Good Prognostic Value Research Articles

Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling.

We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT<24h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Based on the derivation cohort (n=1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n=556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from-1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.

Systemic inflammation influences the prognosis of patients with radically resected non-small cell lung cancer and correlates with the immunosuppressive microenvironment.

The impact of host condition on prognosis of non-small cell lung cancer (NSCLC) and the interaction between host and NSCLC remain unclear. This study investigated the association between systemic inflammation and prognosis and characteristics of radically resected NSCLC. This study consisted of a cohort study and an exploratory study of institutional prospective databases. All participants underwent video-assisted thoracoscopic lobectomy as the primary treatment. Systemic inflammation was assessed before surgery using the advanced lung cancer inflammation index and the systemic inflammation response index. Next-generation sequencing and multiplex immunofluorescence analysis were conducted to delineate tumor characteristics. In the cohort study including 1507 participants, high inflammation was associated with poor disease-free survival and overall survival before and after propensity score matching and in multivariable analysis. Systemic inflammation showed good prognostic value for stage IA-IB NSCLC, and the prognostic value diminished with upstaging of NSCLC. In the exploratory study including 217 adenocarcinomas, tumor microenvironment of high inflammation group showed a greater abundance of PDL1+ tumor cells and immune cells, which were independent from driver gene mutations and clinicopathological characteristics. Spatial analysis demonstrated a higher frequency of immune-suppressed cellular neighborhood, increased avoidance between immune cells and PDL1- tumor cells and compromised immune killing and presentation in tumor microenvironment of high inflammation group. Systemic inflammation showed limited association with genomic mutations. Systemic inflammation may influence the prognosis of NSCLC at both the systematic level and the local immune response. The correlation between high inflammation and immunosuppressive microenvironment indicates a novel thread for anticancer treatment.

Identification of a novel immune checkpoint molecule V-set immunoglobulin domain-containing 4 that leads to impaired immunity infiltration in pancreatic ductal adenocarcinoma

BackgroundCheckpoint-based immunotherapy has failed to elicit responses in the majority of patients with pancreatic cancer. In our study, we aimed to identify the role of a novel immune checkpoint molecule V-set Ig domain-containing 4 (VSIG4) in pancreatic ductal adenocarcinoma (PDAC).MethodsOnline datasets and tissue microarray (TMA) were utilized to analyze the expression level of VSIG4 and its correlation with clinical parameters in PDAC. CCK8, transwell assay and wound healing assay were applied to explore the function of VSIG4 in vitro. Subcutaneous, orthotopic xenograft and liver metastasis model was established to explore the function of VSIG4 in vivo. TMA analysis and chemotaxis assay were conducted to uncover the effect of VSIG4 on immune infiltration. Histone acetyltransferase (HAT) inhibitors and si-RNA were applied to investigate factors that regulate the expression of VSIG4.ResultsBoth mRNA and protein levels of VSIG4 were higher in PDAC than normal pancreas in TCGA, GEO, HPA datasets and our TMA. VSIG4 showed positive correlations with tumor size, T classification and liver metastasis. Patients with higher VSIG4 expression were related to poorer prognosis. VSIG4 knockdown impaired the proliferation and migration ability of pancreatic cancer cells both in vitro and in vivo. Bioinformatics study showed positive correlation between VSIG4 and infiltration of neutrophil and tumor-associated macrophages (TAMs) in PDAC, and it inhibited the secretion of cytokines. According to our TMA panel, high expression of VSIG4 was correlated with fewer infiltration of CD8+ T cells. Chemotaxis assay also showed knockdown of VSIG4 increased the recruitment of total T cells and CD8+ T cells. HAT inhibitors and knockdown of STAT1 led to decreased expression of VSIG4.ConclusionsOur data indicate that VSIG4 contributes to cell proliferation, migration and resistance to immune attack, thus identified as a promising target for PDAC treatment with good prognostic value.

