Prognostic Biomarker In Patients Research Articles

Dickkopf-related protein 1 as a biomarker of local immune status and worse prognosis of Oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. To examine the role and effect of DKK1 in OSCC. The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4 + T cells were associated with improved 5-year survival rates. DKK1 is a prognostic biomarker for patients with OSCC.

The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma

DBF4 zinc finger (DBF4) is a critical component involved in DNA replication and cell proliferation. It acts as a positive regulator of the cell division cycle 7 kinase. In this study, our investigation encompassed the impact of DBF4 on hepatocellular carcinoma (HCC) progression and delved into the potential mechanisms. We utilized open-access databases like TCGA and GEO to analyze the association between DBF4 and 33 different tumor types. We also conducted immunohistochemistry experiments to validate the expression of DBF4 in HCC, STAD, COAD, READ, PAAD, and LGG. Furthermore, we employed lentiviral transduction to knockdown DBF4 in HLF and SMMC cells, as well as to overexpress DBF4 in Huh7 cells. Subsequently, we evaluated the impact of DBF4 on proliferation, migration, and invasion of hepatocellular carcinoma cells. RNA sequencing and KEGG pathway enrichment analysis were also conducted to identify potential pathways, which were further validated through WB experiments. Finally, pathway inhibitor was utilized in rescue experiments to confirm whether DBF4 exerts its effects on tumor cells via the implicated pathway. Our findings revealed that DBF4 exhibited significant expression levels in nearly all examined tumors, which were further substantiated by the results of immunohistochemistry analysis. High DBF4 expression was correlated with poor overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), disease-free interval (DFI), relapse-free interval (RFI) in majority of tumor types, particularly in patients with HCC. In vitro experiments demonstrated that inhibition of DBF4 impaired the proliferative, migratory, and invasive abilities of HCC cells, whereas overexpression of DBF4 promoted these phenotypes. Sequencing results indicated that DBF4 may induce these changes through the ERBB signaling pathway. Further experimental validation revealed that DBF4 activates the ERBB signaling pathway, leading to alterations in the JNK/STAT, MAPK, and PI3K/AKT signaling pathways, thereby impacting the proliferative, migratory, and invasive abilities of tumor cells. Lastly, treatment of Huh7 cells overexpressing DBF4 with the ERBB2 inhibitor dacomitinib demonstrated the ability of ERBB2 inhibition to reverse the promoting effect of DBF4 overexpression on the proliferative, migratory, and invasive abilities of HCC cells. DBF4 plays a pivotal oncogenic role in HCC by promoting the ERBB signaling pathway and activating its downstream PI3K/AKT, JNK/STAT3, and MAPK signaling pathways. DBF4 may serve as a prognostic biomarker for patients with HCC.

Association between immune-related adverse events and prognosis in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) provides a variety of options for patients with advanced non-small-cell lung cancer (NSCLC). After the application of ICIs, the immune system of patients was highly activated, and immune-related adverse events (irAEs) could occur in some organ systems, and irAEs seemed to be associated with the survival prognosis of patients. Therefore, we evaluated the association between survival outcomes and irAEs in NSCLC patients and conducted a systematic review and meta-analysis.MethodsWe conducted systematic reviews of PubMed, Embase, Cochrane, and Web of Science databases until December 2021. The forest map was constructed by combining the hazard ratio (HR) and 95% confidence interval (CI). I2 estimated the heterogeneity between studies. A meta-analysis was performed using R 4.2.1 software.ResultsEighteen studies included 4808 patients with advanced NSCLC. In pooled analysis, the occurrence of irAEs was found to be a favorable factor for improved prognosis (PFS: HR: 0.48, 95% CI: 0.41-0.55, P <0.01; OS: HR: 0.46, 95% CI: 0.42-0.52, P <0.01). In subgroup analyses, cutaneous irAE, gastrointestinal irAE, endocrine irAE and grade ≥3 irAEs were associated with improvements in PFS and OS, but pulmonary and hepatic irAEs were not.ConclusionExisting evidence suggests that the occurrence of irAEs may be a prognostic biomarker for advanced NSCLC. However, further research is needed to explore the prospect of irAEs as a prognostic biomarker in patients undergoing immunotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPEROFILES/405333_STRATEGY_20240502.pdf, identifier CRD42023405333.

