/β-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/AXIN/β-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL may be a potential therapeutic target against TNBC. Implications: The positive feedback between lnc-WAL and the Wnt/β-catenin pathway promotes TNBC progression, and lnc-WAL could be a potential prognostic marker for patients with TNBC.

Extrachromosomal circular DNAs in prostate adenocarcinoma: global characterizations and a novel prediction model.

The role of focal amplifications and extrachromosomal circular DNA (eccDNA) is still uncertain in prostate adenocarcinoma (PRAD). Here, we first mapped the global characterizations of eccDNA and then investigate the characterization of eccDNA-amplified key differentially expressed encoded genes (eKDEGs) in the progression, immune response and immunotherapy of PRAD. Circular_seq was used in conjunction with the TCGA-PRAD transcriptome dataset to sequence, annotate, and filter for eccDNA-amplified differentially expressed coding genes (eDEGs) in PRAD and para-cancerous normal prostate tissues. Afterwards, risk models were created and eKDEGs linked to the PRAD prognosis were identified using Cox and Lasso regression analysis. The immune microenvironment of the risk model was quantified using a variety of immunological algorithms, which also identified its characteristics with regard to immunotherapy, immune response, and immune infiltration. In this research, there was no significant difference in the size, type, and chromosomal distribution of eccDNA in PRAD and para-cancerous normal prostate tissues. However, 4,290 differentially expressed eccDNAs were identified and 1,981 coding genes were amplified. Following that, 499 eDEGs were tested in conjunction with the transcriptome dataset from TCGA-PRAD. By using Cox and Lasso regression techniques, ZNF330 and PITPNM3 were identified as eKDEGs of PRAD, and a new PRAD risk model was conducted based on this. Survival analysis showed that the high-risk group of this model was associated with poor prognosis and validated in external data. Immune infiltration analysis showed that the model risks affected immune cell infiltration in PRAD, not only mediating changes in immune cell function, but also correlating with immunophenotyping. Furthermore, the high-risk group was negatively associated with anti-CTLA-4/anti-PD-1 response and mutational burden. In addition, Tumor Immune Dysfunction and Exclusion analyses showed that high-risk group was more prone to immune escape. Drug sensitivity analyses identified 10 drugs, which were instructive for PRAD treatment. ZNF330 and PITPNM are the eKDEGs for PRAD, which can be used as potential new prognostic markers. The two-factor combined risk model can effectively assess the survival and prognosis of PRAD patients, but also can predict the different responses of immunotherapy to PRAD patients, which may provide new ideas for PRAD immunotherapy.

The relationship between tumor budding and survival of patients with breast cancer: A meta-analysis.

Tumor budding has been proposed as a potential prognostic marker in various cancers, but its association with survival outcomes in breast cancer (BC) remains unclear. This meta-analysis aimed to clarify the relationship between tumor budding and survival outcomes in patients with BC. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science. Cohort studies examining the association between tumor budding and overall survival (OS) and progression-free survival (PFS) in BC patients were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for potential heterogeneity. Eleven cohort studies, including 2,828 patients, met the inclusion criteria. High tumor budding was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.37-2.60, P < 0.001) and PFS (HR = 1.89, 95% CI = 1.32-2.71, P < 0.001). Subgroup analyses revealed a stronger association in studies where high tumor budding was defined as ≥ 10 buds / high-power field (HPF) compared to those with lower cutoffs. Sensitivity analyses confirmed the robustness of the findings. This meta-analysis demonstrates that high tumor budding is associated with significantly worse OS and PFS in BC patients, underscoring its prognostic significance. These findings suggest tumor budding could be a valuable marker in clinical assessments, and further research is needed to standardize its evaluation criteria in BC.

Investigating the Role of Differentially Expressed Genes and Sex-Specific Genes in Lung Adenocarcinoma: A Transcriptomic Analysis

