Prognostic Biomarker Research Articles

Deciphering the oncogenic potential of ADAM9 in hepatocellular carcinoma through bioinformatics and experimental approaches

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes.

Long non-coding RNAs as prognostic biomarkers in non-muscle invasive bladder cancer: A systematic review

Traditional prognostic tools for non-muscle invasive bladder cancer (NMIBC) often overestimate progression and recurrence risks, underscoring the need for more precise biomarkers. While long non-coding ribonucleic acids (lncRNAs) have been reviewed in bladder cancer, no review has focused on NMIBC. The aim of this study was to address this gap by investigating the role of lncRNAs in predicting NMIBC survival and progression. A systematic review was conducted using PubMed, Scopus, and Cochrane databases as of July 31, 2024. Prognostic studies investigating the association between lncRNA expression and survival outcomes, such as cancer-specific survival, disease-free survival, recurrence-free survival, or overall survival, using Kaplan-Meier curves or hazard ratios, were included. A total of three studies were analyzed, involving 279 NMIBC patients and focusing on three lncRNAs: urothelial cancer associated 1 (UCA1), growth arrest-specific 5 (GAS5), and up-regulated in non-muscle invasive bladder cancer (UNMIBC). Increased UCA1 expression was strongly associated with poor disease-free survival (hazard ratio (HR): 1.974; 95%CI: 1.061–3.673; p=0.032) and progression-free survival (HR: 3.476; 95%CI: 1.187–10.18; p=0.023). Reduced GAS5 expression was significantly associated with poor disease-free survival (HR: 2.659; 95%CI: 1.348–5.576; p=0.005) and progression-free survival (HR: 6.628; 95%CI: 1.494–29.40; p=0.013). Higher level of UNMIBC was strongly associated with poor recurrence-free survival (HR: 2.362; 95%CI: 1.504–4.837; p=0.007). In conclusion, lncRNAs have potential as prognostic biomarkers in NMIBC, with UCA1 and UNMIBC overexpression and GAS5 underexpression being significant in predicting disease recurrence and progression, highlighting the clinical relevance of monitoring these lncRNAs to improve prognosis and guide treatment decisions.

Serum endocan (ESM-1) as diagnostic and prognostic biomarker in Multisystem inflammatory syndrome in children (MIS-C)

Endothelial-cell-specific molecule-1 (ESM-1) also called endocan is a well-known biomarker for detecting inflammation, endothelial dysfunction (ED), and cardiovascular (CV) risk in COVID-19 patients. Upon SARS-CoV-2 infection, a small percentage of children develop Multisystem Inflammatory Syndrome in children (MIS-C). Whether endocan can be used as a biomarker of MIS-C is unknown. In this study, we assessed ESM-1 levels in MIS-C (n = 19) and healthy controls (HC; n = 17). We observed a significant increase in serum ESM-1 levels in MIS-C vs HC (p = 0.0074). In addition, ROC curve analysis demonstrated that this factor has a reasonable discriminatory power between MIS-C patients and HC (AUC of 0.7585). Notably, after one week of hospitalization and care, ESM-1 levels decreased, and this reduction was observed also for other inflammatory and pro-thrombotic markers like C-reactive protein, procalcitonin, fibrinogen, D-dimer, and ferritin, suggesting a general recovery trend in MIS-C patients. In fact, we observed that serum ESM-1 levels positively correlated with procalcitonin (PCT) (r = 0.468; p = 0.043). Finally, logistic regression analysis demonstrated an association between endocan levels and cardiac complications like myocarditis. Therefore, this study suggests that ESM-1 is a valuable diagnostic and prognostic biomarker in patients with MIS-C that may help identify those MIS-C patients at higher risk for cardiovascular complications and guide treatment strategies.

Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma.

