Potential Prognostic Marker Research Articles

Circulating medium- and long-chain acylcarnitines are associated with plasma P-tau181 in cognitively normal older adults.

Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P-tau181), a recognised AD biomarker, has been described to reflect early-stage cortical amyloid-β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P-tau181 at the pre-clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P-tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted-mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)-Aβ load. In addition, the P-tau181-linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN Aβ- and CN Aβ+ individuals. Significant positive associations of medium- and long-chain acylcarnitines (ACs) were observed with P-tau181 in the entire cohort, CN Aβ- and CN Aβ+, suggesting a link between initial Aβ pathology and fatty acid oxidation-mediated energy metabolism pathways. However, in CN Aβ-, additional linear associations of P-tau181 were observed with muscle metabolism and nitric oxide homeostasis-associated metabolites. Upon investigating the P-tau181-linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN Aβ+ with medium- and long-chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET-Aβ load and inverse associations with hippocampal volume in CN Aβ+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET-Aβ status in older adults. Therefore, plasma P-tau181-linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross-sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings.

Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma

Epithelial ovarian carcinoma (EOC) is the most fatal among female reproductive system tumors. The immune tumor microenvironment and ubiquitin-proteasome pathway are closely related to the proliferation, invasion, and response to chemotherapy in EOC. However, their specific roles in EOC have not been fully elucidated. Therefore, we aimed to recognize potential prognostic markers and novel therapeutic targets for EOC. We constructed the ubiquitin-related signature risk model comprising HSP90AB1, FBXO9, SIGMAR1, STAT1, SH3KBP1, EPB41L2, DNAJB6, VPS18, PPM1G, AKAP12, FRK, and PYGB, specifically for patients with EOC. The high-risk model presented a worse prognosis, primarily associated with the B-cell receptor signaling pathway, ECM receptor interaction, focal adhesion, and actin cytoskeleton regulations. Analysis of the immune landscape revealed a higher abundance of B cells, M2 macrophages, neutrophil CD4 T cells, cancer-associated fibroblasts, macrophage neutrophils, and fibroblasts in the high-risk group. It also exhibited lower tumor mutation burden, mRNAsi, and EREG-mRNAsi and reduced sensitivity to other chemotherapy drugs, except dasatinib. These findings serve as a valuable indicator for personalized treatment strategies and clinical stratification in managing patients with EOC. Additionally, our study will serve as a foundation for future mechanistic research to explore the association between the ubiquitin-proteasome pathway and EOC.

A potential target of GXYLT2 affecting the prognosis of gastric cancer by enhancing the EMT process: A clinical retrospective study.

The present study aimed to investigate glucoside xylosyltransferase 2 (GXYLT2) as a potential prognostic marker for gastric cancer (GC). The expression levels of GXYLT2, Notch1, E-cadherin and vimentin in GC and adjacent tissues were detected by Elivision™️ Plus immunohistochemistry. The relationship between GXYLT2, Notch1, E-cadherin and vimentin, and clinicopathological parameters was also analyzed. Univariate and multivariate Cox regression analyses were conducted to evaluate the effect of GXYLT2 on survival. The results revealed that GC tissues exhibited a marked increase in GXYLT2, Notch1 and vimentin, and a marked reduction in E-cadherin. The expression of GXYLT2 was related to the differentiation degree of GC and the pathological tumor-node-metastasis (pTNM) stage; the expression of Notch1 was related to the vascular and nerve infiltration of GC; and E-cadherin and vimentin expression were related to patient age, tumor size, tumor differentiation degree, depth of infiltration, lymph node metastasis and pTNM stage. Positive associations existed between GXYLT2 and Notch1 expression, GXYLT2 and vimentin expression, and Notch1 and vimentin expression. Furthermore, the Kaplan-Meier analysis showed that survival and prognosis were associated with factors such as GXYLT2 protein levels, pTNM stage, tumor dimensions, depth of infiltration and lymph node metastasis. Through Cox regression analysis, GXYLT2 was identified as an independent predictor for GC. In conclusion, GXYLT2 may be related to the pathogenesis of GC, and its abnormal expression could be associated with epithelial-mesenchymal transition. Consequently, GXYLT2 may be considered a promising prognostic marker in the context of GC.