Lung cancer is a life-threatening disease that affects hundreds of thousands of patients every year. While conventional medicine offers effective treatments for lung cancer, the use of targeted therapy can offer patients a more favorable treatment by being as effective and by minimizing the side effects the patient experiences. The purpose of this research is to identify any differentially expressed or sex-specific genes in lung adenocarcinoma (LUAD) that can act as potential targets for treatment. Using transcriptomic profiles of LUAD tissues from The Cancer Genome Atlas, these profiles are analyzed using the TCGABiolinks library on R. The differentially expressed genes are then used to generate gene ontology, create protein association networks, and identify survival plots of genes using Metascape, STRING, and the Human Protein Atlas respectively. Similar procedures were used for the sex-specific analysis. The gene ontology analysis showed that the TFAP2 family of transcription factors and the PID HNF3B pathway likely promote tumorigenesis in LUAD. Moreover, AGER and SFTPC, genes involved in lung development, were underexpressed in all LUAD samples. Patients with a higher expression of these genes had a higher survival rate than others and can act as potential prognostic markers. In sex-specific genes, it was found that members of the MAGE-A family, a testis antigen family, were highly up-regulated in both males and females. The dysregulation of these genes in females might have a specific role in LUAD progression. These findings can be investigated further to develop better therapies to treat the disease.

Hematological Parameters at Baseline: A Novel Prognostic Factor for Cervical Cancer Patients Undergoing Concurrent Chemoradiotherapy in South India.

Introduction In cervical cancer treatment, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-globulin ratio (AGR) are being studied as potential prognostic markers for predicting the effectiveness of concurrent chemoradiotherapy (CCRT). This study aims to investigate the relationship between these biomarkers and survival outcomes in cervical cancer patients undergoing CCRT. Materials and methods This retrospective study was conducted at Amrita Institute of Medical Sciences between January 2016 and December 2019. It included patients at any stage who received definitive CCRT and were followed for at least two years post-treatment. Patients who had initial surgery and those lost to follow-up were excluded. Results The study included 123 patients with a median age of 68. Most patients had stage IIB (39%) and squamous cell carcinoma (76.4%). With a median follow-up of 56 months, the five-yearoverall survival (OS) was 66.8%, progression-free survival (PFS) was 94%, and recurrence-free survival (RFS) was 81.2%.AGR (p = 0.001), NLR (p = 0.0001), and PLR (p = 0.001) were found to be significantly associated with OS, NLR (p = 0.002) and AGR (p = 0.001) significantly affected RFS, while only PLR (p = 0.02) significantly affected PFSon univariate analysis. NLRsignificantly impacted OS (p = 0.003) and RFS(p = 0.03) on multivariate analysis. Conclusion The results of our study showed that increased NLR and elevated levels of albumin indicate a higher likelihood of mortality. Furthermore, a higher NLR was linked to an increased probability of recurrence in patients with cervical cancer who received primary treatment with CCRT. Therefore, the identification of predictive biomarkers could significantly improve the assessment of progression risk, aiding in the selection of the most suitable treatment and personalized therapy.

MISP-mediated enhancement of pancreatic cancer growth through the Wnt/β-catenin signaling pathway is suppressed by Fisetin

Pancreatic cancer is a highly malignant tumor characterized by high mortality and low survival rates. The mitotic interactor and substrate of Plk1 (MISP) is a cancer-associated protein that regulates mitotic spindle localization and is highly expressed in several malignant tumors, contributing to tumor development. However, the function and regulatory mechanisms of MISP in pancreatic cancer remain unclear. In this study, we analyzed RNA sequencing data related to pancreatic cancer from the TCGA and GEO databases, identifying MISP as a potential prognostic marker for the disease. MISP was significantly upregulated in pancreatic cancer cells and tissues compared to normal pancreatic cells and tissues. Notably, in pancreatic cancer cells, high MISP protein expression promoted cell proliferation and growth. Mechanistically, the upregulation of MISP facilitated the nuclear accumulation of β-catenin, thereby activating the Wnt/β-catenin signaling pathway and promoting pancreatic cancer growth. In search of effective inhibitors of MISP expression, we screened an FDA-approved drug library and identified Fisetin as a potential suppressor of MISP expression. Fisetin was found to downregulate the transcription factor MYB, thereby reducing MISP expression. Further experiments demonstrated that Fisetin effectively inhibited the in vitro and in vivo growth of pancreatic cancer by suppressing the MISP/Wnt/β-catenin signaling axis. In summary, our research has identified MISP as a novel therapeutic target in pancreatic cancer and uncovered its associated regulatory mechanisms.

