Prognostic Biomarker In Patients Research Articles

Excessive daytime sleepiness, morning tiredness, loud snoring, and prognostic biomarkers in patients with chronic coronary syndrome

Abstract Background Sleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established. Methods Associations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-relatedsymptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring [LS]; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac Troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A2 activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models with never/rarely as reference. Results EDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03-1.10], always 1.15 [1.10-1.21]), GDF-15 (often 1.03 [1.01-1.06], always 1.07 [1.03-1.11]), NT-proBNP (always 1.22 [1.12-1.33]), and hs-cTnT (always 1.07 [1.01-1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01-1.09], always 1.09 [1.04-1.15]), and GDF-15 (always 1.06 [1.03-1.10]). LS was associated with decreased levels of NT-proBNP (sometimes 0.94 [0.90-0.98], often 0.92 [0.87-0.97], always 0.87 [0.81-0.92]), and hs-cTnT (always 0.94 [0.91-0.98]). Conclusions In patients with CCS, gradually increased frequency of SRBD-related symptoms, such as EDS, MT, and LS, were independently and consistently associated with varying levels of IL-6, GDF-15, and NT-proBNP, each reflecting distinct pathophysiological pathways or underlying pathology of cardiovascular disease. Figure 1. Adjusted analysis of associations between sleep-related breathing disorder-related questions and geometric mean ratios of prognostic biomarkersFigure 1A.Excessive Daytime SleepinessFigure 1B.Loud Snoring

Novel miRNAs are key predictors of heart failure and mortality in functional tricuspid regurgitation

Abstract Background Functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, in particular heart failure (HF), but optimal timing for intervention remains controversial. Surgery is often performed late mainly because symptoms might go unnoticed until advance stage of the disease. While microRNA have been recently identified as prognostic biomarkers in different cardiovascular conditions, no study has been focus on patients with TR. Purpose To evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients with severe FTR. Methods Consecutive patients with severe FTR evaluated in the Heart Valve Clinic were prospectively included and underwent a comprehensive clinical protocol. Patients with non-valvular permanent atrial fibrillation (and no TR) undergoing anticoagulant therapy unit were prospectively recruited as a control group. The experimental design included a first screening phase in 16 subjects (8 atrial FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 118 additional patients (77 FTR and 41 controls). A combined endpoint of hospital admission due to HF and all-cause mortality at follow-up was defined. Results The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjects matched by age, gender and atrial dimensions. The candidate miRNAs were subsequently validated in 118 subjects. After a median follow up of 20.4 months (ICR 8-35 months), 25 (32%) reached the combined endpoint. Patients with events showed different levels of miR-15a-5p, miR-152-3p, miR101-3p, miR-92a-3p, miR-363-3p, miR-324-3p and miR-22-3p (Table 1, p<0.05 for all). Based on the high or low relative expression of selected miRNAs (below or above the median value) patients were stratified; those patients with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p and miR-22-3p, showed significantly higher rates of events (log rank test for all p < 0.01, figure). In a multivariate cox regression the analysis, the level of miR-15a-5p (HR: 3.97 [1.58-9.96], miR-92a-3p (HR: 2.64 [1.13-6.13] , and miR-363-3p (HR: 2.41 [1.04-5.60] were predictive of events independently of NYHA functional class and RV dimensions (p < 0.05 for all). Conclusions We identify for the first time circulating miRNAs in patients with severe FTR. We further show that several miRNA predict heart failure and all-cause mortality independently of RV dimension and symptomatic status. These novel biomarkers may help to identify those patients that benefit from earlier valve interventions.Differences in patients with eventsKaplan Meier Curves

Inhibition of the Cyclin K-CDK12 complex induces DNA damage and increases the effect of androgen deprivation therapy in prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay of the current first-line treatment concepts for patients with advanced prostate carcinoma (PCa). However, due to treatment failure and recurrence investigation of new targeted therapeutics is urgently needed. In this study, we investigated the suitability of the Cyclin K-CDK12 complex as a novel therapeutic approach in PCa using the new covalent CDK12/13 inhibitor THZ531. Here we show that THZ531 impairs cellular proliferation, induces apoptosis, and decreases the expression of selected DNA repair genes in PCa cell lines, which is associated with an increasing extent of DNA damage. Furthermore, combination of THZ531 and ADT leads to an increase in these anti-tumoral effects in androgen-sensitive PCa cells. The anti-proliferative and pro-apoptotic activity of THZ531 in combination with ADT was validated in an ex vivo PCa tissue culture model. In a retrospective immunohistochemical analysis of 300 clinical tissue samples we show that Cyclin K (CycK) but not CDK12 expression correlates with a more aggressive type of PCa. In conclusion, this study demonstrates the clinical relevance of the CycK-CDK12 complex as a promising target for combinational therapy with ADT in PCa and its importance as a prognostic biomarker for patients with PCa.

