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Introduction: To analyze the risk factors affecting recurrence in early-stage hepatocellular carcinoma (HCC) patients treated with ablation and then establish a nomogram to provide a clear and accessible representation of the patients' recurrence risk. Methods: Collect demographic and clinical data of 898 early-stage HCC patients who underwent ablation treatment at Beijing You'an Hospital, affiliated with Capital Medical University from January 2014 to December 2022. Patients admitted from 2014 to 2018 were included in the training cohort, while 2019 to 2022 were in the validation cohort. Lasso and Cox regression was used to screen independent risk factors for HCC patients recurrence, and a nomogram was then constructed based on the screened factors. Results: Age, gender, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, globulin (Glob) and g-glutamyl transpeptidase (g-GT) were finally incorporated in the nomogram for predicting the recurrence-free survival (RFS) of patients. We further confirmed that the nomogram has optimal discrimination, consistency and clinical utility by the C-index, Receiver Operating Characteristic Curve (ROC), calibration curve and Decision Curve Analysis (DCA). Moreover, we divided the patients into different risk groups and found that the nomogram can effectively identify the high recurrence risk patients by the Kaplan-Meier curves. Conclusion: This study developed a nomogram using Lasso-Cox regression to predict RFS in early-stage HCC patients following ablation, aiding clinicians in identifying high-risk groups for personalized follow-up treatments. [ABSTRACT FROM AUTHOR]

BackgroundDisseminated intravascular coagulation (DIC) is a devastating condition, which always cause poor outcome of critically ill patients in intensive care unit. Studies concerning short-term mortality prediction in DIC patients is scarce. This study aimed to identify risk factors contributing to DIC mortality and construct a predictive nomogram.MethodsA total of 676 overt DIC patients were included. A Cox proportional hazards regression model was developed based on covariates identified using least absolute shrinkage and selection operator (LASSO) regression. The prediction performance was independently evaluated in the MIMIC-III and MIMIC-IV Clinical Database, as well as the 908th Hospital Database (908thH). Model performance was independently assessed using MIMIC-III, MIMIC-IV, and the 908th Hospital Clinical Database.ResultsThe Cox model incorporated variables identified by Lasso regression including heart failure, sepsis, height, SBP, lactate levels, HCT, PLT, INR, AST, and norepinephrine use. The model effectively stratified patients into different mortality risk groups, with a C-index of >0.65 across the MIMIC-III, MIMIC-IV, and 908th Hospital databases. The calibration curves of the model at 7 and 28 days demonstrated that the prediction performance was good. And then, a nomogram was developed to facilitate result visualization. Decision curve analysis indicated superior net benefits of the nomogram.ConclusionThis study provides a predictive nomogram for short-term overt DIC mortality risk based on a Lasso-Cox regression model, offering individualized and reliable mortality risk predictions.

Abstract Objective To screen the risk factors affecting the recurrence risk of patients with ampullary carcinoma (AC)after radical resection, and then to construct a model for risk prediction based on Lasso-Cox regression and visualize it. Methods Clinical data were collected from 162 patients that received pancreaticoduodenectomy treatment in Hebei Provincial Cancer Hospital from January 2011 to January 2022. Lasso regression was used in the training group to screen the risk factors for recurrence. The Lasso-Cox regression and Random Survival Forest (RSF) models were compared using Delong test to determine the optimum model based on the risk factors. Finally, the selected model was validated using clinical data from the validation group. Results The patients were split into two groups, with a 7:3 ratio for training and validation. The variables screened by Lasso regression, such as CA19-9/GGT, AJCC 8th edition TNM staging, Lymph node invasion, Differentiation, Tumor size, CA19-9, Gender, GPR, PLR, Drinking history, and Complications, were used in modeling with the Lasso-Cox regression model (C-index = 0.845) and RSF model (C-index = 0.719) in the training group. According to the Delong test we chose the Lasso-Cox regression model (P = 0.019) and validated its performance with time-dependent receiver operating characteristics curves(tdROC), calibration curves, and decision curve analysis (DCA). The areas under the tdROC curves for 1, 3, and 5 years were 0.855, 0.888, and 0.924 in the training group and 0.841, 0.871, and 0.901 in the validation group, respectively. The calibration curves performed well, as well as the DCA showed higher net returns and a broader range of threshold probabilities using the predictive model. A nomogram visualization is used to display the results of the selected model. Conclusion The study established a nomogram based on the Lasso-Cox regression model for predicting recurrence in AC patients. Compared to a nomogram built via other methods, this one is more robust and accurate.