Association of frailty with clinical outcomes in chronic obstructive pulmonary disease: A retrospective longitudinal cohort study

BackgroundFrailty is a clinical syndrome and common phenomenon in the elderly, particularly when it coexists with chronic obstructive pulmonary disease (COPD). However, the relationship between frailty and its prognosis in COPD patients has not been clearly elucidated. MethodsWe collected electronic data of inpatients who were diagnosed with COPD in the First Affiliated Hospital with Nanjing Medical University (NJMU) from January 2018 to December 2020. In further, we divided them into different groups based on Frailty Index Common Laboratory Tests (FI-LAB). Binary logistic regression was performed to analyze the risk factors associated with COPD. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were applied to validate FI-LAB's value in prognosis. Primary clinical outcomes contained 30-day mortality and readmission. Moreover, we also compared the prognositic value of FI-LAB with Hospital Frailty Risk Score (HRS) by ROC curve, significance was set at P < 0·05. FindingsThe final study included 826 COPD patients, among of them, 30-day mortality and readmission of frailty group was 11·2%, 25·9%, the robust group was 4·3%, 16·0%, and p value was 0·001, 0·004 respectively. Multivariate analysis revealed that smoking, CCI≥3, oral drug≥5, pneumonia, abnormal lymphocyte, abnormal haemoglobin were independent risk factors with frailty. As for the prediction of FI-LAB about frailty in 30-day mortality, the AUC was 0·832, and 30-day readmission was 0·661. As for the prognositic value, FI-LAB and HRS showed no difference in predicting clinical outcomes. InterpretationCOPD individuals have a higher rate of frailty and pre-frailty. There exists a strong correlation between frailty and 30-day mortality in COPD patients, and FI-LAB has good prognostic value in clinical outcomes of patients with COPD.

Renal biopsy - indication and its implications in management of children admitted at a tertiary care hospital, Mangalore

Background: Percutaneous renal biopsy is an established diagnostic tool for identification of renal pathology required for diagnosis, treatment, and prognostication. The present study was conducted to know the common indications and histopathological findings of renal biopsy, impact of biopsy report on treatment, and complications of procedure. Methods: This was a retrospective observational study conducted in the paediatric ward of a tertiary care level hospital. Indications of renal biopsy as suggested by medical records were noted down. Any treatment changes happened after final histopathological report were recorded. Statistical analysis was made using statistical package for the social sciences (SPSS) version 20.0 (IBM, NY). Results: The mean age of patients at which biopsy was done was 9.83±5.31 years. Most common indications of renal biopsy were nephritic onset nephrotic syndrome (34.8%), steroid-resistant nephrotic syndrome (21.7%), steroid-dependent nephrotic syndrome requiring calcineurin inhibitors (CNI) (17.4%), lupus nephritis (8.7%), nephrotic syndrome with later age of onset (8.7%), acute kidney injury (AKI) stage 3 (4.3%) and for evidence of calcineurin inhibitor toxicity (4.3%). Focal segmental glomerulosclerosis (26.1%), minimal change disease (21.7%) and membranoproliferative glomerulonephrosis (17.4%) were the most common histopathological findings. Conclusions: This study reiterates the fact that renal biopsy is one of the decisive and diagnostic procedures and has good prognostic value in further management of medical renal disease.

Plasma mid-regional proadrenomedullin level in children with pulmonary hypertension associated with CHD.