Interleukin-6 and Epidermal Growth Factor as non-invasive biomarkers of progression in chronic glomerulonephritis.

Several cytokines and chemokines are involved in the pathogenesis and progressive injury of renal tissues in patients with primary chronic glomerulonephritis (CGN). The objective of this study was to determine whether the urinary excretion of interleukin-6 (IL-6), transforming growth factor β1 (TGFβ1), monocytes chemoattractant protein (MCP-1), soluble tumor necrosis factor receptor 1 (sTNFR1) and epidermal growth factor (EGF) in patients with newly recognized CGN can serve as prognostic biomarkers in patients with newly recognized CGN and whether they can be effective in predicting a progressive reduction of renal function in prospective observation. The study included 150 Caucasian patients. UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 and UEGF were measured using ELISA methods (Quantikine R&D System). UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 were significantly higher, yet UEGF excretion was significantly lower in nephrotic patients, in patients with estimated glomerular filtration rate (eGFR) < 60/min/1,73m2 at presentation, as well as in the progressor (PG) subgroup. In a multivariate regression analysis basal eGFR correlated with UsTNFR1, UIL-6 and UEGF excretion, although in the follow-up, ΔeGFR (delta estimated glomerular filtration rate) significantly correlated only with UEGF excretion. A logistic regression analysis showed that the most significant independent risk factors for the deterioration of renal function with time are initial high (>11.8 pg/mgCr) UIL-6 excretion, initial low (<15.5 ng/mgCr) urinary UEGF excretion and male gender. In patients with newly diagnosed CGN, UIL-6 and UEGF can serve as prognostic biomarkers for the progression of the disease.

Pretreatment Neutrophil-to-Lymphocyte Ratio as Prognostic Biomarkers in Patients with Unresectable Hepatocellular Carcinoma Treated with Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups. Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR<3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102-4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128-4.764; p = 0.022), and NLR ≥3.46 (HR, 2.35; 95% CI, 1.239-4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS. NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.

Galectin-3 as a Prognostic Biomarker in Patients with First Acute Myocardial Infarction without Heart Failure.

Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and quality of life. Our study included 59 patients with AMI and a preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 h of chest pain onset from the aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACEs) were evaluated at six months follow-up. MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from the aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p = 0.038; OR 3.438; 95%CI: 1.275-9.265; p = 0.015). ROC analysis identifies the Gal-3 plasma concentration from the aortic root as a better predictor of MACE or death (cut-off ≥ 10.86 ng/mL; AUC 0.858; 95%CI: 0.744-0.973; p < 0.001) than Gal-3 plasma concentration from the femoral/radial artery (cut-off ≥ 10.18 ng/mL; AUC 0.742; 95%CI: 0.596-0.888; p = 0.006). the Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 h after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Panax quinquefolium saponins attenuates microglia activation following acute cerebral ischemia-reperfusion injury via Nrf2/miR-103-3p/TANK pathway.

Ischemic stroke is one of the leading causes of death and disability among adults worldwide. Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. However, reperfusion by thrombolysis will lead to the rapid activation of microglia cells which induces interferon-inflammatory response in the ischemic brain tissues. Panax quinquefolium saponins (PQS) has been proven to be effective in acute ischemic stroke, but there is no unified understanding about its specific mechanism. Here, we will report for the first time that PQS can significantly inhibit the activation of microglia cells in cerebral of MCAO rats via activation of Nrf2/miR-103-3p/TANKaxis. Our results showed that PQS can directly bind to Nrf2 protein and inhibit its ubiquitination, which result in the indirectly enhancing the expression of TANK protein via transcriptional regulation on miR-103-3p, and finally to suppress the nuclear factor kappa-B dominated rapid activation of microglial cells induced by oxygen-glucose deprivation/reoxygenationvitro and cerebral ischemia-reperfusion injury in vivo. In conclusion, our study not only revealed the new mechanism of PQS in protecting against the inflammatory activation of microglia cells caused by cerebral ischemia-reperfusion injury, but also suggested that Nrf2 is a potential target for development of new drugs of ischemic stroke. More importantly, our study also reminded that miR-103-3p might be used as a prognostic biomarker for patients with ischemic stroke.