Cell-free human papillomavirus (HPV) DNA is a sensitive biomarker for prognosis and for early detection of relapse in locally advanced cervical cancer.

Human papillomavirus (HPV) is the cause of the majority of cervical cancers and has been showed to be released as cell-free tumour DNA (ctHPV DNA) into the circulation. We here analyse if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC). 74 patients with LACC were included, 66/74 were positive for 13 high-risk HPV-types using a bead-based assay on tumour biopsies. HPV-type-specific droplet digital PCR (ddPCR) assays were developed. Longitudinal plasma samples were then analysed for the biopsy-verified HPV-type for each patient. 418 plasma samples were analysed. Patients were followed for a median of 37 months. Results were correlated to tumour- and clinical characteristics. 92.4% of pre-treatment plasma samples were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1-2 months after end-of-treatment) or tumour evaluation (3-4 months after end-of-treatment) plasma was correlated with worse progression-free survival (p < 0.001) compared to if ctHPV DNA was not found. The positive predictive value of ctHPV-status at early follow-up for predicting disease progression was 87.5% and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed on radiology in all patients (n=10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time. ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.

Circulating myostatin levels as a prognostic biomarker in patients with acute liver failure and late-onset hepatic failure.

Myostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late-onset hepatic failure (LOHF) are unclear. In this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme-linked immunosorbent assay. Myostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522pg/mL, controls: 3853pg/mL, p=0.003). The prevalence of low myostatin in deceased patients was significantly higher than that in spontaneous survivors and patients who underwent liver transplantation. Patients with low myostatin levels had a high incidence of complications. There was a positive correlation between the psoas muscle index and serum myostatin levels. Patients with low myostatin levels had shorter 1-year transplant-free survival and shorter 1-year overall survival than patients with high myostatin levels. Low serum myostatin levels were associated with poor prognosis independent of the Japanese scoring system for ALF ≥3, King's College criteria, or model for end-stage liver disease score >30.5. The combination of serum myostatin levels and prognostic models for ALF significantly stratified patients according to 1-year prognosis. Low serum myostatin levels were associated with a low psoas muscle index, complication rate, and poor prognosis in patients with ALF and LOHF. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with ALF and LOHF.

Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE): Protocol for a Translational Study.

Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers. This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS. The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease. Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted. This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS. ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146. DERR1-10.2196/55723.

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Prognostic and clinicopathological value of systemic inflammation response index (SIRI) in patients with breast cancer: a meta-analysis

Background Many studies have explored the value of the systemic inflammation response index (SIRI) in predicting the prognosis of patients with breast cancer (BC); however, their findings remain controversial. Consequently, we performed the present meta-analysis to accurately identify the role of SIRI in predicting BC prognosis. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were comprehensively searched between their inception and February 10, 2024. The significance of SIRI in predicting overall survival (OS) and disease-free survival (DFS) in BC patients was analyzed by calculating pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results Eight articles involving 2,997 patients with BC were enrolled in the present study. According to our combined analysis, a higher SIRI was markedly associated with dismal OS (HR = 2.43, 95%CI = 1.42–4.15, p < 0.001) but not poor DFS (HR = 2.59, 95%CI = 0.81–8.24, p = 0.107) in patients with BC. Moreover, based on the pooled results, a high SIRI was significantly related to T3–T4 stage (OR = 1.73, 95%CI = 1.40–2.14, p < 0.001), N1–N3 stage (OR = 1.61, 95%CI = 1.37–1.91, p < 0.001), TNM stage III (OR = 1.63, 95%CI = 1.34–1.98, p < 0.001), and poor differentiation (OR = 1.25, 95%CI = 1.02–1.52, p = 0.028). Conclusion According to our results, a high SIRI significantly predicted poor OS in patients with BC. Furthermore, elevated SIRI was also remarkably related to increased tumor size and later BC tumor stage. The SIRI can serve as a novel prognostic biomarker for patients with BC.