Adrenomedullin has been shown to inhibit proliferation in pulmonary artery smooth muscle cells and to alleviate pulmonary artery collagen accumulation in pulmonary hypertension. We aimed to assess mid-regional proadrenomedullin level in children with pulmonary hypertension due to CHDs. The current study was conducted in the Pediatric Cardiology Unit, Tanta University Hospital, on 50 children with CHDs: twenty-five patients had a complication of pulmonary hypertension and the other 25 patients without pulmonary hypertension. Another 25 children without CHDs were concluded as a control group. We performed complete history taking, full clinical assessment, chest X-ray, electrocardiogram, and echocardiographic assessment. Plasma level of mid-regional proadrenomedullin was assessed using a sandwich enzyme-linked immunosorbent assay test. Our results showed that the mean plasma level of mid-regional proadrenomedullin was significantly increased in patients with pulmonary hypertension. Significant positive correlation was found between mid-regional proadrenomedullin and mean pulmonary artery pressure. The best cut-off point of mid-regional proadrenomedullin as a diagnostic biomarker to discriminate patients with CHDs complicated with pulmonary hypertension was 199.22 nmol/l. Mid-regional proadrenomedullin significantly increased in patients with pulmonary hypertension who died as compared to patients who survived, with the best cut-off point was 428,8 nmol/l. We concluded that plasma levels of mid-regional proadrenomedullin were significantly elevated in children with pulmonary hypertension complicated by the CHDs. It could be used as a cardiac biomarker in these patients, with good diagnostic and prognostic value.

Value of Some Scoring Systems for the Prognosis of Rebleeding and In-Hospital Mortality in Liver Cirrhosis with Acute Variceal Bleeding

Background: Upper gastrointestinal (GI) hemorrhage, caused by acute esophageal variceal bleeding, is a common complication and a leading cause of death in patients with cirrhosis. Therefore, predicting the risk in order to employ an active management to prevent rebleeding and death is crucial. Currently, there are many prognostic scoring systems that have been proposed, but research is needed to find a valid score which can be applied in clinical practice in each country and population. Aims: To compare the value of ALBI (Albumin-Bilirubin), PALBI (Platelet Albumin-Bilirubin), AIMS65, model for end-stage liver disease (MELD), and Child–Pugh scores (CPS) approaches in predicting early rebleeding and in-hospital mortality of acute variceal bleeding in patients with cirrhosis. Subjects and methods: We performed a cross-sectional descriptive study on cirrhotic patients with acute variceal bleeding who were being treated at the Department of Gastroenterology, Intensive care unit—Military Hospital 103 and the Institute for Treatment of Digestive Diseases—108 Military Central Hospital from September 2020 to May 2022. We calculated ALBI, PALBI, AIMS65, MELD, Child–Pugh values and compared them with the rates of early rebleeding and in-hospital mortality. Then, determined and compared the prognostic value through an analysis of the area under the curve (AUC). Results: 222 patients with acute esophageal variceal bleeding were eligible for inclusion in the study. The rates of rebleeding and in-hospital mortality were 9.0% and 6.8%, respectively. Regarding the prognosis of early rebleeding, the ALBI and PALBI scores have good prognostic value (AUROC 0.74; 95% CI: 0.63–0.85 and AUROC 0.7; 95% CI: 0.59–0.81; p = 0.004, respectively), while the Child–Pugh, MELD, AIMS65 scores have little prognostic value, with AUROC &lt; 0.70. Regarding prognosis of in-hospital mortality: the ALBI, PALBI, MELD and AIMS65 all have good value in predicting in-hospital mortality, with AUROC of 0.81 (95% CI: 0.68–0.93, respectively; p &lt; 0.001); 0.8 (95% CI: 0.69–0.91; p &lt;0.001); 0.83 (95% CI: 0.72–0.93; p &lt; 0.001); and 0.82 (95% CI: 0.76–0.87, p &lt; 0.001), respectively. While Child–Pugh score only has medium prognostic value, with AUROC 0.79 (95% CI: 0.66–0.92; p &lt; 0.05). However, there was no significant difference between these prognostic scoring systems. Conclusion: the ALBI, PALBI, MELD and AIMS65 scores all had similar good value in predicting in-hospital mortality, but with early rebleeding prognosis, only ALBI and PALBI had good value. CPS does not show prognostic value like other scores, both in predicting early rebleeding and in-hospital mortality.

Rheumatoid factor is associated with severe COVID-19.