IGF2BP2 promotes head and neck squamous carcinoma cell proliferation and growth via the miR-98-5p/PI3K/Akt signaling pathway.

As a N6-methyladenosine reader protein, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a critical player in tumor progression and metastasis. However, its specific function in head and neck squamous carcinoma (HNSCC) has yet to be determined. The present study aimed to determine the role of IGF2BP2 in HNSCC. The expression of IGF2BP2 in HNSCC was analyzed using The Cancer Genome Atlas (TCGA) dataset and detected in HNSCC tissues and cells, respectively. Gain- and loss- of function methods were employed to study the effects of IGF2BP2 on HNSCC cell proliferation and tumorigenesis in vitro and in vivo. MicroRNAs (miRNAs) regulating IGF2BP2 were predicted using online tools and confirmed experimentally. We showed augmented IGF2BP2 expression in HNSCC, which correlated with poor clinical outcomes. Functional studies showed that IGF2BP2 promoted HNSCC cell proliferation by facilitating cell cycle progression while inhibiting apoptosis. We further demonstrated that IGF2BP2 could enhance HNSCC cell tumorigenesis in vivo. Mechanistically, our data revealed that miR-98-5p could directly target IGF2BP2. The interplay between IGF2BP2 and miR-98-5p is essential to drive the progression of HNSCC via the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) pathway signaling pathway. The current study revealed the oncogenic role of IGF2BP2 and provided insights into its potential mechanism in HNSCC tumorigenesis. Additionally, IGF2BP2 might represent a promising therapeutic target and serve as prognostic biomarker in patients with HNSCC.

Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients.

This study attempted to identify exosomal circular RNAs (circRNAs) as diagnostic and prognostic biomarkers for patients with ST-segment elevation myocardial infarction (STEMI). The differentially expressed exosomal circRNAs (DEECs) were screened from microarray dataset (GSE160717 and GSE197137) and RNA-Seq dataset (GSE208194), and the expression levels of DEECs in patients with STEMI were validated using reverse transcription and quantitative real-time PCR. The diagnostic value of DEECs was assessed using receiver operating characteristic curves. The major adverse cardiovascular event (MACE)-free 1-year survival rate was evaluated using the Kaplan-Meier method, and the factors affecting prognosis were determined using Cox regression model analysis. Results showed that four DEECs were screened including exo-circ-0001490, exo-circ-0020887, exo-circ-0009590, and exo-circ-0055440, and only upregulated exo-circ-0020887 and exo-circ-0009590 expression was validated in patients with STEMI. The exo-circ-0020887 and exo-circ-0009590 expression was positively correlated with hs-CRP, LDL-C, cTnI, and CK-MB. The exo-circ-0020887 and exo-circ-0009590 showed good diagnostic efficacy to distinguish STEMI patients from healthy controls (area under the curves: 0.85 and 0.80). STEMI patients with high levels of exo-circ-0020887 and exo-circ-0009590 had lower MACE-free 1-year survival rate, and exo-circ-0020887 and exo-circ-0009590 expression was independent risk factors for adverse prognosis. In summary, upregulation of plasma exo-circ-0020887 and exo-circ-0009590 might act as potential biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in patients with STEMI.

Association Between C-Reactive Protein and Albumin Ratios and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease.

