Unfavorable Prognosis In Patients Research Articles

IgG-Associated Hypocomplementemia in Neonatal Lupus: A Retrospective Multicenter Study.

Hypocomplementemia, defined as a complement C3 or C4 level below the normal lower limit, is strongly associated with an unfavorable prognosis in patients with autoimmune diseases. This study aimed to explore the clinical features and outcomes of patients with neonatal systemic lupus erythematosus (NLE) with hypocomplementemia. This retrospective clinical study was conducted across four tertiary hospitals in Eastern China on January 1, 2011, and December 31, 2023. This study included 91 patients with NLE. Patients were classified into hypocomplementemic and non-hypocomplementemic groups according to their serum C3 and/or C4 levels. Risk factors for the development of hypocomplementemia were explored using univariate/multifactorial analyses, organ involvement, and follow-up outcomes were compared between groups. The number of NLE patients with hypocomplementemia was 36 (39.56%). Hypocomplementemia group had a significantly lower proportion of fish oil supplementation during pregnancy, a higher proportion of cesarean deliveries, mothers with systemic lupus erythematosus, double antibody positivity for anti-SSA and anti-SSB, and higher serum IgG levels. Multivariate analyses showed that maternal allergic diseases, double antibody positivity, and serum IgG levels were risk factors for hypocomplementemia. Baseline IgG levels negatively correlated with complement C3 and C4 levels. NLE Patients with hypocomplementemia are more likely to have thrombocytopenia, hypoproteinemia, or gastrointestinal involvement than those without hypocomplementemia. Systemic application of glucocorticoids was significantly more prevalent in the hypocomplementemia group. Long-term follow-up revealed that allergy-associated disorders were common in patients with NLE and hypocomplementemia, followed by developmental delay, severe infections, attention- deficit hyperactivity disorder, and anxiety/depression, respectively. Log-rank analysis revealed that these patients had significantly higher frequencies of allergic diseases and developmental delays later in life. Maternal allergic diseases, double antibody positivity, and serum IgG levels were associated with the development of hypocomplementemia in children with NLE. Patients with hypocomplementemia-associated NLE typically exhibit a more severe disease course.

SEPT5 overexpression predicts poor prognosis and promotes progression through feedback regulation of HIF-1α in clear cell renal cell carcinoma.

SEPT5 overexpression predicts poor prognosis and promotes progression through feedback regulation of HIF-1α in clear cell renal cell carcinoma.

Prognostic Significance of Preoperative Perihematomal Edema in Spontaneous Cerebellar Hemorrhage After Minimally Invasive Surgery.

Minimally invasive surgery (MIS), including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, has been widely used in patients with spontaneous cerebellar hemorrhage (SCH). However, the long-term prognosis varies widely. Herein, a case-control study nested within a multicenter cohort was conducted to explore the risk factors for unfavorable prognosis in patients with SCH after MIS. The data on medical history, perioperative computed tomography scans, and 6-month prognosis of the observed patients were collected. A comparison of these variables between patients with favorable outcomes (modified Rankin Scale score ≤ 3) and those with unfavorable outcomes (modified Rankin Scale score ≥ 4) was conducted to investigate prognostic predictors. Eighty patients from four clinical centers were enrolled in the present study. Four factors including advanced age, MIC evacuation, large postoperative perihematomal edema (PHE), and large preoperative PHE were identified as independent risk factors for 6month unfavorable neurological outcome. Subsequent analysis demonstrated that preoperative PHE serves as a reliable predictor of unfavorable neurological outcome at 6months (area under the curve = 0.849). Based on restricted cubic spline analysis, patients were subsequently stratified into a large preoperative PHE (≥ 10ml) subgroup and a small preoperative PHE (< 10ml) subgroup. The incidence of unfavorable outcomes in the large preoperative PHE subgroup (47.4%) was significantly higher than that in the small preoperative PHE subgroup (2.4%). Advanced age, MIC evacuation, large preoperative PHE, and postoperative PHE are independent factors associated with unfavorable outcome in patients with SCH who underwent MIS. Significantly, the large preoperative PHE is an independent predictor for unfavorable long-term neurological outcome, particularly when the preoperative PHE is ≥ 10ml.