Coronavirus disease 2019 (COVID-19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID-19. We retrospectively collected data from 245 patients who were hospitalized for COVID-19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), and anti-cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID-19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF-positive patients had higher rates of invasive mechanical ventilation and death than RF-negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in-hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50-21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19-1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002-1.005, P < 0.001) were associated with critical COVID-19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve=0.903, P < 0.001) for critical COVID-19. ANA and RF were frequently detected in COVID-19 patients. RF could be a risk factor for critical COVID-19. The results of this study suggest immune dysfunction contributes to the complications of COVID-19.

Assessment of prognostic value of preoperative neutrophil-to-lymphocyte ratio for postoperative mortality and morbidity.

The preoperative elevated neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with poorer outcomes after cancer and cardiovascular surgeries. It is unclear, however, if the predictive value is particular or if it may be applied to other types of surgery. We aimed to assess the prognostic value of preoperative NLR levels for morbidity and mortality after various surgery and determine an optimal threshold for NLR. We conducted a cohort analysis on patients receiving surgery at Sichuan University West China Hospital between 2018 and 2020. Multivariable piecewise regression analysis were used to determine the optimal cutoff value of NLR. Subgroup analysis were performed to verify the correlation. Sensitivity analysis was used to explore the effect of different thresholds. We obtained data from 136,347 patients. The optimal cutoff of NLR was determined as 3.6 [95% CI (3.0, 4.1)] by piecewise regression method. After multivariable adjustment, preoperative high NLR remained significantly associated with increased in-hospital mortality (aOR, 2.19; 95% CI, 1.90-2.52; p < 0.001) and ICU admission after surgery (aOR, 1.69; 95% CI, 1.59-1.79; p < 0.001). Subgroup analyses confirmed the predictive value of high NLR in multiple surgical subgroups, including general, orthopedic, neurosurgical, and thoracic surgery subgroups, otorhinolaryngology, head and neck surgery, and burn plastic surgery. A NLR threshold of 3.6 gave excellent predictive value, whether employed alone or added in an extended model. In conclusion, the association of elevated NLR with higher mortality and ICU admission can be extended to a wider range of procedures. NLR threshold of 3.6 could provide good prognostic value for the prognostic model.

Microdissecting the Hypoxia Landscape in Colon Cancer Reveals Three Distinct Subtypes and Their Potential Mechanism to Facilitate the Development of Cancer.

Hypoxia contributes to tumor progression and confers drug resistance. We attempted to microdissect the hypoxia landscape in colon cancer (CC) and explore its correlation with immunotherapy response. The hypoxia landscape in CC patients was microdissected through unsupervised clustering. The "xCell" algorithms were applied to decipher the tumor immune infiltration characteristics. A hypoxia-related index signature was developed via the LASSO (least absolute shrinkage and selection operator) Cox regression in The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) cohort and validated in an independent dataset from the Gene Expression Omnibus (GEO) database. The tumor immune dysfunction and exclusion (TIDE) algorithm was utilized to evaluate the correlation between the hypoxia-related index (HRI) signature and immunotherapy response. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were performed to verify the mRNA expression levels of five key genes. The Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to examine the cell viability and cell apoptosis. Patients were classified into hypoxia-high, hypoxia-median, and hypoxia-low clusters in TCGA-COAD and verified in the GSE 17538 dataset. Compared with the hypoxia-low cluster, the hypoxia-high cluster consistently presented an unfavorable prognosis, higher immune scores, and stromal scores and elevated infiltration levels of several critical immune and stromal cells. Otherwise, we also found 600 hypoxia-related differentially expressed genes (HRDEGs) between the hypoxia-high cluster and the hypoxia-low cluster. Based on the 600 HRDEGs, we constructed the HRI signature which consists of 11 genes and shows a good prognostic value in both TCGA-COAD and GSE 17538 (AUC of 6-year survival prediction >0.75). Patients with low HRI scores were consistently predicted to be more responsive to immunotherapy. Of the 11 HRI signature genes, RGS16, SNAI1, CDR2L, FRMD5, and FSTL3 were differently expressed between tumors and adjacent tissues. Low expression of SNAI1, CDR2L, FRMD5, and FSTL3 could induce cell viability and promote tumor cell apoptosis. In our study, we discovered three hypoxia clusters which correlate with the clinical outcome and the tumor immune microenvironment in CC. Based on the hypoxia cluster and HRDEGs, we constructed a reliable HRI signature that could accurately predict the prognosis and immunotherapeutic responsiveness in CC patients and discovered four key genes that could affect tumor cell viability and apoptosis.