Programmed Death-Ligand 1 (PD-L1) and Ki-67 Labeling Index: Correlation with Tumor Grade and Recurrence

Background: Meningiomas are common primary brain tumors with variable clinical behavior. While most are benign, a subset exhibits aggressive characteristics and a high recurrence rate. This study aimed to investigate the association of Programmed Death-Ligand 1 (PD-L1) and Ki-67 labeling index with histopathological grade and recurrence in meningioma. Methods: A retrospective study was conducted on 139 cases of meningioma diagnosed between January 2020 and December 2023. PD-L1 expression was evaluated using immunohistochemistry (IHC) and scored using the combined positive score (CPS). Ki-67 labeling index was determined as the percentage of tumor cells with positive nuclear staining. The association of PD-L1 and Ki-67 with histopathological grade and recurrence was analyzed. Results: PD-L1 expression was positive in 66.7% of cases and was significantly associated with recurrence (p = 0.006). A higher Ki-67 labeling index (>4%) was observed in 68.9% of cases and was also significantly associated with recurrence (p = 0.013). No significant association was found between PD-L1 expression or Ki-67 labeling index and histopathological grade. Conclusion: PD-L1 expression and Ki-67 labeling index may serve as potential prognostic markers for predicting recurrence in meningioma. Further studies are needed to validate these findings and explore their potential therapeutic implications.

Comprehensive analysis of the expression level, prognostic value, and immune infiltration of cuproptosis-related genes in human breast cancer.

As a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer. The expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above. Compared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years. This study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.

Prognostic significance and biological implications of SM-like genes in mantle cell lymphoma

BackgroundSM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood.MethodsWe analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival.ResultsFive of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group. Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity.ConclusionsThe LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions.

The Utility of PRAME and Ki-67 as Prognostic Markers for Cutaneous Melanoma.

Cutaneous melanoma can lead to metastasis, and it is associated with high mortality. Currently, there are no widely accepted immunohistochemistry markers for melanoma prognosis in routine staging. Preferentially expressed antigen in melanoma (PRAME) is a possible biomarker for prognosis in several noncutaneous neoplasms. Ki-67 is a cell proliferation marker correlated with poor outcomes in many cancers. This study assessed PRAME and Ki-67 as potential prognostic markers for sentinel lymph node outcomes and survival among melanoma patients. This is a retrospective study analyzing cutaneous melanoma cases from a Brazilian cancer center (2005-2021). All cases were tested using immunohistochemistry to evaluate PRAME expression and Ki-67 index. Descriptive analysis, Spearman correlations, means comparison, Kaplan-Meier analysis, χ2, and Cox models were performed. In univariate analysis of 123 cutaneous melanoma cases, high extent (P = 0.0267) and elevated intensity (P = 0.043) of PRAME were associated with decreased overall survival. The Ki-67 index was associated with overall survival (P = 0.05) and sentinel lymph node status (P = 0.0403), with a positive correlation between the markers (P = 0.0004) and between Ki-67 and Breslow thickness (P = 0.0001). However, in multivariate analysis, only Breslow thickness significantly influenced overall survival (P = 0.0003). Then, the present results can suggest that elevated PRAME and Ki-67 expression are associated with poor overall survival in cutaneous melanoma; however, in multivariate analysis, only the Breslow thickness had a significant influence. These findings highlight the potential of PRAME and Ki-67 as prognostic markers, opening frontiers that could improve strategies for treating cutaneous melanoma.

HLA-G expression associates with immune evasion muscle-invasive urothelial cancer and drives prognostic relevance.

