Reliable Prognostic Indicator Research Articles

Global longitudinal strain correlates poorly with mortality in people with diabetes mellitus and receiving haemodialysis.

Haemodialysis (HD) is a life-sustaining treatment for individuals with end-stage kidney disease (ESKD). However, the risk of mortality remains significantly higher compared to the general population, even when matched for age and sex. Global longitudinal strain (GLS), derived from speckle tracking echocardiography, has shown promise as a predictor of mortality in HD patients. However, its prognostic utility in patients with multiple cardiovascular risk factors such as diabetes mellitus (DM) and receiving HD, remains unclear. This study aimed to evaluate the prognostic value of GLS in HD patients, with and without DM. This prospective study was a long term follow up extension study of an earlier published study that investigated a cohort of haemodialysis patients from a single centre with a comprehensive cardiovascular imaging protocol. All patients had an echocardiography with the use of speckle-tracking software to determine GLS. Patients were divided into Group A (with DM) and Group B (without DM). Patients were followed up until death, major adverse cardiovascular events (MACE), transplantation or the censoring date (29 February 2024). Statistical analyses were performed using univariate Cox proportional hazards models. A total of 184 patients receiving HD were included in the analysis. Patients with DM (Group A) had significantly higher all-cause mortality (ACM) (47.1% vs. 20.7%, P<0.001) and a lower chance of receiving a kidney transplant (13.2% vs. 43.1%, P<0.001). In Group A, GLS did not predict ACM, whereas in Group B, a GLS cutoff of -15.76% correlated with higher 5-year ACM (P=0.036). Left ventricular ejection fraction (LVEF) was a significant predictor of ACM in Group A (HR 0.98; P=0.036). GLS is a poor predictor of adverse outcomes in HD patients with DM, likely due to their high cardiovascular risk. In contrast, GLS was a significant predictor of mortality in non-diabetic HD patients. LVEF may be a more reliable prognostic indicator in high-risk diabetic patients.

Tumor-Infiltrating B Cells and Tissue-Resident Memory T Cells as Prognostic Indicators in Brain Metastases Derived from Gastrointestinal Cancers.

Tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) play significant roles in antitumor immunity. However, their prognostic relevance in brain metastases (BMs) derived from gastrointestinal (GI) cancers remains unclear. This study aimed to investigate the prognostic significance of TIBs and TRMs in GI cancer-derived BMs (GIBMs). Retrospective histopathological analyses were performed on surgically resected GIBM tissues from 13 patients. The densities of tumor-infiltrating lymphocytes (TIL) subsets (TIBs, CD4+ T cells, CD8+CD103+ TRMs, and CD8+CD103- non-TRMs) were quantified and correlated with clinical parameters and overall survival (OS) including the Graded Prognostic Assessment (GPA). TIBs and CD4+ T cells were predominantly accumulated in the tumor stroma, particularly around blood vessels, where they formed lymphocyte clusters without characteristics of tertiary lymphoid structures (TLSs). In contrast, TRMs more deeply infiltrated into the tumor epithelium than their counterpart non-TRMs. Positive correlations were found between TIB density and both the prognostic prediction of GPA and overall survival (OS) after BM diagnosis or surgery. Furthermore, increased densities of TIBs and TRMs were associated with enhanced survival after BM diagnosis. TIB and TRM densities in BM tissues could serve as reliable prognostic indicators for survival in patients with GIBMs. This study provides crucial insights for the development of novel immunotherapeutic strategies against this lethal disease.

Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.

Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) scores can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who are middle-aged and older remains unknown. This retrospective cohort study included 3566 individuals from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, and cardiovascular disease were conducted. After the follow-up was terminated, 920 participants experienced all-cause mortality, and 2646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality (hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.83-0.95). The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR = 1.46, 95% CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups. This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.

Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker.