Zinc finger protein ZC3H18 is abnormally expressed in esophageal cancer tissues and facilitates the proliferation of esophageal cancer cells.

Esophageal cancer presents significant challenges due to the limited efficacy and severe side effects associated with conventional treatments. The identification of epigenetic regulatory molecules that are aberrantly expressed in tumors is crucial for elucidating the mechanisms underlying the development and progression of esophageal cancer. We performed high-throughput methylation level analysis on cancerous and adjacent tissues from 25 patients, identifying the differentially methylated gene ZC3H18 utilizing Bismark software and data from TCGA. Esophageal cancer cell lines with ZC3H18 knockdown were used to validate the biological role of ZC3H18 in tumorigenesis in vitro and in vivo. Eukaryotic transcriptome sequencing analysis was conducted to investigate the potential mechanisms underlying ZC3H18 function. We identified 30 genes exhibiting significant methylation differences between cancerous and adjacent non-cancerous tissues in 25 patients. Subsequent analysis utilizing the TCGA database revealed that the gene ZC3H18 is aberrantly expressed in tumor tissues and is closely associated with patient prognosis. Examination of esophageal cancer tissue samples demonstrated overexpression of the ZC3H18 protein, which was positively correlated with adverse prognosis indicators, including tumor differentiation, stage, and invasion depth. ZC3H18 knockdown significantly inhibited cellular proliferation, migration, invasion, and damage repair. Additionally, ZC3H18 significantly promoted tumor growth in vivo. The expression of various cytokeratins was significantly reduced following the ZC3H18 gene knockdown. ZC3H18 and multiple keratins were co-localized in esophageal cancer tissue. ZC3H18 gene exhibits differential methylation in esophageal cancer was positively correlated with unfavorable patient prognosis. ZC3H18 plays a critical role in the regulation of biological functions within esophageal tumors.

Enlarged perivascular space in the temporal lobe as a prognostic marker in temporal lobe epilepsy with hippocampal sclerosis.

This study was undertaken to investigate the regional burden of enlarged perivascular spaces (EPVSs) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and explore its prognostic relevance. In this retrospective observational study, EPVSs in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), basal ganglia (BG-EPVS), midbrain, and hippocampus were visually rated in 68 treatment-naïve patients with TLE-HS. Regional EPVS burden was dichotomized into high and low degrees (cutoff: >10 for BG-EPVS/T-EPVS; >20 for CS-EPVS). Cox proportional hazards models were used to determine the potential predictors of seizure freedom (SF; no seizure for >1 year) and delayed SF (SF achieved >6 months after initiating antiseizure medication [ASM]). Multivariate logistic regression using stepwise variable selection based on the Akaike information criterion was performed to investigate whether EPVS burden was associated with medical refractoriness (never achieving SF). Of the 68 patients, 20 were classified into the refractory group (29.4%). The high T-EPVS group had an older epilepsy onset (37.3 ± 12.3 vs. 26.5 ± 13.0 years, p = .005), higher pretreatment seizure density (median = 12.0, interquartile range [IQR] = 5.0-20.0 vs. 4.0, IQR = 2.0-10.5, p = .008), and lower focal to bilateral tonic-clonic seizure prevalence (13.3% vs. 73.6%, p < .001) than the low T-EPVS group. High T-EPVS burden (odds ratio [OR] = 10.908, 95% confidence interval [CI] = 1.895-62.789) was an independent predictor of medial refractoriness, along with female sex (OR = 12.906, 95% CI = 2.214-75.220) and ASM treatment duration (OR = .985, 95% CI = .971-.999). The low T-EPVS group had higher probability of achieving delayed SF than the high T-EPVS group (pLog-rank = .030, pCox regression = .038), whereas the probability of achieving SF was comparable between the two groups (pLog-rank = .053, pCox regression = .146). Increased T-EPVS burden may serve as an imaging marker of unfavorable prognosis in patients with TLE-HS, underscoring the potential role of perivascular dysfunction in diminished ASM response.

AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis.