This study was to evaluate the association between C-reactive protein (CRP) to albumin (ALB) ratio (CAR) and the risk of mortality in patients with chronic obstructive pulmonary disease (COPD). In this retrospective cohort study, clinical data were extracted from the National Institutes of Health National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2010. Cox proportional hazard regressions were performed to assess the association between CAR and 5-year mortality in COPD patients. Subgroup analyses were applied to identify the consistency of the association based on the severity of COPD, gender, body mass index (BMI), smoking status, cardiovascular disease (CVD), and chronic kidney disease (CKD), and diabetes. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive performance of CAR. A total of 1210 COPD patients were included, of which 110 COPD patients (9.09%) had 5-year mortality. The mean follow-up was 57.76 (0.33) months. A higher CAR was associated with an increased risk of 5-year mortality in COPD patients [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.07 to 3.50, P =0.029)]. Subgroup analysis showed that the association between CAR and mortality was especially suitable for COPD patients with mild COPD, in COPD patients who were still smoking, in COPD patients with BMI <=29.9 kg/m2, in COPD patients who were without CVD, in COPD patients who were without diabetes, and COPD patients who were without CKD. The AUCs of CAR for predicting 1-year, 3-year, and 5-year mortality in COPD patients were 0.735, 0.615, and 0.608, respectively. CAR is strongly correlated with mortality in patients with COPD and CAR could be served as a prognostic biomarker for patients with COPD. This study may provide a promising prognostic biomarker for risk stratification and clinical management of patients with COPD.

Expression and Prognostic Significance of Ferroptosis-related Proteins SLC7A11 and GPX4 in Renal Cell Carcinoma.

The ferroptosis inhibitory gene solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) inhibit ferroptosis in carcinoma cells. However, whether SLC7A11 and GPX4 serve as an oncogene in renal cell carcinoma (RCC) remains unclear. Immunohistochemistry (IHC) assays were performed to assess the expression of SLC7A11 and GPX4 in human RCC tissues. Clinical-pathological analysis was performed to explore the correlation between SLC7A11 and GPX4 expression. Kaplan-Meier survival analysis was performed to characterise the associations between protein expression and patient progressionfree survival (PFS). The upregulation of SLC7A11 and GPX4 was detected by IHC in RCC tissues compared with that in normal renal tissues. Meanwhile, the expression level of SLC7A11 and GPX4 was correlated with tumour diameter and distant metastasis (P<0.05). Kaplan-Meier survival analysis indicated that patients with high SLC7A11 and GPX4 expression levels exhibited worse PFS than those with low SLC7A11 and GPX4 expression levels (P<0.05). The upregulation of SLC7A11 and GPX4 expression was associated with poor prognosis in patients with RCC. SLC7A11 and GPX4 may serve as diagnostic and prognostic biomarkers for patients with RCC.

558MO Circulating tumor (ct)DNA as a prognostic biomarker in patients (pts) with resected colorectal cancer (CRC): An updated 24 months (mos) disease free survival (DFS) analysis from GALAXY study (CIRCULATE-Japan)

558MO Circulating tumor (ct)DNA as a prognostic biomarker in patients (pts) with resected colorectal cancer (CRC): An updated 24 months (mos) disease free survival (DFS) analysis from GALAXY study (CIRCULATE-Japan)

The Warburg effect in patients with brain tumors: a comprehensive analysis of clinical significance.

The Warburg Effect, referring to an elevation in serum lactate level attributable to increased tumor metabolism, is present in patients with brain tumors. This study comprehensively analyzes the Warburg effect in patients undergoing brain tumor resection. We retrospectively analyzed the baseline intraoperative serum lactate levels of 2,053 patients who underwent craniotomies, including 415 with cerebral aneurysms and 1,638 with brain tumors. The brain tumor group was divided into subgroups based on the tumor pathology (extra-axial and intra-axial tumor) and the WHO tumor grade (high-grade and low-grade). Serum lactate level was significantly higher in the tumor group than in the aneurysm group (1.98 ± 0.97 vs. 1.09 ± 0.57 mmol/L, p < 0.001). The hyperlactatemia incidence (serum lactate level > 2.2 mmol/L) was higher in the tumor group (33.5 vs. 3.1%, p < 0.001). Severe hyperlactatemia (serum lactate level > 4.4 mmol/L) was found in 34 patients (2.1%) of only the tumor group. In patients with intra-axial tumors, serum lactate level was greater in high- than low-grade tumors (2.10 ± 1.05 vs. 1.88 ± 0.92 mmol/L, p = 0.006). Factors predictive of hyperlactatemia included supratentorial tumor location (odds ratio[95%CI] 2.926[2.127-4.025], p < 0.001) and a long tumor diameter (1.071[1.007-1.139], p = 0.028). In high-grade intra-axial brain tumor patients, there was a significant difference in overall survival between patients with hyperlactatemia than those without (p = 0.048). Our results show that brain tumor patients exhibit the Warburg effect and serum lactate may be a useful diagnostic and prognostic biomarker in patients with high-grade intra-axial brain tumors.