As one of the malignant tumors with the highest incidence and fatality in the world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which has not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cell cycle, apoptosis, DNA damage repair, and other processes by changing the activity of substrate proteins or causing ubiquitin-proteasome degradation. These are the key links in the pathogenesis of COAD, and ubiquitin plays an important role in the occurrence and development of COAD. We integrated transcriptomics, single-cell and clinical omics, and TCGA and GEO databases of COAD patient data. Cox and Lasso regression was employed to assess ubiquitination genes in COAD for generating ubiquitination-related features. The aim was to evaluate the prognostic value of these features for tumors and their impact on the immune microenvironment. At the same time, the expression level of model genes was further analyzed using single-cell data. Finally, the expression and function of ASNS, a key gene for this trait, were detected in vitro. In our study, based on identifiable changes in the expression of marker genes, this feature can be used to classify patients with COAD. Kaplan-Meier survival analysis indicated that those with elevated risk scores in each cohort experienced inferior outcomes. There is good validation in both the training queue and the validation queue. The results of the immune infiltration analysis showed that the immune infiltration rate was significantly increased in the high-risk group. After the knockdown of ASNS, an important gene in the signature, the activity and migration capacity of SW620 and RKO cell lines and colony formation capacity were dramatically reduced in cell tests. We screened ubiquitination-related genes and constructed ubiquitination-related features, which can be used as reliable prognostic indicators of COAD. ASNS was identified as a possible biomarker for COAD.

Bioinformatics analysis reveals SOD1 is a prognostic factor in lung adenocarcinoma.

Lung cancer is a major cause of cancer-related deaths worldwide. Unfortunately, non-small cell lung cancer (NSCLC) often lacks clear clinical symptoms and molecular markers for early diagnosis, which can hinder the initiation of timely treatments. In this study, we conducted an extensive bioinformatics analysis of copper-zinc superoxide dismutase (SOD1), a molecule linked to lung adenocarcinoma (LUAD) to enhance early detection and treatment approaches for this condition. A bioinformatics analysis was conducted using a dataset from The Cancer Genome Atlas (TCGA) database. Several analytical methods, such as a differential expression analysis, a Kaplan-Meier survival analysis, a clinicopathological analysis, an enrichment analysis, protein-protein interaction (PPI) network construction using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and an immunoreactivity analysis of SOD1 expression in LUAD using TIMER were employed. We further validated the expression of SOD1 in LUAD through in vitro experiments using quantitative polymerase chain reaction (qPCR) and Western blot. Our findings indicate that LUAD tissues exhibited significantly higher expression levels of SOD1 than healthy tissues. The univariate Cox analysis showed that the elevated level was linked to unfavorable overall survival (OS) rates. Further, the Cox regression analysis of multiple variables suggested that elevated SOD1 expression levels acted as an autonomous prognosticator for unfavorable OS. We also conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and a gene set enrichment analysis (GSEA) and observed differential pathway enrichment among patients with high SOD1 expression. In addition, a correlation between SOD1 and immune cell infiltration was found. The in vitro experiments confirmed that SOD1 expression was upregulated in LUAD. SOD1 could serve as a reliable prognostic indicator in individuals diagnosed with LUAD. Our findings may prove valuable in the development of therapeutic and prognostic markers for LUAD. The potential clinical utility of SOD1 in LUAD requires further investigation.

Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation.

Gastric cancer is a kind of malignant tumor which is prevalent all over the world. Although some progress has been made in the treatment of gastric cancer, its prognosis is still not optimistic, so it is of great significance to find reliable prognostic indicators to guide the treatment and management of patients with gastric cancer. To explore the relationship between serum levels of five biomarkers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA72-4, CA24-2, and ferritin] and prognosis in patients with gastric cancer. This study included 200 patients with gastric adenocarcinoma, and conducted an in-depth analysis of their baseline characteristics, relationship between tumor markers and staging, and prognosis. The study found that CA19-9 has a significant correlation with tumor stage, the average levels of CA24-2, CEA, CA72-4 and ferritin were slightly increased disregarding the stage of tumor. Survival analysis showed that increases in CEA, CA19-9, CA24-2, and ferritin were all associated with shortened overall survival of patients. Further multivariate analysis revealed that elevated serum CA72-4 levels were an independent adverse prognostic factor. This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA, CA19-9, CA72-4, CA24-2 and ferritin in patients with gastric cancer and prognosis, and can be used as important indicators for prognostic evaluation of gastric cancer. In particular, markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis. Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer, and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

Claudin-9 (CLDN9) promotes gastric cancer progression by enhancing the glycolysis pathway and facilitating PD-L1 lactylation to suppress CD8+ T cell anti-tumor immunity