Glycine N-acyltransferase (GLYAT), known to influence glycine metabolism, has been implicated in the progression of various malignant tumours. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unexplored. Here, GLYAT expression levels in HCC tissues were significantly reduced compared to normal liver tissues. Similarly, GLYAT expression levels in Huh 7, HepG2, PLC and SK-HEP1 were lower than those in LO2. Receiver operating characteristic curve analysis demonstrated that GLYAT exhibited good diagnostic performance for HCC. Kaplan-Meier analyses suggested that decreased GLYAT expression was correlated with poorer progress in HCC. Low GLYAT expression was significantly associated with gender and histologic grade. Multivariate Cox regression analysis identified low GLYAT expression and T stage as independent prognostic factors. Nomograms based on GLYAT mRNA expression and T stage showed good concordance with actual survival rates at 1, 2, 3 and 5 years. Moreover, GLYAT downregulation in the Huh 7 cell line enhanced cell proliferation, invasion and migration abilities, while GLYAT overexpression in the HepG2 cell line inhibited these abilities. HCC patients with low GLYAT expression exhibited a predisposition to immune escape and poor response to immunotherapy. This research revealed that GLYAT holds promise as both a prognostic biomarker and a potential therapeutic target in HCC.

Cancer-associated Macrophage-like Cells as a Prognostic Biomarker in Solid Tumors

Cancer-associated Macrophage-like Cells as a Prognostic Biomarker in Solid Tumors

Contributions of Tissue Inhibitor of Metalloproteinase-1 Genotypes to the Risk of Metastasis in Gastric Cancer.

In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status. TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing. The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis. The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted.

NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma.

Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immunohistochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade (P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma.

WNT7B promotes cancer progression via WNT/β-catenin signaling pathway and predicts a poor prognosis in oral squamous cell carcinoma

BackgroundWNT7B is a glycoprotein that plays a crucial role in tumorigenesis. This study aimed to investigate the role of WNT7B in oral squamous cell carcinoma (OSCC).MethodsBioinformatic databases, immunohistochemistry, a real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to detect WNT7B expression in OSCC. The clinical and prognostic importance of WNT7B expression was evaluated. WNT7B expression was examined in oral leukoplakia and carcinoma induced by 4-nitroquinoline 1-oxide in mice. Loss- and gain-of-function analyses were performed to elucidate the role of WNT7B in OSCC cells. Subcutaneous tumor model was established to observe the effects of WNT7B on tumor growth. Co-Immunoprecipitation was used to explore the Frizzled receptors that WNT7B may bind to.ResultsWNT7B upregulated in OSCC and associated with lymph node metastasis, perineural invasion, and an unfavorable prognosis in patients with OSCC. A gradual increased in WNT7B expression during the malignant progression of OSCC. WNT7B promoted cell proliferation, migration, invasion, while silencing WNT7B abolished these effects. Knocking down the expression of WNT7B inhibits tumor growth in vivo. WNT7B functions by binding to the Frizzled 7 receptor and facilitates the nuclear translocation of β-catenin.ConclusionsWNT7B contributes to the progression of OSCC by modulating the WNT/β-catenin signaling pathway. These findings highlight the potential of WNT7B as a novel prognostic biomarker and promising therapeutic target for OSCC.

HOXA7 Expression Is an Independent Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Background/Objectives: Homeobox (HOX) genes encode conserved transcription factors essential for tissue and organ development and cellular differentiation. In humans, these genes are organized into four clusters: HOXA, HOXB, HOXC, and HOXD. While HOX genes have been extensively studied in cancer biology, their roles in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Given the increasing incidence and high mortality rate of ESCC, exploring the molecular drivers of this tumor is urgent. Methods: Therefore, this study investigated the mutational landscape and expression profiles of HOX genes in ESCC and their differentially expressed targets using ESCC data from The Cancer Genome Atlas (TCGA) and two independent transcriptome datasets. Results: We found that copy number alterations and single nucleotide variations were rare, while seven HOX genes (HOXA2, HOXA7, HOXB13, HOXC9, HOXC10, HOXC13, and HOXD10) were significantly differentially expressed in ESCC compared to paired non-malignant mucosa. Further analysis identified 776 potential HOX target genes differentially expressed in ESCC, many of which are involved in critical cancer pathways such as PI3K-AKT, cell cycle regulation, and epithelial–mesenchymal transition (EMT). The HOXA7 overexpression was associated with poor overall survival rates in ESCC. This finding opens new possibilities for targeted therapies, offering hope for improved patient outcomes. Conclusions: Thus, this study underscored the pivotal role of HOX gene dysregulation in ESCC and classified HOXA7 as a potential prognostic biomarker in this tumor.

Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. This retrospective cohort study included women aged 18years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

PDE1A in epithelial ovarian cancer: Oncogenic role, metastatic association, and potential as a prognostic biomarker and therapeutic target

PDE1A in epithelial ovarian cancer: Oncogenic role, metastatic association, and potential as a prognostic biomarker and therapeutic target

Pan-cancer analysis of IRF1 focusing on prognostic and immunological roles in non-small cell lung cancer

Interferon regulatory factor 1 (IRF1) significantly affects tumour occurrence and development. This study aimed to analyse its function as a pan-cancer prognostic indicator. We compared IRF1 expression and prognostic significance in normal and tumour samples from different databases. Accordingly, we performed in vitro experiments and immunohistochemistry (IHC) to investigate the role of IRF1 in non-small cell lung cancer (NSCLC). Our findings indicate that IRF1 expression is significantly correlated with prognosis, the tumour microenvironment, and immune cell infiltration. Furthermore, receiver operating characteristic (ROC) analysis revealed that IRF1 had high accuracy in distinguishing cancerous tissues from normal ones. Notably, IRF1 expression was linked to immune-related and immune checkpoint genes. Cell proliferation, invasion, and migration were significantly related to IRF1 expression. IHC indicated that IRF1 was downregulated in NSCLC tissues. Our study provides comprehensive bioinformatic analysis and experimental verification of IRF1, suggesting its potential as a prognostic biomarker in cancer.

Recent Approaches on Molecular Markers, Treatment and Novel Drug Delivery System Used for the Management of Colorectal Cancer: A Comprehensive Review.

Colorectal cancer affects 1 in 25 females and 1 in 24 males, making it the third most frequent cancer with over 6,08,030 deaths worldwide, despite advancements in detection and treatments, including surgery, chemotherapeutics, radiotherapy, and immune therapeutics. Novel potential agents have increased survival in acute and chronic disease conditions, with a higher risk of side effects and cost. However, metastatic disease has an insignificant long-term diagnosis, and significant challenges remain due to last-stage diagnosis and treatment failure. Early detection, survival, and treatment efficacy are all improved by biomarkers. The advancement of cancer biomarkers' molecular pathology and genomics during the last three decades has improved therapy. Clinically useful prognostic biomarkers assist clinical judgment, for example, by predicting the success of EGFR-inhibiting antibodies in the presence of KRAS gene mutations. Few biomarkers are currently used in clinical settings, so further research is still needed. Nanocarriers, with materials like Carbon nanotubes and gold nanoparticles, provide targeted CRC drug delivery and diagnostics. Light-responsive drugs with gold and silica nanoparticles effectively target and destroy CRC cells. We evaluate the potential use of the long non-coding RNA (non-coding RNA) oncogene plasmacytoma variant translocation 1 (PVT1) as a diagnostic, prognostic, and therapeutic biomarker, along with the latest nanotech breakthroughs in CRC diagnosis and treatment.

METTL3/YTHDF1 stabilizes CORO6 expression promoting osteosarcoma progression through glycolysis

This study investigates the role of CORO6 (Coronin 6) in the development of osteosarcoma. Osteosarcoma is a common malignant bone tumor in children and adolescents, characterized by rapid and irregular bone growth and a high risk of distant lung metastasis. CORO6 is a member of the Coronin family, known for its conserved WD40 repeat domain. This structure allows CORO6 to inhibit actin dynamics through interactions with F-actin and Arp2/3, thereby affecting the organization of the cytoskeleton. Our research found that in osteosarcoma patients, the levels of CORO6 are significantly elevated. Experimental observations showed that reducing the expression of CORO6 significantly inhibits the growth, migration, and invasion abilities of osteosarcoma cells. Moreover, in vivo experiments demonstrated that the absence of CORO6 effectively inhibits the growth of osteosarcoma in animal models. We also discovered that CORO6 promotes the proliferation, migration and invasion capabilities of osteosarcoma cells by activating the Wnt/β-catenin signaling pathway. Moreover, CORO6 play a critical important role in glycosis of osteosarcoma cells. Mechanically, we found that METTL3/YTHDF1 induced m6A modification of CORO6 mRNA promoted the expression of CORO6 by enhancing its stability. These findings offer new directions for the treatment of osteosarcoma, suggesting that CORO6 could be a novel prognostic biomarker and an effective therapeutic target for patients.In summary, CORO6, as an oncogene, plays a key role in the development of osteosarcoma, providing a crucial theoretical basis for the development of new osteosarcoma treatment strategies.