Urothelial bladder cancer is frequent and exhibits diverse prognoses influenced by molecular subtypes, urothelial subtype histology, and immune microenvironments. HLA-G, known for immune regulation, displays significant membranous expression in tumor tissues. We studied the protein expression of Human Leucocyte Antigen G (HLA-G) in 241 Muscle-Invasive Bladder Cancer (MIBC) patients, elucidating its potential clinical and biological significance. Protein expression levels were evaluated and correlated with molecular subtypes, histological characteristics, immune microenvironment markers, and survival outcomes. High HLA-G expression associates with poor overall survival (OS) and diseasespecific survival (DSS), independent of clinicopathological parameters. HLA-G expression varies among molecular subtypes and Urothelial Subtype Histology, e.g., elevated expression levels in basal/squamous MIBC and those with sarcomatoid differentiation. Notably, HLA-G is increased in MIBC with an immune evasive microenvironment (high PD-L1 tumor cell expression, NK cell depletion, granzyme B (GZMB)/CD8 ratio reduction, MHC class I (MHCI) expression reduction) that are characterized by immunosuppressive features and poor prognosis. Furthermore, HLA-G correlates with elevated levels of other immune checkpoint proteins (TIGIT, LAG3, CTLA-4), indicating its role in immune evasion. Our findings underscore HLA-G's role as a potential prognostic marker and interesting immunotherapeutic target in MIBC. Its impact on immune evasion mechanisms and broad expression, coupled with associations withpoor survival and distinct tumor phenotypes, positions HLA-G as a promising protein for further exploration in developing targeted immunotherapies for MIBC patients.

Prospective assessment of circulating tumor DNA in patients with metastatic uveal melanoma treated with tebentafusp

Tebentafusp, a bispecific immune therapy, is the only drug that demonstrated an overall survival benefit in patients with metastatic uveal melanoma (MUM). Circulating tumor DNA (ctDNA) has emerged as a potential prognostic and predictive marker in the phase 3 IMCgp100-202 trial using multiplex PCR-based next-generation sequencing (NGS). In this study (NCT02866149), ctDNA dynamics were assessed using droplet digital PCR (ddPCR) in 69 MUM patients undergoing tebentafusp treatment. Notably, 61% of patients exhibited detectable ctDNA before treatment initiation, which was associated with shorter overall survival (median 12.9 months versus 40.5 months for patients with undetectable ctDNA; p < 0.001). Patients manifesting a 90% or greater reduction in ctDNA levels at 12 weeks demonstrated markedly prolonged overall survival (median 21.2 months versus 12.9 months; p = 0.02). Our findings highlight the potential of ddPCR-based ctDNA monitoring as an economical, pragmatic and informative approach in MUM management, offering valuable insights into treatment response and prognosis.

Emerging insights into ferroptosis in cholangiocarcinoma (Review).

Cholangiocarcinoma (CCA) is a malignant tumor that arises within the biliary system, which exhibits a progressively increasing incidence and a poor patient prognosis. A thorough understanding of the molecular pathogenesis that drives the progression of CCA is essential for the development of effective molecular target therapeutic approaches. Ferroptosis is driven by excessive iron accumulation and catalysis, lipid peroxidation and the failure of antioxidant defense systems. Key molecular targets of iron metabolism, lipid metabolism and antioxidant defense systems involve molecules such as transferrin receptor, ACSL4 and GPX4, respectively. Inhibitors of ferroptosis include ferrostatin-1, liproxstatin-1, vitamin E and coenzyme Q10. By contrast, compounds such as erastin, RSL3 and FIN56 have been identified as inducers of ferroptosis. Ferroptosis serves a notable role in the onset and progression of CCA. CCA cells exhibit high sensitivity to ferroptosis and aberrant iron metabolism in these cells increases oxidative stress and iron accumulation. The induction of ferroptosis markedly reduces the ability of CCA cells to proliferate and migrate. Certain ferroptosis agonists, such as RSL3 and erastin, cause lipid peroxide build up and GPX4 inhibition to induce ferroptosis in CCA cells. Current serological markers, such as CA-199, have low specificity and cause difficulties in the diagnosis of CCA. However, novel techniques, such as non-invasive liquid biopsy and assays for oxidative stress markers and double-cortin-like kinase 1, could improve diagnostic accuracy. CCA is primarily treated with surgery and chemotherapy. A close association between the progression of CCA with ferroptosis mechanisms and related regulatory pathways has been demonstrated. Therefore, it could be suggested that multi-targeted therapeutic approaches, such as ferroptosis inducers, iron chelating agents and novel modulators such as YL-939, may improve treatment efficacy. Iron death-related genes, such as GPX4, that are highly expressed in CCA and are associated with a poor prognosis for patients may represent potential prognostic markers for CCA. The present review focused on molecular targets such as p53 and ACSL4, the process of targeted medications in combination with PDT in CCA and the pathways of lipid peroxidation, the Xc-system and GSH-GPX4 in ferroptosis. The present review thus offered novel perspectives to improve the current understanding of CCA.