BackgroundGastric cancer (GC) is a common malignancy characterized by the absence of reliable prognostic indicators and effective therapeutic targets. Claudin-9 (CLDN9) has been demonstrated to be upregulated in various cancers. However, its prognostic value, biological function, and regulatory mechanisms in GC remain unclear. Therefore, this study aimed to elucidate the role of CLDN9 in GC progression and its underlying mechanisms. MethodsWe utilized consensus cluster, random survival forest, and multivariate Cox regression analyses to identify CLDN9 in GC. Subsequently, we evaluated the mRNA and protein levels of CLDN9 in GC using quantitative real-time polymerase chain reaction (PCR) (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC). Furthermore, the role of CLDN9 in GC progression was investigated using a series of functional in vivo and in vitro experiments. Finally, we elucidated the molecular mechanisms of CLDN9 using bioinformatics, molecular biology, animal models, and patient tissue specimens. ResultsTwo GC subtypes with survival and functional differences were identified based on glycolytic metabolic genes in the Cancer Genome Atlas (TCGA)- Stomach adenocarcinoma (STAD) dataset. A prognostic risk score was calculated using seven genes to assess the overall survival (OS) in GC. Using random survival forest and multivariate Cox analyses, we identified CLDN9 as the key gene linked to the glycolytic subtype and prognosis of GC. CLDN9 expression was significantly upregulated in patients with GC as well as in GC cells. CLDN9 knockdown inhibited tumor proliferation, invasion, and metastasis both in vivo and in vitro. Mechanistically, CLDN9 was found to regulate lactate dehydrogenase A (LDHA) expression and promote glycolytic metabolism by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF1α) signaling pathway. Additionally, lactate, a glycolytic metabolite, enhanced programmed cell death ligand 1 (PD-L1) lactylation and stability, which suppressed anti-tumor immunity in CD8+ T cells, thereby contributing to GC progression. ConclusionsCLDN9 expression is associated with GC development and progression. Mechanistically, CLDN9 enhances the glycolysis pathway and facilitates PD-L1 lactylation through the PI3K/AKT/HIF1α signaling pathway, thereby suppressing anti-tumor immunity in CD8+ T cells. CLDN9 has the potential to serve as a novel prognostic marker and therapeutic target for GC.

A Review of the Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Nonhematologic Malignancies.

Biomarkers are crucial in cancer diagnostics, prognosis, and surveillance. Extensive research has been dedicated to identifying biomarkers that are broadly applicable across multiple cancer types and can be easily obtained from routine investigations such as blood cell counts. One such biomarker, the neutrophil-to-lymphocyte ratio (NLR), has been established as a prognostic marker in cancer. However, due to the dynamic nature of cancer diagnosis and treatment, periodic updates are necessary to keep abreast of the vast amount of published data. In this review, we searched the PubMed database and analyzed and synthesized recent literature (2018-February 2024) on the role of NLR in predicting clinical outcomes in nonhematologic malignancies. The search was conducted using the PubMed database. We included a total of 88 studies, encompassing 28,050 human subjects, and categorized the findings into four major groups: gastrointestinal cancer, cancers of the urinary tract and reproductive system, lung cancer, and breast cancer. Our analysis confirms that NLR is a reliable prognostic indicator in cancer, and we discuss the specific characteristics, limitations, and exceptions associated with its use. The review concludes with a concise Q&A section, presenting the most relevant take-home messages in response to five key practical questions on this topic.

Cluster of Differentiation Markers and Human Leukocyte Antigen Expression in Chronic Lymphocytic Leukemia Patients: Correlations and Clinical Relevance.

Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD79b, CD45, CD23, CD22 and CD81 serve as reliable prognostic indicators in CLL as well as the human leukocyte antigen (HLA) with its well-documented associations with various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Although it is one of the most prevalent neoplasms, there is a need for biomarkers that can improve survival. This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing was performed for HLA typing. The results indicate that several CD markers are statistically associated with different HLA alleles, specifically CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01. In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

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.

The Respiratory Rate, Age, and Mean Arterial Pressure (RAM) Index: A Novel Prognostic Tool to Predict Mortality among Adult Patients with Acute Heart Failure in the Emergency Department.