Identification of prognosis-related cyclin-dependent kinases and potential response drugs in hepatocellular carcinoma

Which cyclin-dependent kinases (CDKs) involved in the progress of hepatocellular carcinoma (HCC) need to be further clarified. To identify prognostic-relevant biomarkers in HCC through a systematic investigation of the prognostic value of CDKs. We explored the relationship between CDKs expression and the prognosis of patients with HCC using multiple online databases. In addition, their biological functions and correlation with the immune system and drug response were investigated. Among the 20 CDKs (CDK1 ~20) altered in HCC, the significantly high expression of CDK1 and CDK4 in patients with HCC was significantly associated with worse prognosis. Interestingly, CDK1 had significant co-occurrence with CDK4 and CDK1-related and CDK4-related signaling pathways are closely related to hepatitis virus-related HCC. We identified multiple transcription factors of CDK1 and CDK4; of those, only four (E2F1, PTTG1, RELA, and SP1) were significantly associated with the prognosis of HCC patients. Genetic alterations in CDKs were significantly correlated with disease-free and progression-free survival, which may be associated with aberrant expression of progesterone receptor. Moreover, we found a significantly positive correlation between CDK1 and CDK4 expression and tumor-infiltrating activated CD4+ T cell and exhausted T cell-related signature. Finally, we identified drugs with good potential prognostic value predicted by CDK1 and CDK4 levels. CDK1 and CDK4 may be potential prognostic biomarkers for HCC. Moreover, targeting four transcription factors (E2F1, PTTG1, RELA, and SP1) combined with immunotherapy may be a new therapeutic strategy for treating HCC patients with high CDK1 and CDK4 expression, especially hepatitis-related HCC.

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC

For hepatocellular carcinoma (HCC) patients, we attempted to establish a new oxidative stress (OS)-related prognostic model for predicting prognosis, exploring immune microenvironment, and predicting the immunotherapy response. Significantly differently expressed oxidative stress-related genes (DEOSGs) between normal and HCC samples from the Cancer Genome Atlas (TCGA) were screened, and then based on weighted gene coexpression network analysis (WGCNA), HCC-related hub genes were discovered. Based on the least absolute shrinkage and selection operator (LASSO) and cox regression analysis, a prognostic model was developed. We validated the prognostic model's predictive power using an external validation cohort: the International Cancer Genome Consortium (ICGC).Then a nomogram was determined. Furthermore, we also examined the relationship of the risk model and clinical characteristics as well as immune microenvironment. 434 DEOSGs, comprising 62 downregulated and 372 upregulated genes (p < 0.05 and |log2FC| ≥ 1), and 257 HCC-related hub genes were recognized in HCC. Afterward, we built a five-DEOSG (LOX, CYP2C9, EIF2B4, EZH2, and SRXN1) prognostic risk model. Using the nomogram, the risk model was shown to have good prognostic value. Compared to the low risk group, HCC patients with high risk had poorer outcomes, worse pathological grades, and advanced tumor stages (p < 0.05). There were significant increases in LOX, EIF2B4, EZH2, and SRXN1 expression in HCC samples, while CYP2C9 expression was decreased. Finally, Real-time PCR (RT-qPCR) confirmed the mRNA expressions of five genes (CYP2C9, EIF2B4, EZH2, SRXN1, LOX) in HCC cell lines. Our study constructed a prognostic OS-related model with strong predictive power and potential as an immunosuppressive biomarker for HCC leading to improving prediction and providing new insights for HCC immunotherapy.