Pan-cancer analysis of polo-like kinase family genes reveals polo-like kinase 1 as a novel oncogene in kidney renal papillary cell carcinoma

BackgroundPolo-like kinases (PLKs) are a kinase class of serine/threonine with five members that play crucial roles in cell cycle regulation. However, their biological functions, regulation, and expression remain unclear. This study revealed the molecular properties, oncogenic role, and clinical significance of PLK genes in pan-cancers, particularly in kidney renal papillary cell carcinoma (KIRP). MethodsWe evaluated the mutation landscape, expression level, and prognostic values of PLK genes using bioinformatics analyses and explored the association between the expression level of PLK genes and tumor microenvironment (TME), immune subtype, cancer immunotherapy, tumor stemness, and drug sensitivity. Finally, we verified the prognostic value in patients with KIRP through univariate and multivariate analyses and nomogram construction. ResultsPLK genes are extensively altered in pan-cancer, which may contribute to tumorigenesis. These genes are aberrantly expressed in some types of cancer, with PLK1 being overexpressed in 31 cancers. PLK expression is closely associated with the prognosis of various cancers. The expression level of PLK genes is related with sensitivity to diverse drugs and cancer immunity as well as cancer immunotherapy. Importantly, we verified that PLK1 was overexpressed in KIRP tissues and could be an unfavorable prognostic biomarker in patients with KIRP. Hence, PLK1 may serve as an oncogenic gene in KIRP and should be explored in future studies. ConclusionsOur study comprehensively reports the molecular characteristics and biological functions of PLK family gens across human cancers and recommends further investigation of these genes as potential biomarkers and therapeutic targets, especially in KIRP.

Correlation between Red Cell Distribution Width (RDW) and Mean Corpuscular Volume (MCV) as a Prognostic Biomarker for Diabetic Nephropathy Patients in a South Indian Hospital

Context: Diabetic nephropathy is one of the microvascular complications of diabetes mellitus, capable of leading to end-stage renal disease. Diabetic nephropathy could only be identified through renal biopsy testing, which is expensive and can impose a financial burden on patients. Therefore, there is a necessity to develop a cost-effective method for identifying diabetic nephropathy. Aim: To evaluate the correlation between RBC parameters, such as RDW and MCV values, as prognostic biomarkers for patients with diabetic nephropathy. Methods and Material: Study Design: Prospective comparative study. Study Site: Sudha Institute of Medical Science, Erode. Study Duration: Study was carried out over six-months. Sample Size: 101 diabetic nephropathy patients and 101 type 2 diabetes mellitus patients. Statistical Analysis: Pearson correlation. Results: The majority of diabetic nephropathy patients were 40 years old or older, and most of them were males. Among the study participants, a significant number of male participants had habits of smoking and alcohol consumption. The duration of diabetes and BMI exhibited a strong correlation with the occurrence of diabetic nephropathy. Furthermore, there were notable increases in urea, creatinine, FBS, RBS, PPBS, and HbA1C, alongside a decrease in MCV and eGFR as diabetic nephropathy progressed. Conclusions: Our research indicates a positive correlation between RDW and HbA1c, FBS, RBS, PPBS, urea, and creatinine. In contrast, negative correlation of RDW with MCV and eGFR. MCV is negatively correlated with HbA1c, FBS, RBS, PPBS, urea, creatinine. In contrast, positive correlation between MCV and eGFR.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. To investigate the ability of NLR to predict ESLD. Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Plasma Levels of Pentraxin 3: A Potential Prognostic Biomarker in Urinary Bladder Cancer Patients.

Urinary bladder cancer (BC) represents a major health issue, and identifying novel biomarkers for early disease detection and outcome prediction is paramount. It has already been established that the immune system plays a role in tumour initiation and progression in which the inflammatory marker pentraxin 3 (PTX3) might be involved, presenting a variety of functions in different cancers. The aim of this study was to investigate whether plasma levels of PTX3 could be used as a biomarker for patients with BC. Plasma levels of PTX3 were determined in 118 BC patients and 50 controls by ELISA. Patients with BC had significantly higher PTX3 levels compared to controls. The value as a diagnostic biomarker is probably limited, however, since no significant difference in PTX3 levels was seen between patients with non-muscle-invasive BC and controls; they were seen only between patients with muscle-invasive disease and controls. However, the potential value of PTX3 as a prognostic biomarker was indicated by significantly higher PTX3 levels in patients who developed metastatic disease during follow-up compared to patients who did not develop metastatic disease. The conclusions from this study are that plasma levels of PTX3 have limited value as a diagnostic biomarker, although they have potential as a prognostic biomarker for patients with BC.