MicroRNAs in Congenital Diaphragmatic Hernia: Insights into Prenatal and Perinatal Biomarkers and Altered Molecular Pathways: microRNAs in Congenital Diaphragmatic Hernia for Pathway Analysis and Prognostic Biomarkers

Congenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect, leading to herniation of abdominal organs into the chest, lung compression, and impaired lung development, often resulting in pulmonary hypertension and lung hypoplasia. Prenatal imaging techniques like ultrasound and MRI provide anatomical predictors of outcomes, but their limitations necessitate novel biomarkers for better prognostic accuracy. This study aims to identify unique circulating maternal, fetal, and neonatal microRNAs (miRNAs) that can distinguish CDH pregnancies from healthy controls and assess their potential as markers of disease severity. We conducted a prospective study involving third-trimester maternal blood, amniotic fluid, cord blood, and neonatal blood samples from pregnancies complicated by CDH and healthy controls. miRNA expression was analyzed using RNA-sequencing, and random forest analysis identified miRNAs distinguishing CDH survivors from non-survivors. Pathway enrichment analyses were performed to explore the biological relevance of differentially expressed miRNAs. Significant miRNA expression differences were observed between CDH and control samples across all sample types. In infant blood, 148 miRNAs were up-regulated, and 36 were down-regulated in CDH cases. Pathway analysis revealed that dysregulated miRNAs in CDH targeted pathways related to protein binding, transcription regulation, and signaling pathways implicated in pulmonary hypertension and lung hypoplasia. Random forest analysis identified miRNAs in maternal blood (miR-7850-5p_L-1R+2, miR-942-3p, and miR-197-3p) that distinguished CDH survivors from non-survivors, with an ROC area under the curve of 1.0. Circulating miRNAs in maternal blood offer promising biomarkers for predicting CDH outcomes. miRNAs from infant blood provide mechanistic insights and potential targets for therapeutic intervention in critical pathways of pulmonary hypertension and lung hypoplasia. Further studies with larger cohorts are needed to validate these findings and explore the clinical application of miRNA biomarkers in CDH management.

Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma

Background & AimsSurgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma (eCCA), but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Here we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for minimal residual disease (MRD) in patients of the STAMP trial, which compares the efficacy of adjuvant capecitabine (CAP) versus gemcitabine plus cisplatin (GemCis). MethodsBetween July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n=50) or CAP (n=51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n=254) were prospectively collected post-surgery before adjuvant chemotherapy (ACT), and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR-NGS assay and was correlated with clinical outcomes. ResultsIn the extended follow-up analysis, median disease-free survival (DFS) and overall survival (OS) did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA-positivity before ACT (HR, 1.8; p=0.029), on-ACT at 12 weeks from C1D1 (HR, 7.72; p<0.001), on-ACT at 24 weeks from C1D1 (HR, 5.24; p<0.001), and anytime post-surgery (HR, 3.81; p<0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA-positivity (HR, 6.7; p<0.001) or who turned ctDNA-positive (HR, 5.8; p<0.001). ConclusionIn patients with resected eCCA, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making. Impact and implicationsThe findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma (eCCA). By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as CA 19-9 and CEA, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on minimal residual disease (MRD) status. Clinical Trial Registration numberNCT03079427

Combined Bone Mineral Density (BMD) and Monocyte-to-Lymphocyte Ratio (MLR) Predicts Recurrence and Prognosis in Hepatocellular Carcinoma Patients Following Liver Resection.

Bone mineral density (BMD) and monocyte-to-lymphocyte ratio (MLR) were recently identified as novel risk factors for patients with several malignancies. The objective of this study was to validate the role of preoperative BMD/MLR as a potential prognostic biomarker in patients with hepatocellular carcinoma (HCC) undergoing liver resection. This investigation enrolled 442 adult patients diagnosed with HCC who underwent liver resection. The patients were classified into high- and low-BMD/MLR groups based on the median, and forward stepwise logistic regression was employed to identify independent predictors for early HCC recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was conducted between patients in the high- and low-BMD/MLR groups. The Kaplan-Meier method was employed to assess and compare the disease-free survival (DFS) and overall survival (OS) between the two cohorts. The study categorized patients into high-BMD/MLR and low-BMD/MLR groups. Forward stepwise logistic regression analysis revealed that low BMD/MLR (P < 0.001), tumor size > 50 mm (P < 0.001), and AFP > 200 ug/L (P = 0.001) were significantly associated with the early recurrence of HCC. Moreover, the results suggested that DFS and OS were significantly shorter in the low-BMD/MLR group compared to the high-BMD/MLR group, both before and after PSM (P < 0.05). Preoperative BMD/MLR held promise as a prognostic biomarker for early recurrence and prognosis in patients with HCC who underwent liver resection. Furthermore, the integration of tumor size, AFP level, and BMD/MLR demonstrated a robust predictive capacity for early recurrence within this patient population.