SOX9 promotes hypoxic pulmonary hypertension through stabilization of DPP4 in pulmonary artery smooth muscle cells

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by pulmonary vascular remodeling (PVR), primarily due to the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This study aimed to investigate the role and molecular mechanism of SOX9 in hypoxic PH in rats. The findings revealed that SOX9 was upregulated in the pulmonary arteries and PASMCs of hypoxia-exposed rats. SOX9 knockdown inhibited hypoxia-induced proliferation and migration of PASMCs, reduced PVR, and subsequently alleviated hypoxia-induced PH in rats, suggesting that SOX9 plays a critical role in PH. Further investigation demonstrated that SOX9 interacted with DPP4, preventing its ubiquitin degradation in hypoxia-exposed PASMCs. DPP4 knockdown inhibited hypoxia-induced PASMC proliferation and migration, and administration of the DPP4 inhibitor sitagliptin (5 mg/kg) significantly reduced PVR and alleviated hypoxia-induced PH in rats, indicating that SOX9 contributes to PH by stabilizing DPP4. The results also showed that hypoxia induced YAP1 expression and dephosphorylation, leading to YAP1 nuclear localization. YAP1 knockdown promoted the degradation of HIF-1α in hypoxia-exposed PASMCs and inhibited hypoxia-induced proliferation and migration of PASMCs. Additionally, HIF-1α, as a transcription factor, promoted SOX9 expression by binding to the SOX9 promoter in hypoxia-exposed PASMCs. In conclusion, hypoxia promotes the proliferation and migration of PASMCs through the regulation of the YAP1/HIF-1α/SOX9/DPP4 signaling pathway, leading to PH in rats. These findings suggest that SOX9 may serve as a potential prognostic marker and therapeutic target for PH.

PLXDC1 serves as a potential prognostic marker and involves in malignant progression and macrophage polarization in colon cancer.

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor-infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2-like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2-like markers (CD206, CD163, arginase1, and interleukin 10 [IL-10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage-mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL-6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL-6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2-like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL-6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients.

Pan-cancer analysis of m1A writer gene RRP8: implications for immune infiltration and prognosis in human cancers

BackgroundRibosomal RNA Processing 8 (RRP8) is a gene associated with RNA modification and has been implicated in the development of several types of tumors in recent research. Nevertheless, the biological importance of RRP8 in pan-cancer has not yet been thoroughly and comprehensively investigated.MethodsIn this study, we conducted an analysis of various public databases to investigate the biological functions of RRP8. Our analysis included examining its correlation with pan-cancer prognosis, heterogeneity, stemness, immune checkpoint genes, and immune cell infiltration. Furthermore, we utilized the GDSC and CTRP databases to assess the sensitivity of RRP8 to small molecule drugs.ResultsOur findings indicate that RRP8 exhibits differential expression between tumor and normal samples, particularly impacting the prognosis of various cancers such as Adrenocortical carcinoma (ACC) and Kidney Chromophobe (KICH). The expression of RRP8 is intricately linked to tumor heterogeneity and stemness markers. Additionally, RRP8 shows a positive correlation with the presence of tumor-infiltrating cells, with TP53 being the predominant mutated gene in these malignancies.ConclusionOur findings suggest that RRP8 may serve as a potential prognostic marker and therapeutic target in a variety of cancer types.

Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma.

Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.

Metabolic score for insulin resistance as a predictor of mortality in heart failure with preserved ejection fraction: results from a multicenter cohort study

BackgroundThe metabolic score for insulin resistance (METS-IR) has been validated as a novel, simple, and reliable surrogate marker for insulin resistance; however, its utility for evaluating the prognosis of heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. Therefore, we aimed to analyze the association between METS-IR and the long-term prognosis of HFpEF.MethodsWe enrolled a total of 4,702 participants with HFpEF in this study. The participants were divided into three groups according to METS-IR tertiles: (Ln [2 × fasting plasma glucose + fasting triglycerides] × body mass index) / (Ln [high-density lipoprotein cholesterol]). The occurrence of primary endpoints, including all-cause mortality and cardiovascular (CV) death, was documented.ResultsThere were 3,248 participants with HFpEF (mean age, 65.7 ± 13.8 years; male, 59.0%) in total who were included in the final analysis. The incidence of primary outcomes from the lowest to the highest METS-IR tertiles were 46.92, 86.01, and 124.04 per 1000 person-years for all-cause death and 26.75, 49.01, and 64.62 per 1000 person-years for CV death. The multivariate Cox hazards regression analysis revealed hazard ratios for all-cause and CV deaths of 2.48 (95% CI 2.10–2.93; P < 0.001) and 2.29 (95% CI 1.83–2.87; P < 0.001) when the highest and lowest METS-IR tertiles were compared, respectively. In addition, the predictive efficacy of METS-IR remained significant across various comorbidity subgroups (all P < 0.05). Further, adding the METS-IR to the baseline risk model for all-cause death improved the C-statistic value (0.690 for the baseline model vs. 0.729 for the baseline model + METS-IR, P < 0.01), the integrated discrimination improvement value (0.061, P < 0.01), the net reclassification improvement value (0.491, P < 0.01), and the clinical net benefit.ConclusionsAn elevated METS-IR, which is associated with an increased mortality risk, is a potential valuable prognostic marker for individuals with HFpEF.