Expression of AKRs superfamily and prognostic in human gastric cancer.

The human aldo-keto reductase (AKRs) superfamily is involved in the development of various tumors. However, the different expression patterns of AKRs and their prognostic value in gastric cancer (GC) have not been clarified. In this study, we analyzed the gene expression and gene methylation level of AKRs in GC patients and the survival data and immune infiltration based on AKRs expression, using data from different databases. We found that the expression levels of AKR1B10, AKR1C1, AKR1C2, and AKR7A3 in GC tissues were lower and the expression level of AKR6A5 was higher in GC tissues than in normal tissue. These differentially expressed genes (AKR1B10, AKR1C1, AKR1C2, AKR7A3, and AKR6A5) were significantly correlated with the infiltration level. The expression of SPI1 and AKR6A5 in GC was positively correlated. Survival analysis showed that GC levels of AKR6A5 reduced or increased mRNA levels of AKR7A3, and AKR1B10 was expected to have higher overall survival (OS), first progression (FP) survival, and postprogression survival (PPS) rates and a better prognosis. Moreover, the expression of AKR1B1 was found to be correlated with the staging of GC. The methylation of AKR6A5 (KCNAB2) at cg05307871 and cg01907457 was significantly associated with the classification of GC. Meta-analysis and ROC curve analysis show that the expression level of AKR1B1 and the methylation of cg16156182 (KCNAB1), cg11194299 (KCNAB2), cg16132520 (AKR1B1), and cg13801416 (AKR1B1) had a high hazard ratio and a good prognostic value. These data suggest that the expression and methylation of AKR1B1 and AKR6A5 are significantly related to the prognosis.

Oncometabolic role of mitochondrial sirtuins in glioma patients.

Mitochondrial sirtuins have diverse role specifically in aging, metabolism and cancer. In cancer, these sirtuins play dichotomous role as tumor suppressor and promoter. Previous studies have reported the involvement of sirtuins in different cancers. However, till now no study has been published with respect to mitochondrial sirtuins and glioma risks. Present study was purposed to figure out the expression level of mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) and related genes (GDH, OGG1-2α, SOD1, SOD2, HIF1α and PARP1) in 153 glioma tissue samples and 200 brain tissue samples from epilepsy patients (taken as controls). To understand the role of selected situins in gliomagenesis, DNA damage was measured using the comet assay and oncometabolic role (oxidative stress level, ATP level and NAD level) was measured using the ELISA and quantitative PCR. Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2α (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls. In case of SIRT3 (p = 0.0322), HIF1α (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed. ROC curve analysis and cox regression analysis showed the good diagnostic and prognostic value of mitochondrial sirtuins in glioma patients. Oncometabolic rate assessment analysis showed significant increased ATP level (p<0.0001), NAD+ level [(NMNAT1 (p<0.0001), NMNAT3 (p<0.0001) and NAMPT (p<0.04)] and glutathione level (p<0.0001) in glioma patients compared to controls. Significant increased level of damage ((p<0.04) and decrease level of antioxidant enzymes include superoxide dismutase (SOD, p<0.0001), catalase (CAT, p<0.0001) and glutathione peroxidase (GPx, p<0.0001) was observed in patients compared to controls. Present study data suggest that variation in expression pattern of mitochondrial sirtuins and increased metabolic rate may have diagnostic and prognostic significance in glioma patients.

The prognostic role of HIF-1α and NF-κB expression in RAS wild-type metastatic colorectal cancer: A Turkish Oncology Group (TOG) study.