Inflammatory and cardiac biomarkers in pulmonary arterial hypertension: The prognostic role of IL-34

BackgroundPulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure with significant morbidity and mortality. Inflammatory processes are crucial in PAH pathogenesis, with inflammatory cells and mediators present early in disease progression. IL-34 involvement in inflammatory pathways suggests that IL-34 could be an important player in the progression of PAH, influencing both pulmonary pressures and vascular changes. ObjectiveThe purpose of this study was to investigate the correlation between IL-34 levels and pulmonary arterial hypertension (PAH), aiming to enhance the understanding of the molecular mechanisms underlying PAH and explore IL-34′s potential as a biomarker. MethodsConsecutive PAH patients diagnosed via right-heart catheterization at Malatya Turgut Ozal Eğitim ve Araştırma Hastanesi (Dec 2022 - Apr 2024) were enrolled. Patients were classified into low-risk and high-risk groups based on comprehensive risk assessments that included clinical parameters, hemodynamic measurements and biomarkers, in-line with ESC/ERS guidelines. Serum IL-34, hs-CRP, and NT-proBNP levels were measured and compared with those of healthy controls. Echocardiographic assessments and statistical analyses, including ROC analysis, were conducted to evaluate biomarker significance and predictive capabilities. ResultsThe mean age of low-risk and high-risk PAH patients was 42 ± 7.2 years and 45 ± 5.5 years, respectively. The mean age of the control group was 40 ± 6.4 years. Males comprised 54.29 % of the low-risk group, 56 % of the high-risk group, and 53.3 % of the control group. IL-34 and hs-CRP levels were significantly elevated in PAH patients compared to controls. IL-34 correlated positively with systolic pulmonary artery pressure, RA area, and NT-proBNP levels. Multivariate analysis revealed that IL-34 and hs-CRP were independent predictors of PAH. IL-34 levels>29.8 pg/mL predicted PAH with 78 % sensitivity and 69 % specificity, while levels >44.4 pg/mL predicted high-risk PAH with 84 % sensitivity and 77 % specificity. ConclusionElevated IL-34 and hs-CRP levels are associated with PAH severity and right ventricular dysfunction, suggesting IL-34′s potential as a diagnostic and prognostic biomarker. Further research is needed to validate these findings and explore IL-34-targeted therapies in pH management.

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma.

Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015). Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

The non-canonical RNA binding protein RAN stabilizes the mRNA of intranuclear stress granule assembly factor G3BP1 in nasopharyngeal carcinoma

RNA binding proteins play critical roles in tumor progression by participating in the post-transcriptional regulation of RNA. However, the levels and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. Here we identified a non-canonical RNA binding protein RAN that has the most significant role in NPC progression by a small siRNA pool screening. Functionally, RAN facilitates NPC proliferation and metastasis in vitro and in vivo. High levels of RAN are associated with poor prognosis of NPC patients and can be performed as a prognostic biomarker. Mechanistically, RAN increases the nucleus import of TDP43 and enhances TDP43 nuclear distribution. On the other hand, RAN is directly bound to the coding sequence of G3BP1 mRNA and serves as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3′ untranslated region. These contribute to increasing G3BP1 mRNA stability in the nucleus and lead to up-regulation of G3BP1, which further enhances AKT and ERK signaling and ultimately promotes NPC proliferation and metastasis. These findings reveal that RAN stabilizes intranuclear G3BP1 mRNA by dual mechanisms: recruiting TDP43 into the nucleus and enhancing its interaction with G3BP1 mRNA, suggesting a critical role of RAN in NPC progression and providing a new regulation framework of RBP-RNA.