Background and Objectives: Acute heart failure (AHF) is a life-threatening condition frequently encountered in the emergency department (ED). Identifying reliable prognostic indicators for in-hospital mortality is crucial for risk stratification and the appropriate management of AHF patients. This study aimed to assess the most effective method for predicting in-hospital mortality among various physiological parameters in patients with AHF presenting to the ED. Additionally, the study evaluated the effectiveness of the RAM index-respiratory rate (RR), age, and mean arterial pressure (MAP)-derived from the shock index (SI) by replacing heart rate with RR, as a novel prognostic tool. This was compared with the SI and its other derivatives to predict in-hospital mortality in adult patients with AHF presenting to the ED. Materials and Methods: This is a retrospective study conducted in the ED of an urban medical center, enrolling adult patients with signs and symptoms of AHF, who met the epidemiological diagnosis criteria, between January 2017 and December 2021. Baseline physiological parameters, including the RR, heart rate, systolic blood pressure, and diastolic blood pressure, were recorded upon ED admission. The RAM index was calculated as the RR multiplied by the age divided by the MAP. Statistical analysis was performed, including univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis. Results: A total of 2333 patients were included in the study. A RAM index > 18.6 (area under ROC curve (AUROC): 0.81; 95% confidence interval (CI): 0.79-0.83) had a superior mortality discrimination ability compared to an SI > 0.77 (AUROC: 0.75; 95% CI: 0.72-0.77), modified shock index > 1.11 (AUROC: 0.75; 95% CI: 0.73-0.77), age shock index > 62.7 (AUROC: 0.74; 95% CI: 0.72-0.76), and age-modified shock index > 79.9 (AUROC: 0.75; 95% CI: 0.73-0.77). A RAM index > 18.6 demonstrated a 7.36-fold higher risk of in-hospital mortality with a sensitivity of 0.80, specificity of 0.68, and negative predictive value of 0.97. Conclusions: The RAM index is an effective tool to predict mortality in AHF patients presenting to the ED. Its superior performance compared to traditional SI-based parameters suggests that the RAM index can aid in risk stratification and the early identification of high-risk patients, facilitating timely and aggressive treatment strategies.

Prognostic factors for tube feeding in type I SMA patients treated with disease-modifying therapies: a cohort study

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher’s exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline.What is Known:• The advent of disease-modifying therapies is increasingly changing the approach to swallowing and nutritional management in type I SMA.• Clinical trials and real-world data using all three disease-modifying therapies report a rather wide variability of feeding outcome and need for tube feeding that is often related to different cohorts that makes comparison between studies very difficult.What is New:• The real-world findings of this study, including all the children treated since treatments became available, confirmed that the need for tube feeding is not an invariable finding.• The level of feeding involvement at baseline appears to be a reliable prognostic indicator of bulbar outcome.• The results highlight the need for interventional studies with structured Speech and Language Therapist protocols that will help to better understand the extent to which bulbar function can be maintained or regained even in children requiring tube feeding.

Reirradiation in head and neck squamous cell carcinoma; prognostic indicators, oncologic and functional outcomes

ObjectivesPatients with recurrent squamous cell carcinoma of the head and neck (HNSCC) have a poor prognosis and limited therapeutic alternatives. While reirradiation is feasible, it is usually associated with high treatment toxicity and is not yet considered the standard of care. Based on current NCCN guidelines, in the context of very advanced head and neck cancer (recurrent and/or persistent disease), surgical intervention is explored initially with/without adjuvants while unresectable disease is approached with radiation and/or systemic therapies. Specific and reliable prognostic indicators for both -oncologic and functional outcomes- have yet to be defined for this population. MethodsRetrospective chart review of 54 patients treated with reirradiation at a tertiary academic institution between January of 1998 and January of 2024. Only patients with non-metastatic recurrent, and second primary HNSCC were included in the series. Demographics, staging, radiation dose and technique, additional therapy, histopathologic variables, EORTC toxicity, pre- and post-treatment PEG/tracheotomy dependency and oncologic outcomes were retrieved. ResultsThe study cohort consisted of 54 patients (37 males, 17 females) with HNSCC, averaging 62.7 years in age. Initial tumors were locally advanced in over 42 % of cases, with 58 % being node-negative. The head and cutaneous regions (24.5 %) and tongue (20.8 %) were the most common tumor sites. Primary surgical resection and adjuvant radiation were performed in 47.2 % of cases, and concurrent chemotherapy was used in 40.7 %. Reirradiation was mainly for local or regional recurrence (88.9 %), often following salvage surgery (68.5 %), with a mean dose of 5623 Gy over 52.5 fractions. Positive surgical margins were present in 29.4 % of cases, and extracapsular spread in 59.5 %. No significant differences were found between the salvage surgery and definitive reirradiation groups except for tumor site (P = 0.022). Median follow-up was 52.6 months, with 27 deaths reported. Lymphovascular invasion was significantly correlated with overall survival (P = 0.017), while initial tumor T-stage and neck disease involvement were linked to local-regional control (P = 0.030 and P = 0.033, respectively). Reirradiation increased tracheotomy and PEG-tube dependency by 20 % (P = 0.011) and 23 % (P = 0.003), respectively. ConclusionsReirradiation is a feasible therapeutic alternative in recurrent head and neck SCC. Oncologic outcomes observed in this series compare favorably to most published reports. Complete response and perineural invasion were independent prognostic factors for survival and locoregional control. While no mortality directly associated with treatment was observed in this series, reirradiation had a significant impact in functional outcomes in terms of increased risk of tracheotomy and peg tube dependency. Further studies are required to define the role of this treatment in head and neck cancer.