Not all RAS wild-type metastatic colorectal cancer (mCRC) patients experience the same benefit from anti-epidermal growth factor receptor (EGFR) treatments. Studies have shown that nuclear factor-κB (NF-κB), hypoxia-inducible factor-1α (HIF-1α), interleukin 8 (IL-8) and transforming growth factor β (TGF-β) may be therapeutic targets for mCRC. The aim of this study was to clarify the prognostic value of NF-κB, HIF-1α, IL-8, and TGF-β expression in patients with left-sided mCRC receiving EGFR inhibitors. Patients with RAS wild-type, left-sided mCRC treated with anti-EGFR on the first line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-κB, HIF-1α, IL-8 and TGF-β was performed from tumor tissues of 88 patients. Patients were divided into NF-κB, HIF-1α, IL-8 and TGF-β expression positive and negative group, moreover, expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2months. Median progression-free survival (PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p = 0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26.9 (15.9-31.9) months in the panitumumab group (p = 0.8). Cytoplasmic NF-κB expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-κB expression intensity low group and 36.5 (20.1-52.8) months in high group (p = 0.03). The mOS of the HIF-1α expression negative group was significantly longer compared with expression positive group (p = 0.014). There was no significant difference in IL-8 and TGF-β expression status on mOS and mPFS (for all, p > 0.05). Positive expression of HIF-1α was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI 1.18-6.52, p = 0.02) and in multivariate analysis (HR 3.69, 95% CI 1.41-9.6, p = 0.008). High cytoplasmic expression intensity of NF-κB was found to have a good prognostic value for mOS (HR 0.47, 95% CI 0.26-0.85, p = 0.01). High cytoplasmic expression intensity of NF-κB and negative expression of HIF-1α could be a good prognostic marker for mOS in RAS wild-type left-sided mCRC.

Evaluation of nestin expression in melanoma, basal cell carcinoma and basosquamous carcinoma

Introduction: Nestin plays a significant role in diagnosis, prognosis, clinical course and/or response to the treatment. Previous studies have investigated the nestin expression in melanoma, however a limited number have focused on basal cell carcinoma (BCC) and basosquamous carcinoma (BSC). Objectives: The current study aimed to investigate nestin expression in melanoma, BCC, and BSC. Materials and Methods: This cross-sectional study was conducted on 40 melanomas, 40 BCC and 40 BSC specimens. Tumor size, lesion location and stage of disease were recorded. Then, nestin staining was conducted in all the present samples, then the amount of nestin expression was assessed. Results: According to the results of this study, nestin was expressed in all melanoma specimens; while it was expressed in 15% of BSC and 25% of BCC specimens. The mean score of nestin expression in melanoma specimens (0.85 ± 2.50) was significantly higher than the BSC and BCC specimens with the means of 0.36±0.15 and 0.44±0.25 respectively (P value &lt;0.001). However, there was no significant difference between BSC and BCC specimens in nestin expression. Additionally, in the melanoma specimens, a significant and direct relationship between nestin expression and the various stages of melanoma with the coefficient of 0.345 (P value = 0.025). Conclusion: The results of the current study showed that expression of nestin could have a good prognostic value in skin melanoma while, there is a significant relationship with its progression. However, in non-melanoma specimens, no distinction can be detected regarding the nestin expression.

A survival nomogram model constructed with common clinical characteristics to assist clinical decisions for diffuse low-grade gliomas: A population analysis based on SEER database.

The prognosis of diffuse low-grade gliomas (DLGGs, WHO grade 2) is highly variable, making it difficult to evaluate individual patient outcomes. In this study, we used common clinical characteristics to construct a predictive model with multiple indicators. We identified 2459 patients diagnosed with astrocytoma and oligodendroglioma from 2000 to 2018 in the SEER database. After removing invalid information, we randomly divided the cleaned patient data into training and validation groups. We performed univariate and multivariate Cox regression analyses and constructed a nomogram. Receiver operating characteristic (ROC) curve, c-index, calibration curve, and subgroup analyses were used to assess the accuracy of the nomogram by internal and external validation. After univariate and multivariate Cox regression analyses, we identified seven independent prognostic factors, namely, age (P<0.001), sex (P<0.05), histological type (P<0.001), surgery (P<0.01), radiotherapy (P<0.001), chemotherapy (P<0.05) and tumor size (P<0.001). The ROC curve, c-index, calibration curve, and subgroup analyses of the training group and the validation group showed that the model had good predictive value. The nomogram for DLGGs predicted patients' 3-, 5- and 10-year survival rates based on these seven variables. The nomogram constructed with common clinical characteristics has good prognostic value for patients with DLGGs and can help physicians make clinical decisions.