Nomograms predicting benefit after immunotherapy in oral bifidobacteria supplementation ICC patients: a retrospective study

PurposeThe objective of this study was to develop nomograms for predicting outcomes following immunotherapy in patients diagnosed with intrahepatic cholangiocarcinoma (ICC).Patients and methodsA retrospective analysis was conducted on data from 75 ICC patients who received immunotherapy at Jinling Hospital and Drum Hospital. The discriminative power, accuracy, and clinical applicability of the nomograms were assessed using the concordance index (C-index), calibration curve, and decision curve analysis (DCA). The predictive performance of the nomograms for overall survival (OS) and progression-free survival (PFS) was evaluated using the area under the receiver operating characteristic (ROC) curve. Kaplan-Meier curves were also generated for validation purposes.ResultsMultivariable analysis identified independent prognostic factors for OS, including CA19-9 levels, portal vein tumor thrombus (PVTT) grade, bifidobacteria administration, and surgery. The C-index of the nomogram for OS prediction was 0.722 (95% confidence interval [CI]: 0.661–0.783). Independent prognostic factors for PFS included CA19-9 levels, albumin, and bilirubin, with a C-index of 0.678 (95% CI: 0.612–0.743) for the nomogram predicting PFS. Calibration curves demonstrated strong concordance between predicted and observed outcomes, while DCA and Kaplan-Meier curves further supported the clinical utility of the nomogram.ConclusionThe nomogram developed in this study demonstrated favorable performance in predicting the prognosis of ICC patients undergoing immunotherapy. Additionally, our findings, for the first time, identified probiotics as a potential prognostic marker for immunotherapy. This prognostic model has the potential to enhance patient selection for immunotherapy and improve clinical decision-making.

Bioinformatics analysis and experimental validation of C6orf120 as a potential prognostic marker and therapeutic target for liver hepatocellular carcinoma.

The C6orf120 gene is a novel gene whose function has not been fully defined. Previous studies have associated it with various liver pathologies, but its specific role in hepatocellular carcinoma (LIHC) remains unclear. This study aimed to investigate the diagnostic and prognostic value of C6orf120 in LIHC, as well as its potential biological functions. In this preliminary research, we utilized data from various databases and bioinformatics tools, including TCGA, GEO, TIMER2, HPA, GEPIA, Linkeomics, Metascape, CIBERSORT, TargetScan, DIANA-microT, RNAinter, and ENCORI, to analyze the expression patterns and mechanisms of C6orf120 in LIHC. Our bioinformatics analysis revealed that C6orf120 is upregulated in LIHC and may serve as a diagnostic and prognostic biomarker. The aberrant expression of C6orf120 in LIHC was further supported by clinical samples and cell lines. In vitro experiments demonstrated that the knockdown of C6orf120 in HepG2 cells significantly reduced migration capacity without affecting proliferation. Additionally, the downregulation of C6orf120 in LIHC cells appeared to inhibit endothelial cell migration and angiogenesis, which are critical in tumorigenesis and development. In conclusion, our findings suggest that C6orf120 could serve as a novel diagnostic and prognostic biomarker for LIHC and is expected to be a prognostic marker and a potential therapeutic target in the clinical management of LIHC.