Prognostic significance of catestatin in patients with primary hypertension and type 2 diabetes mellitus

The aim of this study was to determine predictors of cardiovascular complications of arterial hypertension (AH) and type 2 diabetes mellitus (T2DM) and investigate the prognostic potential of catestatin (CST) and relaxin-2 (RLN-2) in this patient population. Materials and methods. The research was performed in accordance with all ethical principles of the Declaration of Helsinki. All study participants signed a written informed consent. This study involved 106 patients with primary hypertension and 30 healthy volunteers. 55 hypertensive patients had comorbid T2DM. Plasma CST and RLN-2 levels were measured by an enzyme-linked immunosorbent assay. Major adverse cardiovascular events (MACE) were collected during 12-month follow-up via telephone interviews at visits in months 3, 6, 9, and 12. The end points of this study were acute myocardial infarction, ischemic stroke, acute heart failure and cardiac death. Statistical data analysis was performed using the SPSS 25.0 statistical software. Results. 13 end-points were registered in patients with AH during the 12-month follow-up period, but the difference in frequency of MACE occurrence between patients with AH and T2DM and hypertensive patients without T2DM was insignificant (p=0.181). The Cox proportional hazard model indicated CST (p=0.01), but not RLN-2 (p=0.20), as an independent predictor of MACE in hypertensive patients. Age (p=0.01), AH duration (p=0.03), presence of T2DM (p=0.03), HOMA-IR index (p=0.02), insulin (p=0.02) and uric acid levels (p=0.02) were also established as independent factors of end-points occurrence. Conclusions. CST is an independent factor for predicting cardiovascular complications of AH, which allows us to consider it as a prognostic biomarker in patients with AH, especially hypertensive patients with comorbidity T2DM

Blink Reflex Examination in Patients with Amyotrophic Lateral Sclerosis Compared to Diseases Affecting the Peripheral Nervous System and Healthy Controls.

Amyotrophic lateral sclerosis (ALS) is a fatal form of neuromuscular disease. The aim of this study was to assess changes in the blink reflex (BR) parameters as a valid and easy-to-use tool in ALS patients. We assessed the BR test in patients with a definitive diagnosis of ALS, healthy volunteers, and patients with diseases affecting the peripheral nervous system. The BR was studied in 29 patients who met the Awaji criteria. Latencies were compared with our healthy controls (N = 50) and other diseases of the peripheral nervous system (N = 61). The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to evaluate functional status. Significantly prolonged R2i and R2c latencies were found in the ALS group compared with the healthy control group (p < 0.001). The latencies of R1, R2i, R2c were all increased in the bulbar subtype compared to the limb-onset subtype (p < 0.05). According to our results, BR examination might be a promising tool to monitor the course of the disease or serve as a prognostic biomarker in patients with ALS, but it should be assessed in further studies. The abnormalities detected through BR might help perform earlier interventions in ALS patients and might be useful in other diseases affecting the peripheral nervous system.

Excessive daytime sleepiness, morning tiredness, and prognostic biomarkers in patients with chronic coronary syndrome

BackgroundSleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established. MethodsAssociations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-related symptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A2 activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models testing for trends with the never/rarely category serving as reference. ResultsEDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03–1.10], always 1.15 [1.10–1.21]), GDF-15 (often 1.03 [1.01–1.06], always 1.07 [1.03–1.11]), NT-proBNP (always 1.22 [1.12–1.33]), and hs-cTnT (always 1.07 [1.01–1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01–1.09], always 1.09 [1.04–1.15]), and GDF-15 (always 1.06 [1.03–1.10]). All symptoms were to some degree associated with higher levels of hs-CRP and loud snoring was also associated with decreased levels of NT-proBNP and hs-cTnT. ConclusionsIn patients with CCS, stepwise increased frequency of SRBD-related symptoms, such as EDS and MT, were associated with gradually higher levels of IL-6 and GDF-15, each reflecting distinct pathophysiological pathways.

Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis

BackgroundNeoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). MethodsWe conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). ResultsTwelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2–4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2–24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62–84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86–3.30) and OS (HR 2.66, 95% CI 1.65–4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77–3.30). ConclusionsHigh Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer.

Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

Immunophenotyping characteristics and outcome of COVID-19 patients: peripheral blood CD8+T cell as a prognostic biomarker for patients with Nirmatrelvir.

Nirmatrelvir has been authorized for the treatment of both hospitalized and non-hospitalized COVID-19 patients. However, the association between T lymphocyte subsets and the outcome of hospitalized COVID-19 patients treated with oral Nirmatrelvir has not been investigated. The objective of this study was to examine whether lymphocyte subsets could serve as biomarkers to assess the risk of mortality in COVID-19 patients undergoing Nirmatrelvir treatment, with the aim of enhancing medication management for COVID-19 patients. We conducted a retrospective cohort study at the Xiangya Hospital of Central South University in China between December 5, 2022 and January 31, 2023. The study reported demographic, clinical, T lymphocyte subsets, and inflammatory cytokine data of COVID-19 patients. We evaluated the associations of T lymphocyte subsets on admission with the composite outcome or death of patients using univariate and multivariable Cox regression analyses with hazards ratios (HRs) and 95% confidence intervals (CIs). We identified 2118 hospitalized COVID-19 patients during the study period, and conducted a follow-up of up to 38 days. Of these, 131 patients received Nirmatrelvir, with 56 (42.7%) in the composite outcome group, and 75 (57.3%) in the non-composite outcome group. Additionally, 101 (77.1%) patients were discharged, while 30 (22.9%) died. Our results showed a significant decrease in the CD3+, CD4+, and CD8+ T cell counts of patients in the composite outcome group and mortality group compared to the non-composite outcome group and discharged group, respectively. Multivariate Cox regression analysis showed that the significant decrease in CD8+ T cell count in peripheral blood was independently associated with the composite outcome in COVID-19 patients treated with Nirmatrelvir, with an HR of 1.96 (95%CI: 1.01-3.80). The significant decrease in CD4+ and CD8+ T cell counts in peripheral blood increased the hazard of developing mortality, with HRs of 6.48 (95%CI: 1.47-28.63) and 3.75 (95%CI: 1.27-11.11), respectively. Our study revealed a significant positive correlation between a decrease in CD8+ T cell counts and progression and mortality of hospitalized COVID-19 patients treated with Nirmatrelvir. Lower counts (/μL) of CD8+ T cell (<201) were associated with a higher risk of in-hospital severity and death. Our findings may provide valuable references for physicians in optimizing the use of Nirmatrelvir.

An EMT-related genes signature as a prognostic biomarker for patients with endometrial cancer

BackgroundThe epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC.MethodsRNA sequencing profiles of EC patients obtained from The Cancer Genome Atlas (TCGA) database were used to screen differential expression genes (DEGs) between tumors and normal tissues. The Cox regression model with the LASSO method was utilized to identify survival-related DEGs and to establish a prognostic signature whose performance was evaluated by Kaplan–Meier curve, receiver operating characteristic (ROC) and calibration curve. Eventually, functional enrichment analysis and cellular experiments were performed to reveal the roles of prognosis-related genes in EC progression.ResultsA total of 540 EMT-related DEGs in EC were screened, and subsequently a four-gene risk signature comprising SIRT2, SIX1, CDKN2A and PGR was established to predict overall survival of EC. This risk signature could serve as a meaningfully independent indicator for EC prognosis via multivariate Cox regression (HR = 2.002, 95%CI = 1.433–2.798; P < 0.001). The nomogram integrating the risk signature and clinical characteristics exhibited robust validity and performance at predicting EC overall survival indicated by ROC and calibration curve. Functional enrichment analysis revealed that the EMT-related genes risk signature was associated with extracellular matrix organization, mesenchymal development and cellular component morphogenesis, suggesting its possible relevance to epithelial-mesenchymal transition and cancer progression. Functionally, we demonstrated that the silencing of SIX1, SIRT2 and CDKN2A expression could accelerate the migratory and invasive capacities of tumor cells, whereas the downregulation of PGR dramatically inhibited cancer cells migration and invasion.ConclusionsAltogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients.