Prognostic Biomarker Research Articles

Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease.

Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.

A novel immune‑related lncRNA as a prognostic biomarker in HER2+ breast cancer

A novel immune‑related lncRNA as a prognostic biomarker in HER2⁺ breast cancer

Plasma Circular RNAs as Biomarkers for Breast Cancer

Breast cancer (BC) is currently the most common neoplasm, the second leading cause of cancer death in women worldwide, and is a major health problem. The discovery of new biomarkers is crucial to improve our knowledge of breast cancer and strengthen our clinical approaches to diagnosis, prognosis, and follow-up. In recent decades, there has been increasing interest in circulating RNA (circRNA) as modulators of gene expression involved in tumor development and progression. The study of circulating circRNAs (ccircRNAs) in plasma may provide new non-invasive diagnostic, prognostic, and predictive biomarkers for BC. This review describes the latest findings on BC-associated ccircRNAs in plasma and their clinical utility. Several ccircRNAs in plasma have shown great potential as BC biomarkers, especially from a diagnostic point of view. Mechanistically, most of the reported BC-associated ccircRNAs are involved in the regulation of cell survival, proliferation, and invasion, mainly via MAPK/AKT signaling pathways. However, the study of circRNAs is a relatively new area of research, and a larger number of studies will be crucial to confirm their potential as plasma biomarkers and to understand their involvement in BC.

Integrated analysis of single-cell and bulk RNA sequencing to construct a CD8 + T cell-related immune gene signature in pancreatic cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor that responds poorly to immunotherapy. The pivotal influence of CD8 + T-cell infiltration on immunotherapy has been documented in various solid tumors. However, the specific contribution of CD8 + T cell-associated immune genes (TIGs) to the tumor immune microenvironment remains unclear. Methods: We obtained CD8 + T cell-related immune genes from the INNATE and IMMPORT databases. Univariate analysis and lasso regression analysis were utilized to screen hub TIGs and develop a prognostic signature, the TIGs score. This score was used to evaluate prognosis, immunocyte infiltration, cancer-associated signaling pathways, and the potential responsiveness of immunotherapy. The transcriptomic data and single-cell data from the GSE183795 and GE212966 datasets are employed to validate the reliability of the findings. Results: Our findings suggest that patients with low TIGs scores have stronger immune effector functions and immune checkpoint activation, resulting in a more favorable response to PD-L1 inhibitors. TIGs scores were significantly correlated with various molecular characteristics and clinical outcomes, such as tumor mutation burden, multiple tumor-associated pathways, and chemotherapeutic drug sensitivity. PSME2 was identified as a potential prognostic biomarker for predicting survival in patients with PDAC. Conclusions: This study elucidates the intricate regulatory mechanisms of TIGs within the tumor immune microenvironment of pancreatic cancer. Our findings strongly suggest that the TIGs score is a robust prognostic marker for prognosis and immunotherapy responsiveness. Additionally, targeting PSME2 may offer a novel avenue for enhancing the effectiveness of immunotherapy in pancreatic cancer.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

BACKGROUND Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway.

Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/β-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on β-catenin and p-glycogen synthase kinase-3β (p-GSK-3β). Similarly, the deliberate activation of RBM5 reduced the increase in β-catenin and p-GSK-3β caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Prognostic Significance of Baseline Neutrophil to Lymphocyte Ratio and Lymphocyte to C-reactive Protein Ratio in COVID-19 Patients

Objective: Neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios are important prognostic indicators for disease severity measurement among coronavirus patients. To predict the disease severity, CURB-65 scores, and outcome after 14 days of admission using two proxy biomarkers (neutrophil lymphocyte and lymphocyte C-reactive protein ratios) in COVID-19 patients.&#x0D; Methodology: A prospective study was done at the Department of Medicine, Pakistan Ordinance Factory (POF) hospital, Wah Cantt, Pakistan, from April to August 2022. A total of 123 coronavirus patients were included. Patients with clinical manifestations, decreased lymphocyte and leukocyte counts, imaging characteristics of pneumonia, etiological evidence of a positive real time PCR test of blood or respiratory samples, and viral gene sequencing similar to known COVID-19 were measured. Patients underwent laboratory measurements and imaging analysis for biomarker indications. The analysis of the data was conducted using SPSS version 23.&#x0D; Results: The patients mean age was 53.83±16.2 years. Among 123 COVID-19 patients, 80 (65%) were males and 43 (35%) were females. It was found to have high NLR and low LCR in severe disease (p = 0.05, p = 0.01). NLR and LCR showed 11% variance for disease severity (β = 0.143, p = 0.00, and β = -0.293, p = 0.01). NLR and LCR showed 29% variance for CURB 65 scores (β = 0.48, p = 0.634, and β = -0.159, p = 0.08). NLR and LCR showed 22% variance for outcome after 14 days of admission (β=-0.53, p=0.562, &amp; β=-0.132, p=0.149).&#x0D; Conclusion: Neutrophil to lymphocyte and lymphocyte to C-reactive protein ratios are effective prognostic biomarkers for measuring the severity of disease in COVID-19 patients. High neutrophil-to-lymphocyte and low lymphocyte-to-C-reactive protein ratios significantly predict disease severity.