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma.

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated. Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed. Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established. Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

New Classification Based on CT and Its Value Evaluation for Fractures of the Lateral Process of the Talus

This study aimed to develop a comprehensive classification system for fractures of the lateral process of the talus (LPTF) based on CT, and to evaluate its prognostic value, reliability and reproducibility. We retrospectively reviewed 42 patients involving LPTF with an average follow-up of 35.9 months for clinical and radiographic evaluations. In order to develop a comprehensive classification, a panel of experienced orthopedic surgeons discussed the cases. All fractures were classified according to Hawkins, McCrory-Bladin and new proposed classifications by 6 observers. The analysis of interobserver and intraobserver agreements was measured using kappa statistics. The new classification included 2 types based on presence of concomitant injuries or not, with type I consisting of 3 subtypes and type II of 5 subtypes. Average AOFAS score was 91.5 in the type Ia of new classification, 86 in type Ib, 90.5 in type Ic, 89 in type IIa, 76.7 in type IIb, 76.6 in type IIc, 91.3 in type IId, and 83.5 in type IIe. Interobserver and intraobserver reliability of the new classification system were almost perfect (κ=0.776 and 0.837, respectively), showing a higher interobserver and intraobserver reliability compared to the Hawkins classification (κ 0.572 and 0.649, respectively) as well as McCrory-Bladin classification (κ=0.582 and 0.685, respectively). The new classification system is a comprehensive one that takes into account concomitant injuries and shows good prognostic value with clinical outcomes. It is more reliable and reproducible and could be a useful tool for decision-making on treatment options for LPTF.

Nucleotide-Binding Oligomerization Domain (NOD)-Like Receptor Subfamily C (NLRC) as a Prognostic Biomarker for Glioblastoma Multiforme Linked to Tumor Microenvironment: A Bioinformatics, Immunohistochemistry, and Machine Learning-Based Study.

Glioblastoma multiforme (GBM) remains the deadliest primary brain tumor. We aimed to illuminate the role of nucleotide-binding oligomerization domain (NOD)-like receptor subfamily C (NLRC) in GBM. Based on public database data (mainly The Cancer Genome Atlas [TCGA]), we performed bioinformatics analysis to visually evaluate the role and mechanism of NLRCs in GBM. Then, we validated our findings in a glioma tissue microarray (TMA) by immunohistochemistry (IHC), and the prognostic value of NOD1 was assessed via random forest (RF) models. In GBM tissues, the expression of NLRC members was significantly increased, which was related to the low survival rate of GBM. Additionally, Cox regression analysis revealed that the expression of NOD1 (among NLRCs) served as an independent prognostic marker. A nomogram based on multivariate analysis proved the effective predictive performance of NOD1 in GBM. Enrichment analysis showed that high expression of NOD1 could regulate extracellular structure, cell adhesion, and immune response to promote tumor progression. Then, immune infiltration analysis showed that NOD1 overexpression correlated with an enhanced immune response. Then, in a glioma TMA, the results of IHC revealed that the increase in NOD1 expression indicated high recurrence and poor prognosis of human glioma. Furthermore, the expression level of NOD1 showed good prognostic value in the TMA cohort via RF. The value of NOD1 as a biomarker for GBM was demonstrated. The possible mechanisms may lie in the regulatory role of NLRC-related pathways in the tumor microenvironment.