Rhabdomyosarcoma (RMS) is one of the most common solid tumors in children and adolescents. Patients with relapsed/refractory RMS have limited treatment options, highlighting the urgency for the identification of novel therapeutic targets for RMS. In the present study, aurora kinase B (AURKB) was found to be highly expressed in RMS and associated with unfavorable prognosis of patients. Functional experiments indicated that inhibition of AURKB significantly reduced RMS cell proliferation, induced apoptosis and ferroptosis, and suppressed RMS growth in vivo. The highly expressed AURKB in RMS contributes to the apoptosis and ferroptosis resistance of tumor cells through the nucleophosmin 1 (NPM1)/Sp1 transcription factor (SP1)/acyl-CoA synthetase long-chain family member 5 (ACSL5) axis. Furthermore, inhibition of AURKB exerted an anti-RMS effect together with vincristine both in vitro and in vivo, with tolerable toxicity. The above findings provide insights we believe are new into the tumorigenesis of RMS, especially with regard to apoptosis or ferroptosis resistance, indicating that AURKB may be a potential target for clinical intervention in patients with RMS.

Assessment of prognosis and responsiveness to immunotherapy in colorectal cancer patients based on the level of immune cell infiltration.

To build a new prognostic risk assessment model based on immune cell co-expression networks for predicting overall survival and evaluating the efficacy of immunotherapy for colon cancer patients. The Cancer Genome Atlas (TCGA) database was used to obtain mRNA expression profiling data, clinical information, and somatic mutation data from colorectal cancer patients. The degree of tumor immune cell infiltration of the samples was analyzed using the CIBERSORT algorithm. Co-expression of immune-related genes was analyzed using weighted correlation network analysis (WGCNA) and gene modules were identified. Prognosis-related genes were screened and models were constructed using LASSO-Cox analysis. The models were validated by survival analysis. The prognostic potential of the models was quantitatively assessed using Cox regression analysis and the development of column line plots. Immunotherapy sensitivity analysis was performed using CIBERSORT and TIMER algorithms. Gene biofunction analysis was performed using Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA). And the chemotherapeutic response to different drugs was assessed. We established a novel prognostic model utilizing the WGCNA method, which demonstrated robust predictive accuracy for patient survival. The high-risk subgroup in our model exhibited elevated immune cell infiltration coupled with a higher tumor mutation burden, but the difference in response to immunotherapy was not significant compared to the low-risk group. Furthermore, we identified distinct chemotherapy responses to 39 drugs between these risk subgroups. This study revealed a significant correlation between high levels of immune infiltration and unfavorable prognosis in patients with colon cancer. Furthermore, an accurate prognostic risk prediction model based on the co-expression of relevant genes by immune cells was developed, enabling precise prediction of survival of colon cancer patients. These findings offer valuable insights for accurate prognostication and comprehensive management of individuals diagnosed with colon cancer.

The Overexpression of RTN4 Significantly Associated With an Unfavourable Prognosis in Patients With Lower-Grade Gliomas.

Gliomas, the most prevalent primary malignancy of the central nervous system, is characterised by its high mortality rates and unfavourable prognosis. Despite extensive research, the underlying mechanisms of glioma pathogenesis remain elusive. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases provided the lower-grade gliomas (LGG) transcriptome and related clinical data, which were downloaded separately. It was determined what the clinical data differences were between the two groups based on the median reticulon-4 (RTN4) expression group. The R language's survminer tool was utilised to examine the variations in survival between the RTN4 high and low-expression groups. The GeneMANIA database was searched for genes that might interact with RTN4, and these genes were then used to create extensive coexpression networks. Cox regression analysis, both univariate and multivariate, was used to filter out the independent prognostic factors influencing tumour growth. Based on independent prognostic parameters, a nomogram was created to predict prognosis. The model was assessed both internally and externally using receiver operating characteristic curve (ROC) and correcting curves. The R cibersort package was utilised to assess the level of immune infiltration abundance. We further validated our findings with clinical tissues using immunohistochemistry approaches. Statistical significance was determined using the Wilcoxon signed-rank test, with a p value of < 0.05 considered significant. RTN4 expression in the tumour group was higher than in the normal group (p < 0.001), and a high-expression level was linked to a poor prognosis (p = 0.028). Patients with elevated RTN4 expression exhibited significant differences from normal brain tissue samples when stratified analysis of LGG patients by sex or radiation treatment was performed (p < 0.001). The immune cell infiltration data demonstrated that the two groups' expressions of various immune cells differed, with pDC cells showing the greatest correlation (-0.421). Univariate and multivariate Cox regression study showed that RTN4, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion and nia age could be employed as independent prognostic factors for LGG, and the correction curve of the model fit well. Ultimately, clinical samples' immunohistochemistry revealed that RTN4 was markedly overexpressed in low-grade gliomas. High RTN4 expression was strongly associated with a poor prognosis in LGG patients. RTN4 may serve as a prognostic biomarker for patients with LGG and represents a potential therapeutic target for immunotherapy in this patient population.