The Effect of Probiotics on the Prognostication of the Neutrophil-to-Lymphocyte Ratio in Severe Multi-Trauma Patients

Background: The ratio of neutrophils to lymphocytes [NLR] is one of the most accepted prognostic indices and demonstrates a positive correlation with the severity of a disease. Given that probiotics exerted immunomodulatory properties and thus positively affected lymphocytopenia induction in severely ill patients, we performed a post hoc analysis in the ProVAP protocol to investigate whether probiotics affected the prognostication of NLR in respect to ventilator-associated pneumonia in multi-trauma patients. This cohort mandatorily involved severe traumatic brain injury patients. Methods: The white blood cell data of all patients, after being retrieved for the days 0 and 7, were statistically assessed in respect to neutrophils, lymphocytes and NLR among the 4 sub-groups of the study: placebo/no-VAP, placebo/VAP, probiotics/no-VAP, and probiotics/VAP. Results: Lymphopenia was dominant in placebo sub-groups, while an increased level of lymphocytes was prominent in probiotics sub-groups. This resulted in an increase [p = 0.018] in the NLR value in the probiotics/VAP group in relation to the probiotics/no-VAP cohort; this was an increase of half the value of the placebo/VAP [p &lt; 0.001], while the NLR value in placebo/no-VAP group increased almost four-fold in relation to probiotics/no-VAP [p &lt; 0.001]. Additionally, the ROC curve for probiotic-treated patients revealed a NLR7 cut-off value of 7.20 as a prognostic factor of VAP (AUC: 78.6%, p = 0.015, 95% CI: 62.6–94.5%), having a high specificity of 90.2% and a sensitivity of 42.9%. Conclusions: NLR may considered a credible prognostic biomarker in multi-trauma patients since it can evaluate the immunomodulatory benefits of probiotic treatment. However, the results of the present post hoc analysis should be interpreted meticulously until further evaluation, since they may be basically species- or strain-specific.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential. We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD. We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways. Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.

GPR27 expression correlates with prognosis and tumor progression in gliomas

Backgrounds Glioma is a highly aggressive type of brain tumor, and its prognosis is still poor despite recent progress in treatment strategies. G protein-coupled receptor 27 (GPR27) is a member of the G protein-coupled receptor family and has been reported to be involved in various cellular processes, including tumor progression. Nevertheless, the clinical potential and tumor-related role of GPR27 in glioma remain unknown. Here we aimed to explore the function and role of GPR27 in gliomas. Methods In the current study, we evaluated the expression and clinical significance of GPR27 in gliomas using data from The Cancer Genome Atlas (TCGA) datasets. We also conducted cellular experiments to evaluate the functional role of GPR27 in glioma cell growth. Results We found that GPR27 expression level was closely associated with disease status of glioma. Of note, GPR27 was negatively correlated with WHO grade, with grade IV samples showing the lowest GPR27 levels, while grade II samples showed the highest levels. Patients with IDH mutation or 1p/19q co-deletion exhibited higher GPR27 levels. In addition, lower GPR27 levels were correlated with higher death possibilities. In cellular experiments, we confirmed that GPR27 inhibited glioma cell growth. Conclusions Our results indicate that GPR27 may function as a potential prognostic biomarker and therapeutic target in gliomas. Further studies are needed to illustrate the signaling mechanism and clinical implications of GPR27 in gliomas.

Abstract P18: RHBDL2 PROMOTES NON-SMALL CELL LUNG CANCER METASTASIS AND OSIMERTINIB RESISTANCE BY ACTIVATING RAS/MEK/ERK SIGNALING PATHWAY THROUGH INTERACTION WITH FGFR

Abstract Non-small cell lung cancer (NSCLC) is a highly malignant form of cancer, distinguished by prompt metastasis, restricted response to chemotherapy, and unfavorable prognosis. As a result, there is an imperative requirement to investigate novel therapeutic approaches for NSCLC. Rhomboid-like protein 2 (RHBDL2) is overexpressed in various tumor cells and is associated with poor prognosis. However, the relevance of RHBDL2 to NSCLC remains unclear. This study aims to investigate the potential role of RHBDL2 as a diagnostic and prognostic biomarker for NSCLC, as well as its biological functions and molecular mechanisms in NSCLC. We found that RHBDL2 was highly expressed in human NSCLC cells and tissues, and was significantly correlated with distant metastasis and poor survival of NSCLC patients. Gain- and loss-of-function assays showed that RHBDL2 could accelerate NSCLC metastasis in vitro and in vivo. KEGG/GO enrichment analysis identified that the function of RHBDL2 was significantly associated with the activity of RAS signaling pathway. RNA-Seq results also suggested that RHBDL2 might be involved in the activation of the RAS/MEK/ERK signaling pathway. ERK1/2 inhibitor Ravoxertinib could partially restore the metastatic ability of NSCLC cells mediated by RHBDL2. CO-IP/MS results suggested that RHBDL2 interacted with FGFR. GST-pulldown assay confirmed the above findings. RHBDL2 could directly interact with FGFR and affect its phosphorylation, and promote NSCLC cell migration by activating the downstream RAS/MEK/ERK signaling pathway. In addition, we also found that RHBDL2 was involved in osimertinib resistance through FGFR/RAS pathway. Our study results indicate that RHBDL2 promotes NSCLC cell migration and osimertinib resistance by interacting with FGFR and thereby activating the RAS/MEK/ERK signaling pathway. Moreover, it can serve as a novel diagnostic and prognostic biomarker for NSCLC patients. Citation Format: Jun Deng, Jia-jia Qin, Neng-ming Lin. RHBDL2 PROMOTES NON-SMALL CELL LUNG CANCER METASTASIS AND OSIMERTINIB RESISTANCE BY ACTIVATING RAS/MEK/ERK SIGNALING PATHWAY THROUGH INTERACTION WITH FGFR [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P18.

Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities

Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques.

D-Loop Mutations as Prognostic Markers in Glioblastoma—A Pilot Study

Glioblastoma, a highly aggressive brain tumor, poses significant treatment challenges. A deeper investigation into its molecular complexity is essential for the identification of novel prognostic biomarkers and therapeutic strategies, potentially improving patient outcomes in terms of survival and quality of life. While nuclear DNA mutations have been extensively studied, the role of mitochondrial DNA (mtDNA) mutations, specifically in the D-loop region, remains poorly understood. This prospective case-control study aimed to assess the prognostic significance of the mtDNA D-loop m.16126T&gt;C variant in glioblastoma patients. Immunohistochemistry and droplet digital PCR (ddPCR) were employed for mutation analysis, complemented by statistical analyses and a literature review. The study cohort comprised 22 glioblastoma patients (mean age 59.36 ± 14.17, 12 (54.55%) females), and 25 controls (59.48 ± 13.22, 12 (80%) females). The D-loop m.16126T&gt;C variant was observed in four (18%) of the glioblastoma samples and was associated with shorter median survival (9.5 vs. 18 months; p = 0.016, log-rank test). This study underscores the importance of investigating mtDNA, especially D-loop variants, in glioblastoma, suggesting its potential as a prognostic biomarker and, therefore, its possible therapeutic targets, warranting further exploration.

M6A Methylation in Regulation of Antiviral Innate Immunity

The epitranscriptomic modification m6A is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of m6A machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities. In this review article, we present a comprehensive overview of the epitranscriptomic modification m6A and its implications for the interplay between viruses and their host, focusing on immune responses and viral replication. We outline future research directions that highlight the role of m6A in viral nucleic acid recognition, initiation of antiviral immune responses, and modulation of antiviral signaling pathways. Additionally, we discuss the potential of m6A as a prognostic biomarker and a target for therapeutic interventions in viral infections.

Monocytic myeloid-derived suppressor cells as an immune indicator of early diagnosis and prognosis in patients with sepsis

BackgroundImmunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis.MethodsLDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently.ResultsThe percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment.ConclusionsMDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics

BackgroundDiffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories.MethodsA panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing.ResultsThe most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL.ConclusionsThis study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

LncRNA RMST is associated with the progression and prognosis of gastric cancer via miR-204-5p

BackgroundExploring novel biomarkers for gastric cancer holds promise for enhancing patients’ therapy and survival rates. lncRNAs and miRNAs have emerged as important biomarkers for various human cancers. However, the role of lncRNA RMST (RMST) in gastric cancer development and the mechanism underlying its function remains unclear.ResultsSignificant upregulation of RMST was observed in gastric cancer tumor tissues. RMST levels showed strong correlation with patients’ lymph node metastasis and TNM stage and serving as a predictor of adverse prognosis RMST negatively regulated miR-204-5p, which in turn mediated the inhibitory effects of RMST knockdown on gastric cancer cell growth and metastasis.ConclusionRMST served as both a prognostic biomarker and tumor promoter by modulating miR-204-5p. Inhibiting RMST could represent a novel and potential therapeutic strategy for gastric cancer.

EMP2 Serves as a Functional Biomarker for Chemotherapy-Resistant Triple-Negative Breast Cancer

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

Estimation of local arterial stiffness using non-invasive flow measurements: A study on a stenosed carotid artery

Abstract Arterial stiffness is a well-established independent prognostic bio-marker in the human cardiovascular system (CVS). Despite its value&amp;#xD;as a predictive bio-marker, the inclusion of vascular stiffness into standard clinical procedures or guidelines is limited. This has come about as a result of the abundance of tools created to estimate and evaluate local arterial stiffness in people. This study employs a non-invasive technique to measure local arterial stiness in the human carotid arteries using proximal flow measurements. Within this work, a viscoelastic lumped-parameter (0D) model of the carotid arteries is developed in complement with the non-invasive &amp;#xD;ow measurements obtained from the Doppler ultrasound. Further, concepts of sensitivity analysis and parameter estimation are applied to estimate arterial stiffness using the flow measurement taken at the common carotid artery (CCA). After the successful estimation of arterial stiffness in CCA, results show good agreement between model simulations and actual measurement.