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy.

The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin-hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy.

The 6-h lactate clearance rate in predicting 30-day mortality in cardiogenic shock

BackgroundEarly evaluation of prognosis in cardiogenic shock (CS) is crucial for tailored treatment selection. Both lactate clearance and lactate levels are considered useful prognostic biomarkers in patients with CS. However, there is yet no literature comparing the 6-h lactate clearance rate (Δ6Lac) with lactate levels measured at admission (L1) and after 6 h (L2) to predict 30-day mortality in CS. MethodsIn this observational cohort study, 95 patients with CS were treated at Department of Intensive Care Unit, Yiwu Central Hospital between January 2020 and December 2022. Of these, 88 patients met the eligibility criteria for inclusion. The lactate levels were measured after admission (L1) as the baseline lactate value, and were measured after 6 h (L2) following admission. The primary endpoint of the study was survival rate at 30 days. A receiver operating characteristic curve was used for data analysis. Univariate and multivariate Cox regression analyses were performed based on Δ6Lac. Kaplan–Meier (KM) survival curves were generated to compare the 30-day survival rates among L1, L2, and Δ6Lac. ResultsThe Δ6Lac model showed the highest area under the curve value (0.839), followed by the L2 (0.805) and L1 (0.668) models. The Δ6Lac model showed a sensitivity of 84.2% and specificity of 75.4%. The L1 and L2 models had sensitivities of 57.9% each and specificities of 89.9% and 98.6%, respectively. The cut-off values for Δ6Lac, L1, and L2 were 18.2%, 6.7 mmol/L, and 6.1 mmol/L, respectively. Univariate Cox regression analysis revealed a significant association between Δ6Lac and 30-day mortality. After adjusting for five models in multivariate Cox regression, Δ6Lac remained a significant risk factor for 30-day mortality in patients with CS. In our fifth multivariate Cox regression model, Δ6Lac remained a risk factor associated with 30-day mortality (hazard ratio [HR]=5.14, 95% confidence interval [CI]: 1.48 to 17.89, P=0.010) as well as L2 (HR=8.42, 95% CI: 1.26 to 56.22, P=0.028). The KM survival curve analysis revealed that L1 >6.7 mmol/L (HR=8.08, 95% CI: 3.23 to 20.20, P <0.001), L2 >6.1 mmol/L (HR=25.97, 95% CI: 9.76 to 69.15, P <0.001), and Δ6Lac ≤18.2% (HR=8.92, 95% CI: 3.95 to 26.95, P <0.001) were associated with a higher risk of 30-day mortality. ConclusionsΔ6Lac is a better predictor of 30-day mortality in CS than lactate levels at admission. It has a predictive value equivalent to that of lactate level at 6 h after admission, making it an important surrogate indicator for evaluating the suitability as well as poor prognosis after CS treatment. We found that a cut-off value of 18.2% for Δ6Lac provided the most accurate assessment of early prognosis in CS.

High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer.