GnRHR inhibits the malignant progression of triple-negative breast cancer by upregulating FOS and IFI44L.

GnRHR inhibits the malignant progression of triple-negative breast cancer by upregulating FOS and IFI44L.

Predicting prognosis using stroke-heart indicator: brain natriuretic peptide in patients with aneurysmal subarachnoid hemorrhage.

This study aims to explore the correlation between brain natriuretic peptide (BNP) levels and prognosis in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). This retrospective study included patients diagnosed with aneurysmal subarachnoid hemorrhage (aSAH) at Beijing Tiantan Hospital between January 2015 and September 2021. Plasma BNP levels were measured upon admission and log-transformed to reduce skewness. Elevated BNP was defined as lgBNP ≥1.79 (equivalent to BNP ≥62 pg./mL). The primary outcome was poor prognosis, defined as a modified Rankin Scale (mRS) score ≥ 3 at 90 days. Univariable and multivariable logistic regression analyses were conducted to examine the association between BNP levels and prognosis. Additionally, we assessed the potential impact of incorporating BNP into a predictive model for poor prognosis. The statistical analysis encompassed a total of 932 patients. Among them, 171 individuals experienced unfavorable prognosis (mRS ≥3) during follow-up, and 444 patients had elevated BNP levels, defined as lgBNP ≥1.79. After accounting for confounding factors, elevated BNP levels remained a significant independent risk factor of a poor prognosis (p = 0.047, OR = 1.49, 95%CI = 1.01-2.20). Nevertheless, BNP's predictive value alone might not warrant its inclusion in a prognostic model. Elevated BNP levels independently forecast unfavorable prognosis in patients with aSAH, even though the cutoff value is lower than the cardiology standards. Continuous monitoring and personalized hospitalization plans can be vital for these patients.

Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke.

We aimed to assess whether neuron-specific enolase (NSE) and S100-β levels are associated with early neurological deterioration (END) in patients with acute ischemic stroke (AIS). We conducted a prospective study between March 2022 and October 2023 in 286 patients with AIS. Serum NSE and S100-β levels on admission and at 24 and 48 h after stroke onset were measured using electrochemiluminescence immunoassays. Outcomes included END events within 48 h of admission and unfavorable neurological outcomes at 3 months. Patients with END had higher serum NSE and S100-β levels. Patients with poor prognosis had higher serum NSE and S100-β levels. Serum NSE (on admission) was an independent biomarker for END in AIS patients and for unfavorable recovery at 3 months. In addition, serum S100-β was an independent biomarker of unfavorable recovery after 3 months in patients with AIS. Serum NSE on admission and S100-β at 48 h of stroke onset may serve as biomarkers of short-term clinical outcome in patients with AIS. Elevated serum NSE and S100-β levels may be useful tools to predict prognosis in patients with AIS.

Mutations and their consequences in the development of pancreatic cancer

Pancreatic cancer is a common cancer with a very poor prognosis and aggressive course. The main reason for the highly unfavorable prognosis of patients with pancreatic cancer is its long-term asymptomatic development, which results in the diagnosis being made at a stage when the cancer process is significantly advanced. Despite extensive research in the field of effective diagnosis and treatment of this cancer, patient survival rates are increasing slowly and insignificantly. Pancreatic cancer cells contain many mutations, the most frequently found of which concern the KRAS, TP53, CDKN2A, SMAD4, BRCA1 and BRCA2 genes. Each of these mutations is associated with specific consequences at the molecular level and translates into further cell functioning, including uncontrolled cell division. The occurrence of specific mutations influences the planning of therapeutic procedures and patient prognosis. Many mutations are associated with a hereditary predisposition to cancer, including pancreatic cancer.

BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer.

Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. However, the emergence of resistance to trastuzumab poses significant challenges. To identify the key genes associated with trastuzumab resistance. These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes. High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation. Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance. We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3, followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms. In patients with HER2-positive gastric cancer, there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage, tumor node metastasis stage, as well as poor overall survival and progression-free survival. BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines, where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt (PI3K-AKT) pathway in HER2-positive gastric cancer cells, both in vivo and in vitro. This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer. Thus, the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation, stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis, ultimately leading to trastuzumab resistance.

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.

DLAT promotes triple-negative breast cancer progression via YAP1 activation

ABSTRACT Background Breast cancer (BC) is the most prevalent malignant tumor in women globally. Triple-negative breast cancer (TNBC) represents the most malignant and invasive subtype of BC. New therapeutic targets are urgently needed for TNBC owing to its receptor expression characteristics, which render it insensitive to traditional targeted and endocrine therapies for BC. The role and mechanisms of dihydrolipoamide S-acetyltransferase (DLAT) as a crucial molecule in glycometabolism and cuproptosis-related biological processes in tumors remain to be explored. Methods DLAT expression was investigated using bioinformatics methods and quantitative real-time polymerase chain reaction. Subsequently, the MTT assay, colony formation assay, and migration-invasion assay were performed to validate the effect of DLAT on TNBC cell viability, proliferation, and migration. Cytoplasmic-nuclear separation experiments, western blot analysis, and co-immunoprecipitation assays were performed to elucidate the underlying molecular mechanisms. Results This study revealed a robust correlation between elevated DLAT expression in BC and unfavorable prognosis in patients, with higher expression of DLAT compared to other subtypes in TNBC. Functional cytology experiments indicated that DLAT plays a tumor-promoting role in TNBC. Mechanistic studies showed that DLAT directly interacts with YAP1, leading to the dephosphorylation and activation of YAP1 and its increased nuclear translocation, thereby transcriptionally activating and regulating downstream oncogenes, promoting the malignant phenotype of TNBC. Rescue experiments indicated that DLAT promotes the malignant behavior of TNBC through a YAP1-dependent pathway. Conclusions Our research unveiled the significant involvement of DLAT in TNBC, along with the potential for modulating DLAT/YAP1 activity as a targeted treatment strategy for TNBC.

The up-regulation of PAK2 indicates unfavorable prognosis in patients with serous epithelial ovarian cancer and contributes to paclitaxel resistance in ovarian cancer cells

BackgroundThe main challenge in treating ovarian cancer is chemotherapy resistance. Previous studies have shown that PAK2 is highly expressed in various cancers. This research investigates whether increased PAK2 expression contributes to chemo-resistance and poor prognosis in ovarian cancer.MethodsInitially, bioinformatics analysis was used to assess the importance of PAK2 mRNA up-regulation in ovarian cancer. This was then validated using tissue microarray to confirm PAK2 protein expression and localization in clinical samples. Univariate and multivariate logistic regression analyses were carried out to identify potential risk factors for chemo-resistance in serous epithelial ovarian cancer (EOC), while multivariate Cox regression and Kaplan-Meier analysis were conducted to ascertain prognostic factors for overall survival (OS) and disease-free survival (DFS) in patients with serous EOC. In vitro experiments were conducted to verify if inhibiting PAK2 expression could increase A2780/Taxol cells’ sensitivity to paclitaxel, as shown by evaluating cell proliferation, apoptosis, transwell, and clone formation. Additionally, the interaction between PAK2, lnc-SNHG1, and miR-216b-5p was verified using RIP and luciferase reporter assays. Rescue experiments were undertaken to examine the influence of the lnc-SNHG1/miR-216b-5p/PAK2 axis on the development of paclitaxel resistance in A2780/Taxol cells.ResultsThe bioinformatics analysis indicated a notable increase in PAK2 expression in ovarian malignant tumors compared to adjacent tissues, particularly in patients with stage III-IV disease compared to those with stage I-II disease (P = 0.0056). Elevated levels of PAK2 were linked to reduced OS in ovarian cancer patients, although no significant association was observed with DFS. Immunohistochemistry findings further supported these results, showing positive PAK2 protein expression in chemo-resistant serous EOC tissues, predominantly localized in the cytoplasm, which correlated with poorer OS and DFS outcomes. In vitro experiments demonstrated that the downregulation of PAK2 in A2780/Taxol cells led to a reduction in colony formation, an increase in apoptosis, and a diminished capacity for cell invasion. Subsequent analysis confirmed that lnc-SNHG1 functions as a competitive endogenous RNA (ceRNA) by interacting with miR-216b-5p and regulating PAK2 expression. Rescue experiments demonstrated that lnc-SNHG1 induces resistance to paclitaxel in A2780/Taxol cells by modulating the miR-216b-5p/PAK2 axis.ConclusionsPAK2 shows promise as a predictor of chemotherapy resistance and poor outcomes in ovarian cancer, indicating its potential use as a treatment target to overcome this resistance.