Selenoprotein S (SELENOS) is a potential prognostic biomarker for brain lower grade glioma

BackgroundSelenium, an essential micronutrient, primarily exists as selenocysteine in various selenoproteins. Selenoprotein S (SELENOS) is crucial in the development of human cancer. This study aimed to explore the correlation between SELENOS gene expression and the prognosis of brain lower-grade glioma (LGG). MethodsSELENOS protein and mRNA expression in human normal and tumor tissues were explored through the HPA database. SELENOS expression differences between normal and tumor tissues, along with its prognostic significance in gliomas, were analyzed using the TCGA, GTEx datasets, while the CGGA dataset was used to further assess its prognostic potential in a Chinese cohort. The association between SELENOS expression and tumor immune infiltration was also assessed. Multivariate and univariate Cox models were used to screen for clinicopathological parameters associated with SELENOS expression. The GDSC datasets was utilized to explore the connection between SELENOS and chemotherapeutic responses in LGG. A protein-protein interaction network for SELENOS was created. SELENOS expression in LGG cell lines were determined by Western blotting and qRT-PCR, and its functions were ascertained by routine in vitro experiments. ResultsSELENOS was upregulated in 11 cancers and downregulated in 10 cancers relative to the corresponding normal tissues, and correlated significantly with the prognosis, especially for GBM, LGG and GBMLGG. Furthermore, It displayed a positive correlation with immune cell infiltration levels in LGG. Multivariate and Univariate Cox analyses confirmed that the impact of SELENOS on the prognosis of LGG is the combined result of factors such as age and tumor grade. The expression of SELENOS was significantly negatively correlated with temozolomide IC50 in LGG. We found that SELENOS interacts with 10 proteins, which are upregulated in LGG compared to human normal tissues. The expression of these interactors is positively correlated with SELENOS expression and LGG survival/prognosis. In vitro experiments confirmed the aberrant expression of SELENOS in LGG cell lines, and siRNA-mediated knockdown of SELENOS reduced the proliferation, viability, invasion and migration of LGG cells, and induced apoptosis. ConclusionsSELENOS is a potential prognostic marker and therapeutic target for LGG, and its low expression is associated with favorable prognosis in LGG.

Exploring Lysophosphatidylcholine as a Biomarker in Ischemic Stroke: The Plasma-Brain Disjunction.

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

KRT14 as a potential prognostic marker for metastasis in metaplastic breast carcinoma

Metaplastic breast cancer (MBC) is an aggressive breast cancer subtype with poor prognosis. To elucidate underlying genomic aberrations driving MBC, we conducted integrated transcriptomic analyses of MBC tumors and basal breast cancer cell lines with various transitioning phases (xE = epithelial phase clone, xM = mesenchymal phase clone and xEM = Epithelial-mesenchymal clone). Differential gene expression analysis between MBC vs non-MBC samples as well as between epithelial-mesenchymal (xEM) transitioning cells vs parental cells revealed 12 commonly dysregulated genes intersected from both the datasets meditates pathways governing EMT, migration, proliferation and metastasis. Further investigation onto those genes based on multi-omics approaches that include survival analysis, correlated expression patterns and interactomics indicated KRT14 had a key role in promoting MBC aggression through Epithelial mesenchymal transition leading to metastasis. Moreover, NPR3 was found to be a possible link between KRT14 and EMT in metastasis. To our knowledge, this is the first evident gene expression study to investigate the potential association between the expression of KRT14 and NPR3 and metastasis in MBC, and their potential involvement in the epithelial-mesenchymal transition (EMT) process. These mechanistic and prognostic insights gained can lead to targeted therapeutics against this rare, refractory disease. Overall, this work highlights the effectiveness of integrated multi-omics in revealing gene expression pattern and predictive biomarkers for metaplastic breast cancer subtypes with poor prognosis.

Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients

ObjectiveAs the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited.MethodsThirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses.ResultsThe ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test).ConclusionsThis study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.

KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer

BackgroundAs one of the most prevalent cancers, gastric cancer (GC) exhibits a remarkably high morbidity and mortality rate. To date, effective diagnostic and prognostic markers and therapeutic targets for GC are still lacking. Kinetochore associated 1 (KNTC1) is one of the proteins involved in chromosome segregation. However, the diagnostic and prognostic value of KNTC1 and its biological function in GC remain unknown. MethodsIn this study, Gene Expression Omnibus (GEO) datasets were utilized to identify differentially expressed genes (DEGs). Prognostic and diagnostic value were assessed by Kaplan-Meier plotter and receiver operating characteristic (ROC) curve. The expression of KNTC1 was verified by q-PCR, immunohistochemistry (IHC) and Western blotting. Subsequently, KNTC1 knockdown was employed to investigate its effect on GC cells. Gene set enrichment analysis (GSEA) revealed a pathway regulated by KNTC1, which was further verified by Western blotting. ResultsFour highly expressed genes (ESPL1, RAD54L, KNTC1, TACC3) were identified as biomarkers for GC diagnosis and prognosis. Notably, the value of KNTC1 as a biomarker for GC was newly revealed. Single-cell and immune analyses revealed that KNTC1 contributed to the suppression of the GC immune microenvironment. In clinical samples, we demonstrated high expression of KNTC1 in GC tissues. KNTC1 knockdown suppressed proliferation and migration while promoting apoptosis of GC cells. Additionally, KNTC1 may affect GC cells by regulating the PI3K/Akt/mTOR pathway. ConclusionsKNTC1 acts as a potential diagnostic and prognostic marker for GC. It may promote proliferation and migration while inhibiting apoptosis of GC cells via the PI3K/Akt/mTOR pathway.

Assessment of Serum Pentraxin 3 Level in Critically Ill Pediatric Patients with COVID 19 Infection and Multisystem Inflammatory Syndrome in Children (MIS-C) Related to COVID 19

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but severe condition that has been observed in pediatric patients following COVID-19 infection. The identification of prognostic markers for MIS-C is crucial for early detection and appropriate management. Two potential prognostic markers that have been studied in relation to MIS-C are pentraxin 3 (PTX3) and procalcitonin. Aim To assess serum Pentraxin 3 level in COVID-19 infection pediatric patients and Multisystem Inflammatory Syndrome in Children (MIS-C) related to COVID-19. Methods This is a cohort study consisting of (75) children, joined through consecutive method. They were assigned into 3 groups, pediatric patients with COVID-19, Pediatric patients with MIS-C related to COVID-19, as well as healthy controls matching age and gender in both groups. In addition, patients were mainly assessed for serum Pentraxin 3, and Serum Procalcitonin levels by ELISA. Results we included 28 patients in the Covid-19 group, and 29 patients in the MIS-C group with median age of 31.5 months, and 84 months, respectively. We found that the median Pentraxin 3 (PTX3), and Procalcitonin (PCT) levels were significantly higher in the Covid 19 group than the MISC and control groups with values of (11.8 ng/mL), (5.2 ng/mL), and (1.5 ng/mL), respectively; and (799.6 ng/mL), (691.6 ng/mL), and (0.03 ng/mL), respectively. As regards vital signs in the two groups, MIS-C patients had significantly higher temperature, and oxygen saturation with (38.45 °C vs. 37.70 °C), and (98.48% vs. 95.32%), respectively. Regarding laboratory investigations, Ferritin, and CRP, MIS-C group had significantly higher values with (743 vs 290 µg/L), and (188, and 38), respectively. As regards correlation between Pentraxin 3 (PTX3), and Procalcitonin (PCT) with symptoms and laboratory investigations in the MIS-C group, PTX3 showed significant positive correlation with dehydration, hypotension, and creatinine level, (R = 0.108, 0.128, and 0.106), and (P = 0.001, 0.022, and 0.048), respectively. While Procalcitonin (PCT) showed significant positive correlation with dehydration, and Sequential Organ Failure Assessment (SOFA score) (R = 0.439, and 0.4), and (P = 0.036, and 0.032), respectively, in addition, it showed significant negative correlation with EF% (R=-0.511), and (P = 0.005). Regarding correlation between Pentraxin 3 (PTX3), and Procalcitonin (PCT) with symptoms and laboratory investigations in the Covid-19 group, they both had positive correlation duration of fever (R = 0.433, and 0.108), and (P = 0.021, and 0.585). On the other hand, oxygen saturation demonstrated an inverse correlation with Procalcitonin R=-0.376), and (P = 0.049), but not with Pentraxin 3. Conclusion it’s concluded that PTX3, and PCT levels significantly increase in Covid-19 patients, and MIS-C patients. Not only that, but they are significantly higher in the Covid-19 group than the MIS-C group.