Leucine-rich α-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival. In this study, we assessed serum levels of LRG-1 in patients with early BC and investigated its correlation with the presence of disseminated tumor cells (DTCs) in the bone marrow and survival outcomes. Serum LRG-1 levels of 509 BC patients were determined using ELISA and DTCs were assessed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. We stratified LRG-1 levels according to selected clinical parameters. Using the log-rank (Mantel-Cox) test and multivariate Cox regression analysis, Kaplan-Meier survival curves and prognostic relevance were assessed. Mean serum levels of LRG-1 were 29.70 ± 8.67µg/ml. Age was positively correlated with LRG-1 expression (r = 0.19; p < 0.0001) and significantly higher LRG-1 levels were found in patients over 60years compared to younger ones (30.49 ± 8.63µg/ml vs. 28.85 ± 8.63µg/ml; p = 0.011) and in postmenopausal patients compared to premenopausal patients (30.15 ± 8.34µg/ml vs. 26.936.94µg/ml; p = 0.002). Patients with no DTCs showed significantly elevated LRG-1 levels compared to the DTC-positive group (30.51 ± 8.69µg/ml vs. 28.51 ± 8.54µg/ml; p = 0.004). Overall and BC-specific survival was significantly lower in patients with high serum LRG-1 levels (above a cut-off of 33.63µg/ml) compared to patients with lower LRG-1 levels during a mean follow-up of 8.5years (24.8% vs. 11.1% BC-specific death; p = 0.0003; odds ratio 2.63, 95%CI: 1.56-4.36). Multivariate analyses revealed that LRG-1 is an independent prognostic marker for BC-specific survival (p = 0.001; hazard ratio 2.61). This study highlights the potential of LRG-1 as an independent prognostic biomarker in patients with early BC.

Bioinformatics analysis for the identification of Sprouty-related EVH1 domain-containing protein 3 expression and its clinical significance in thyroid carcinoma

The poorly differentiated thyroid carcinoma (THCA) subtype is associated with an aggressive disease course, a less favorable overall prognosis, and an increased risk of distant organ metastasis. In this study, our objective was to explore the potential utility of the Sprouty-related EVH1 domain-containing protein 3 (SPRED3) as a biomarker for early diagnosis and prognosis in THCA patients. The differentially expressed prognostic-related genes associated with THCA were identified by querying The Cancer Genome Atlas (TCGA) database. The difference in the expression of the SPRED3 gene between thyroid carcinoma (THCA) tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) and further validated through immunohistochemistry. Univariate and multivariate Cox regression models were used, along with clinical information from THCA patients, to analyze the prognostic value of the SPRED3 gene in THCA patients. Functional enrichment analysis was subsequently performed to elucidate the molecular mechanisms underlying the regulatory effects of the SPRED3 gene on thyroid carcinoma. Additionally, we calculated the percentage of infiltrating immune cells in THCA patients and evaluated their correlation with SPRED3 gene expression. Compared with those in noncancerous thyroid tissue, the gene and protein expression levels of SPRED3 were found to be elevated in thyroid carcinoma tissues. Furthermore, the expression of SPRED3 in thyroid carcinoma exhibited significant correlations with tumor location, histological grade, pathological stage, and tumor node metastasis classification (TNM) stage. Univariate and multivariate Cox proportional hazards (Cox) regression analyses demonstrated that SPRED3 could serve as an independent prognostic factor for predicting the overall survival of THCA patients. The results of functional enrichment analysis suggested the potential involvement of SPRED3 in the regulation of extracellular matrix organization, epidermal development, signaling receptor activator activity, skin development, receptor ligand activity, glycosaminoglycan binding, neuroactive ligand‒receptor interaction, the IL-17 signaling pathway, and the PI3K-Akt signaling pathway. Additionally, there were significant correlations between the expression level of the SPRED3 gene and the infiltration of various immune cells (eosinophils, central memory T cells, neutrophils, macrophages, and NK cells) within the thyroid tumor microenvironment. SPRED3 can be used as a prognostic biomarker in patients with THCA could potentially be therapeutic target for THCA.

Prognostic Value of Apparent Diffusion Coefficient (ADC) in Patients with Diffuse Gliomas.

This study aimed to evaluate potential posttreatment changes in ADC values within the tissue surrounding the enhancing lesion, particularly in areas not exhibiting MRI characteristics of involvement. Additionally, the objective was to investigate the correlations among ADC values, treatment response, and survival outcomes in individuals diagnosed with gliomas. This retrospective study included a total of 49 patients that underwent either stereotactic biopsy or maximal surgical resection. Histologically confirmed as Grade III or IV gliomas, all cases adhered to the 2016 and 2021 WHO classifications, with subsequent radio-chemotherapy administered post-surgery. Patients were divided into two groups: short and long survival groups. Baseline and follow-up MRI scans were obtained on a 1.5 T MRI scanner. Two ROI circles were positioned near the enhancing area, one ROI in the NAWM ipsilateral to the neoplasm and another symmetrically in the contralateral hemisphere on ADC maps. At follow-up there was a significant difference in both ipsilateral and contralateral NAWM between the two groups, -0.0857 (p = 0.004) and -0.0607 (p = 0.037), respectively. There was a weak negative correlation between survival and ADC values in ipsilateral and contralateral NAWM at the baseline with the correlation coefficient -0.328 (p = 0.02) and -0.302 (p = 0.04), respectively. The correlation was stronger at the follow-up. The findings indicate that ADC values in normal-appearing white matter (NAWM) may function as a prognostic biomarker in patients with diffuse gliomas.

Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation.

Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction. According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0-1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation. A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml. Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction.

TCHH as a Novel Prognostic Biomarker for Patients with Gastric Cancer by Bioinformatics Analysis.

This study aims to investigate the clinicopathological significance and prognostic value of Trichohyalin (TCHH) in gastric cancer patients through bioinformatics analysis. Data on TCHH expression and clinicopathological information were sourced from The Cancer Genome Atlas (TCGA). The Wilcoxon signed-rank test was used for evaluating the correlation between TCHH mRNA expression levels and clinicopathological features. The predictive significance of TCHH mRNA expression for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in patients with gastric cancer was assessed using Cox regression models. Furthermore, measures of immune cell infiltration in gastric cancer were made, and studies of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were also carried out to investigate the possible roles of TCHH in patients with gastric cancer. Compared to normal tissues, gastric cancer had a considerably higher expression of TCHH mRNA (P < 0.05). Wilcoxon analysis revealed a significant association between TCHH mRNA expression and the pathologic M stage (P = 0.017). High TPMT mRNA levels were also correlated with worse OS, DFS, and PFI in gastric cancer patients (both P < 0.05). TCHH showed significant negative correlations with the levels of NK CD56dim infiltration (r = -0.157, p = 0.002), Th17 cells infiltration (r = -0.235, P < 0.001), and Th2 infiltration (r = -0.195, P < 0.001). Furthermore, enrichment analysis indicated potential involvement in intermediate filament cytoskeleton organization, DNA methylation in gamete generation, cell-cell recognition, and G protein-coupled peptide receptor (GPCRs) activity. The level of TCHH mRNA may serve as a novel prognostic biomarker for gastric cancer patients.

The Apparent Diffusion Coefficient of the Paraspinal and Psoas Muscles Are of Prognostic Relevance in Patients With Hepatocellular Carcinoma Undergoing Transarterial Radioembolization.

Transarterial radioembolization (TARE) is a treatment option for early or intermediate stage hepatocellular carcinoma (HCC). Sarcopenia is defined as loss of muscle strength and quality which can be estimated by imaging modalities and has been associated with prognosis and treatment response in HCC patients. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) can reflect the tissue composition and might be better to determine muscle changes of sarcopenia than the standard method of computed tomography (CT). The present study sought to elucidate ADC values of the abdominal wall muscles as a prognostic factor in patients undergoing TARE. A retrospective analysis was performed between 2016 and 2020. Overall, 52 patients, 9 women (17.3%) and 43 men (82.7%), with a mean age of 69±8.5 years were included into the analysis. In every case, the first pre-interventional magnetic resonance imaging (MRI) including DWI was used to measure the ADC values of paraspinal and psoas muscle. The 12-month survival after TARE was used as the primary study outcome. Overall, 40 patients (76.9%) of the patient cohort died within the 12-month observation period. Mean overall survival was 10.9 months after TARE for all patients. Mean ADC values for all muscles were 1.31±0.13×10-3mm2/s. The ADC values of the paraspinal muscles were statistically significantly higher compared to the ADC values of the psoas muscles (p=0.0031). A positive correlation was identified between mean ADC and the thrombocyte count (r=0.37, p=0.005) and serum bilirubin (r=-0.30, p=0.03). In the multivariate Cox regression analysis, the mean ADC values of all muscles were associated with the survival after 12 months (HR=0.98, 95% CI=0.97-0.99, p=0.04). ADC values of the abdominal wall muscles could be used as a prognostic biomarker in patients with HCC undergoing TARE. These preliminary results should be confirmed by further studies using external validation cohorts and other treatment modalities.