Prognostic Value of the Lactate/Albumin Ratio for 28-Day Mortality in Pediatric Septic Shock: A Prospective Cohort Study.

Background Septic shock remains a leading cause of mortality in children. The lactate/albumin ratio (LAR) has emerged as a potential prognostic marker for mortality in septic shock, yet most existing research focuses on adults, with limited data available for pediatric populations, particularly in Vietnam. Objectives This study aims to evaluate the prognostic utility of the LAR in predicting 28-day mortality among children aged two months to 15 years with septic shock in Vietnam. Methods We conducted a prospective cohort study involving children diagnosed with septic shock at the largest pediatric intensive care unit (PICU) in the Mekong Delta, Vietnam, from July 2022 to June 2024. Clinical and laboratory parameters, including lactate and albumin levels, were measured at the time of septic shock diagnosis. Patients were followed for 28 days, with outcomes categorized as either survival or mortality. The prognostic performance of LAR was assessed through its discrimination and calibration capabilities. Results The 28-day mortality rate was 63.4%. LAR was significantly higher in non-survivors compared to survivors (p < 0.001). The area under the receiver operating characteristic curve (AUROC) for LAR was 0.91, indicating superior discriminatory power compared to lactate alone and comparable to albumin. Using a Youden index-derived cut-off of 1.84, LAR demonstrated a sensitivity of 84.6% and a specificity of 80%. Kaplan-Meier analysis and log-rank testing revealed significantly lower survival probabilities in children with LAR ≥1.84 (p < 0.05). The Hosmer-Lemeshow test confirmed good calibration of LAR in mortality prediction (p > 0.05). Conclusion The lactate/albumin ratio exhibits excellent discriminatory and calibration properties, making it a valuable tool for predicting 28-day mortality in pediatric septic shock. This ratio should be considered for routine use in clinical practice to improve prognostic assessments in this vulnerable population.

Prostate cancer subtyping and differential methylation analysis based on the ETS family of transcription factors fusion genes

Prostate cancer (PCa) is a highly heterogeneous disease, encompassing various molecular and clinical pathological subtypes. Fusion genes play a facilitating role in the occurrence and progression of PCa. We categorized PCa samples into the ETS family of transcription factors fusion positive and fusion negative subtypes based on fusion genes. This subtyping method is closely related to the epigenomic DNA methylation profiles of PCa, with each sample cluster including more than 85% of the patients. We conducted an analysis of the distribution of the ETS family fusion genes on chromosomes, fusion modes within reading frames, and predictions of structural domains. Among these, the highest frequency of the ETS family related fusion genes occurred on chromosome 21. Compared to the parental genes, fusion genes exhibited new structural domains, such as IG_like, and the most common fusion mode was out-of-frame fusion. The correlation between the methylation levels of hypermethylated CpG sites and the expression levels of their corresponding mRNAs indicates that CD8A and B3GNT5 (with correlations of − 0.388 and − 0.253, respectively) could serve as potential prognostic markers for PCa.

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association

IntroductionBladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. Material and methodsA total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. ResultIn high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. ConclusionThe upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Exploring the Usefulness of Tumor Budding as a Histopathological Marker Compared to Tumor-Node-Metastasis (TNM) Staging in Breast Cancer.

Tumor budding, defined as small clusters of tumor cells at the invasive front of carcinomas, has gained attention as a potential prognostic marker in various cancers. This study aimed to evaluate the utility of tumor budding as a histopathological marker in breast cancer and compare it to traditional prognostic markers such as histological grading, tumor-node-metastasis (TNM) staging, and molecular subtypes. A prospective, cross-sectional study was conducted over two years (June 2022 to May 2024) in the Department of Pathology at Jawaharlal Nehru Medical College, Wardha. Seventy-two female patients diagnosed with breast carcinoma who underwent modified radical mastectomy were included. Tumor budding was assessed through histopathological analysis and categorized as high or low. Statistical correlations were established between tumor budding and tumor size, histological grade, lymph node involvement, vascular invasion, and molecular subtypes (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and triple-negative breast cancer, TNBC). The chi-square test and multiple regression analyses were applied to assess significance. High tumor budding was observed in 68.1% of patients and was significantly associated with larger tumor size (p = 0.040), higher histological grade (p = 0.009), lymph node metastasis (p = 0.002), and vascular invasion (p = 0.003). The postmenopausal age group (>55 years) demonstrated a higher prevalence of high budding (p = 0.010). No significant correlation was found between tumor budding and molecular subtypes (p = 0.39), although high budding was more frequent in TNBCcases. Tumor budding is significantly associated with more aggressive tumor characteristics in breast cancer. Incorporating tumor budding into routine pathological assessments alongside TNM staging and histological grading may enhance the ability to identify high-risk patients and guide treatment strategies. Further large-scale, multicenter studies are warranted to confirm its prognostic value.

Systematic pan-cancer analysis identifies DNASE2 as a potential prognostic marker and immunotherapeutic target for glioblastoma multiforme

Systematic pan-cancer analysis identifies DNASE2 as a potential prognostic marker and immunotherapeutic target for glioblastoma multiforme

Virus-Induced Host Chemokine CCL2 in COVID-19 Pathogenesis: Potential Prognostic Marker and Target of Anti-Inflammatory Strategy.

A wide variety of inflammatory mediators, mainly cytokines and chemokines, are induced during SARS CoV-2 infection. Among these proinflammatory mediators, chemokines tend to play a pivotal role in virus-mediated immunopathology. The C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1) is a potent proinflammatory cytokine and strong chemoattractant of monocytes, macrophages and CD4+ T cells bearing C-C chemokine receptor type-2 (CCR2). Besides controlling immune cell trafficking, CCL2 is also involved in multiple pathophysiological processes including systemic hyperinflammation associated cytokine release syndrome (CRS), organ fibrosis and blood coagulation. These pathological features are commonly manifested in severe and fatal cases of COVID-19. Given the crucial role of CCL2 in COVID-19 pathogenesis, the CCL2:CCR2 axis may constitute a potential therapeutic target to control virus-induced hyperinflammation and multi-organ dysfunction. Herein we describe recent advances on elucidating the role of CCL2 in COVID-19 pathogenesis, prognosis, and a potential target of anti-inflammatory interventions.

To investigate the role and potential mechanism of has_circ_RBMS3 in bone metastasis of breast cancer based on bioinformatics.

Circular RNAs (circRNAs) play a crucial regulatory role in malignant tumor metastasis. This study focused on the role of bone metastasis-related circRBMS3 in breast cancer. Two circRNA microarray datasets were obtained from the GEO database and overlapped bone metastasis-related circRNAs in breast cancer. CircRBMS3 expression was validated in bone metastasis tissues by RT-qPCR. Cellular CCK-8 assay and Transwell assays were performed to measure the effect of circRBMS3 in breast cancer cells. Bioinformatic analyses were performed to identify the binding miRNAs of circRBMS3 and downstream mRNAs. Online database STRING and Cytoscape software were used to analyze PPI interaction and conduct the ceRNA network. GEO database analysis showed that circRBMS3 was one of the upregulated circRNAs among all the metastatic cells. CircRBMS3 was increased in bone metastasis breast cancer tissues compared to non-bone metastasis tissues and associated with poor 3-year overall survival. CircRBMS3 knockdown repressed breast cancer cell proliferation, migration, and invasion, as well as bone resorption gene and osteoclast phenotype gene expression. CircRBMS3 was found to bind withmiR-654-3p. Subsequently, downstream mRNAs were predicted, and the circRBMS3 miR-654-3p-mRNA network was established. In conclusion, circRBMS3 expression was upregulated in bone metastasis breast cancer and might be a potential prognostic marker for patients. Silencing circRBMS3 restrained breast cancer cell proliferation, migration, and invasion, as well as associated with bone metastasis. The circRBMS3-miR-654-3p-mRNAs network elucidated potential mechanisms underlying bone metastasis in breast cancer.