Comprehensive evaluation of immunological attributes and immunotherapy responses of positive T cell function regulators in colorectal cancer

BackgroundPositive regulators of T-cell function (PTFRs), integral to T-cell proliferation and activation, have been identified as potential prognostic markers in colorectal cancer (CRC). Despite this, their role within the tumor microenvironment (TME) and their response to immunotherapy are not yet fully understood.MethodsThis study delved into PTFR-related CRC subtypes by analyzing four independent transcriptome datasets, emphasizing the most significant prognostic PTFRs. We identified differentially expressed genes (DEGs) between two subtypes and developed a PTFR risk model using LASSO and Cox regression methods. The model’s associations with survival time, clinical features, TME characteristics, tumor mutation profiles, microsatellite instability (MSI), cancer stem cell (CSC) index, and responses to chemotherapy, targeted therapy, and immunotherapy were subsequently explored.ResultsThe PTFR risk model demonstrated a strong predictive capacity for CRC. It facilitated the estimation of immune cell composition, HLA expression levels, immune checkpoint expression, mutation burden, CSC index features, and the effectiveness of immunotherapy.ConclusionsThis study enhances our understanding of the role of PTFRs in CRC progression and introduces an innovative assessment framework for CRC immunotherapy. This framework improves the prediction of treatment outcomes and aids in the customization of therapeutic strategies.

Evaluation of sRAGE as a New Diagnostic and Prognostic Marker of Sepsis and Septic Shock Cases on Critically Ill Pediatric Patients

Abstract Background Serum sRAGE is a soluble isoform of a receptor for advanced glycation end products in different stages of sepsis. The present study will investigate the possible use of sRAGE as a diagnostic and prognostic marker of sepsis and septic shock in pediatric patients. Objective To study the role of sRAGE as a potential diagnostic and prognostic marker in sepsis and septic shock in pediatric intensive care unit. Patients and Methods This was a case control study that was conducted at Pediatric ICU, Ain Shams University Hospitals. This Studied were divided into 3 groups: 1/ Sepsis group (20 patients). 2/ Septic shock group (20 patients). 3/ healthy control group (40 child). Results In Sepsis cases, ROC curve analysis proved good discriminating power of the Serum RAGE between Non Survivor group and Survivor group where Area under the ROC curve (AUC) = 0.760 with (95% Confidence interval 0.52–0.92); p &amp;lt; 0.001. Cutoff point &amp;gt;270 with sensitivity= 80% and specificity=73.3%. In Septic Shock Cases, ROC curve analysis proved good discriminating power of the Serum RAGE between Non Survivor group and Survivor group where Area under the ROC curve (AUC) = 0.955 with (95% Confidence interval 0.76–0.99); p &amp;lt; 0.001. Cutoff point &amp;gt;310.9 with sensitivity= 90% and specificity=91%. Conclusion Our study suggests that sRAGE may serve as a valuable biomarker for assessing the severity and prognosis of sepsis and septic shock in pediatric patients, although further research with a larger sample size is warranted to validate these findings.