Integrin β1 in breast cancer: mechanisms of progression and therapy.

The therapy for breast cancer (BC), to date, still needs improvement. Apart from traditional therapy methods, biological therapy being explored opens up a novel avenue for BC patients. Integrin β1 (ITGβ1), one of the largest subgroups in integrin family, is a key player in cancer evolution and therapy. Recent researches progress in the relationship of ITGβ1 level and BC, finding that ITGβ1 expression evidently concerns BC progression. In this chapter, we outline diverse ITGβ1-based mechanisms regarding to the promoted effect of ITGβ1 on BC cell structure rearrangement and malignant phenotype behaviors, the unfavorable patient prognosis conferred by ITGβ1, BC therapy tolerance induced by ITGβ1, and lastly novel inhibitors targeting ITGβ1 for BC therapy.As an effective biomarker, ITGβ1 undoubtedly emerges one of targeted-therapy opportunities of BC patients in future. It is a necessity focusing on scientific and large-scale clinical trials on the validation of targeted-ITGβ1 drugs for BC patients.

Postoperative, but Not Preoperative, MELD-3.0 Prognosticates 3-Month Procedural Success in Patients Undergoing Orthotopic Heart Transplantation

Background/Objectives: Multi-organ failure (MOF) often complicates advanced heart failure (HF), contributing to a poor prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale incorporates liver and kidney function parameters. This study aims to evaluate the prognostic significance of the MELD-3.0 score in patients with advanced HF who have undergone heart transplantation (HTx). Methods: The MELD-3.0 score was computed using the average values of the international normalized ratio and bilirubin, creatinine, sodium, and albumin levels during a hospital stay following HTx. The average MELD-3.0 scores from the period of 1 month preceding HTx and 1 week after HTx were analyzed. The primary endpoint of the study was the 6-month total mortality, and the secondary endpoint was ICU hospitalization time after HTx. Results: The analysis included 106 patients undergoing HTx, with a median age of 53 years (44–63), 81% of whom were male. Within 6 months post-HTx, 17 patients (16%) died; those patients had a higher 1-week post-HTx MELD-3.0 score of 18.3 (14.5–22.7) in comparison to survivors, whose average score was 13.9 (9.5–16.4), p &lt; 0.01. There was no difference in MELD 3.0 score in the pre-HTx period: 16.6 (11.4–17.8) vs. 12.3 (8.6–17.1), p = 0.36. The post-HTx MELD-3.0 score independently predicted death: RR 1.17 (95% CI 1.05–1.30), p &lt; 0.01. A Receiver Operating Characteristic (ROC) determined the cut-off value of the MELD-3.0 score as 17.3 (AUC = 0.83; sensitivity—67%; specificity—86%). Survivors with scores above this value had a longer ICU hospitalization time: 7 (5.0–11.0) vs. 12 (8–20) days (p = 0.01). Conclusions: The post-HTx MELD-3.0 score serves as an independent predictor of an unfavorable prognosis in patients with advanced HF undergoing HTx. The evaluation of MELD-3.0 scores provides additional prognostic information in this population.

CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNA) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. In this study, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, whereas elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/β-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC. Significance: CircRREB1 stimulates PGK1 to induce glycolysis and activates the Wnt/β-catenin signaling pathway to maintain stemness in pancreatic cancer, indicating the potential of circRREB1 as a biomarker and therapeutic target.

MCT4 is an independent prognostic factor and affects immune cell infiltration in patients with colorectal liver oligometastases.

Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection. We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling. Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival. MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.