Prognostic significance of exportin-5 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies. To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker. This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5's impact on immune cell infiltration and validated its prognostic potential using machine learning. XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set. Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.

Prognostic value of brachial-ankle pulse wave velocity changes post-transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) offers a solution, especially for high-risk aortic stenosis (AS) patients. However, patient outcomes post-TAVR show variability, highlighting the need for reliable prognostic indicators. Brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, may predict outcomes post-TAVR. This study aims to explore baPWV's prognostic value in relation to all-cause mortality post-TAVR. This study prospectively enrolled 212 severe AS patients undergoing TAVR between September 2015 and December 2021, focusing on pre- and post-TAVR baPWV measurements to explore associations with all-cause mortality. Of the 212 patients (119 females, 93 males, mean age 85years), post-TAVR baPWV increased significantly from 1589 ± 376 to 2010 ± 521cm/s (p < 0.001). Aortic valve (AV) peak velocity and mean pressure gradient decreased, while AV area increased, indicating procedural success. Despite this, 88% of patients experienced an increase in baPWV, with higher pre-procedure AV peak velocity and mean pressure gradient identified as predictors of increased baPWV post-TAVR. Over 23months, 29 patients (14%) reached the primary endpoint of all-cause mortality. Notably, changes in baPWV, rather than baseline values, were significantly associated with event-free survival (HR: 0.64 per 1SD increase, p = 0.009). The study highlights the prognostic value of baPWV changes post-TAVR in predicting patient outcomes. Elevated baPWV post-TAVR may reflect a beneficial adaptation to altered hemodynamics, suggesting the need for individualized patient evaluation and the integration of baPWV measurements into clinical practice for improved post-TAVR management.

Mitotic catastrophe heterogeneity: implications for prognosis and immunotherapy in hepatocellular carcinoma.

The mitotic catastrophe (MC) pathway plays an important role in hepatocellular carcinoma (HCC) progression and tumor microenvironment (TME) regulation. However, the mechanisms linking MC heterogeneity to immune evasion and treatment response remain unclear. Based on 94 previously published highly correlated genes for MC, HCC patients' data from the Cancer Genome Atlas (TCGA) and changes in immune signatures and prognostic stratification were studied. Time and spatial-specific differences for MCGs were assessed by single-cell RNA sequencing and spatial transcriptome (ST) analysis. Multiple external databases (GEO, ICGC) were employed to construct an MC-related riskscore model. Identification of two MC-related subtypes in HCC patients from TCGA, with clear differences in immune signatures and prognostic risk stratification. Spatial mapping further associates low MC tumor regions with significant immune escape-related signaling. Nomogram combining MC riskscore and traditional indicators was validated great effect for early prediction of HCC patient outcomes. MC heterogeneity enables immune escape and therapy resistance in HCC. The MC gene signature serves as a reliable prognostic indicator for liver cancer. By revealing clear immune and spatial heterogeneity of HCC, our integrated approach provides contextual therapeutic strategies for optimal clinical decision-making.

Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients

BackgroundOver the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed.MethodsRNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm.ResultsData obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts.ConclusionWe identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.

Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes

AimThis study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). MethodsData from 10,035 NAFLD patients identified within the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). ResultsNPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19–1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. ConclusionsThis study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.

Prognostic and clinicopathological value of Ki-67 in patients with oesophageal squamous cell carcinoma: a systematic review and meta-analysis

ObjectivesThe relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was...

Predicting prostate adenocarcinoma patients’ survival and immune signature: a novel risk model based on telomere-related genes

Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan–Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.