Objective: To screen the risk factors affecting the recurrence risk of patients with ampullary carcinoma (AC)after radical resection, and then to construct a model for risk prediction based on Lasso-Cox regression and visualize it. Methods: Clinical data were collected from 162 patients that received pancreaticoduodenectomy treatment in Hebei Provincial Cancer Hospital from January 2011 to January 2022. Lasso regression was used in the training group to screen the risk factors for recurrence. The Lasso-Cox regression and Random Survival Forest (RSF) models were compared using Delong test to determine the optimum model based on the risk factors. Finally, the selected model was validated using clinical data from the validation group. Results: The patients were split into two groups, with a 7:3 ratio for training and validation. The variables screened by Lasso regression, such as CA19-9/GGT, AJCC 8th edition TNM staging, Lymph node invasion, Differentiation, Tumor size, CA19-9, Gender, GPR, PLR, Drinking history, and Complications, were used in modeling with the Lasso-Cox regression model (C-index = 0.845) and RSF model (C-index = 0.719) in the training group. According to the Delong test we chose the Lasso-Cox regression model (P = 0.019) and validated its performance with time-dependent receiver operating characteristics curves(tdROC), calibration curves, and decision curve analysis (DCA). The areas under the tdROC curves for 1, 3, and 5 years were 0.855, 0.888, and 0.924 in the training group and 0.841, 0.871, and 0.901 in the validation group, respectively. The calibration curves performed well, as well as the DCA showed higher net returns and a broader range of threshold probabilities using the predictive model. A nomogram visualization is used to display the results of the selected model. Conclusion: The study established a nomogram based on the Lasso-Cox regression model for predicting recurrence in AC patients. Compared to a nomogram built via other methods, this one is more robust and accurate. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer (THCA) has become a common malignancy in recent years, with the mortality rate steadily increasing. PANoptosis is a unique kind of programmed cell death (PCD), including pyroptosis, necroptosis, and apoptosis, and is involved in the proliferation and prognosis of numerous cancers. This paper demonstrated the connection between PANoptosis-related genes and THCA based on the analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, which have not been evaluated yet. Methods: We identified PANoptosis-related differentially expressed genes (PRDEGs) by multi-analyzing the TCGA-THCA and GEO datasets. To identify the significant PRDEGs, a prognostic model was constructed using least absolute shrinkage and selection operator regression (LASSO). The predictive values of the significant PRDEGs for THCA outcomes were determined using Cox regression analysis and nomograms. Gene enrichment analyses were performed. Finally, immunohistochemistry was carried out using the human protein atlas. Results: A LASSO regression model based on nine PRDEGs was constructed, and the prognostic value of key PRDEGs was explored via risk score. Univariate and multivariate Cox regression were implemented to identify further three significant PRDEGs closely related to distant metastasis, lymph node metastasis, and tumor stage. Then, a nomogram was constructed, which presented high predictive accuracy for 5 years survival of THCA patients. Gene enrichment analyses in THCA were strongly associated with PCD pathways. CASP6 presented significantly differential expression during clinical T stage, N stage, and PFI events (P

Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develop new Treg‐related prognostic biomarkers to monitor the prognosis of patients with gastric cancer (GC). Treg‐related prognostic genes were screened from Treg‐related differentially expressed genes in GC patients by using Cox regression analysis, based on which a prognostic model was constructed. Then, combined with RiskScore, survival curve, survival status assessment and ROC analysis, these genes were used to verify the accuracy of the model, whose independent prognostic ability was also evaluated. Six Treg‐related prognostic genes (CHRDL1, APOC3, NPTX1, TREML4, MCEMP1, GH2) in GC were identified, and a 6‐gene Treg‐related prognostic model was constructed. Survival analysis revealed that patients had a higher survival rate in the low‐risk group. Combining clinicopathological features, we performed univariate and multivariate regression analyses, with results establishing that the RiskScore was an independent prognostic factor. Predicted 1‐, 3‐ and 5‐year survival rates of GC patients had a good fit with the actual survival rates according to nomogram results. In addition patients in the low‐risk group had higher tumour mutational burden (TMB) values. Gene Set Enrichment Analysis (GSEA) demonstrated that genes in the high‐risk group were significantly enriched in pathways related to immune inflammation, tumour proliferation and migration. In general, we constructed a 6‐gene Treg‐associated GC prognostic model with good prediction accuracy, where RiskScore could act as an independent prognostic factor. This model is expected to provide a reference for clinicians to estimate the prognosis of GC patients. [ABSTRACT FROM AUTHOR]

Abstract Objective The incidence of non-virus-related hepatocellular carcinoma (NV-HCC) in hepatocellular carcinoma (HCC) is steadily increasing. The aim of this study was to establish a prognostic model to evaluate the overall survival (OS) of NV-HCC patients. Methods Overall, 261 patients with NV-HCC were enrolled in this study. A prognostic model was developed by using LASSO-Cox regression analysis. The prognostic power was appraised by the concordance index (C-index), and the time-dependent receiver operating characteristic curve (TD-ROC). Kaplan–Meier (K–M) survival analysis was used to evaluate the predictive ability in the respective subgroups stratified by the prognostic model risk score. A nomogram for survival prediction was established by integrating the prognostic model, TNM stage, and treatment. Results According to the LASSO-Cox regression results, the number of nodules, lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), alkaline phosphatase (ALP), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (SLR) and C-reactive protein (CRP) were included for prognostic model construction. The C-index of the prognostic model was 0.759 (95% CI 0.723–0.797) in the development cohort and 0.796 (95% CI 0.737–0.855) in the validation cohort, and its predictive ability was better than TNM stage and treatment. The TD-ROC showed similar results. K–M survival analysis showed that NV-HCC patients with low risk scores had a better prognosis (P

Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified.Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored.Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group.Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.

Purpose: To investigate the risk factors for recurrence in patients with early-stage hepatocellular carcinoma (HCC) after minimally invasive treatment with curative intent, then to construct a prediction model based on Lasso-Cox regression and visualize the model built. Methods: Clinical data were collected from 547 patients that received minimally invasive treatment in our hospital from January 1, 2012, to December 31, 2016. Lasso regression was used to screen risk factors for recurrence. Then we established Cox proportional hazard regression model and random survival forest model including several parameters screened by Lasso regression. An optimal model was selected by comparing the values of C-index, then the model was visualized and the nomogram was finally plotted. Results: The variables screened by Lasso regression including age, gender, cirrhosis, tumor number, tumor size, platelet-albumin-bilirubin index (PALBI), and viral load were incorporated in the Cox model and random survival forest model (P<0.05). The C-index of these two models in the training sets was 0.729 and 0.708, and was 0.726 and 0.700 in the validation sets, respectively. So we finally chose Lasso-Cox regression model, and the calibration curve in the validation set performed well, indicating that the model built has a better predictive ability. And then a nomogram was plotted based on the model chosen to visualize the results. Conclusions: The present study established a nomogram for predicting recurrence in patients with early-stage HCC based on the Lasso-Cox regression model. This nomogram was of some guiding significance for screening populations at high risk of recurrence after treatment, by which doctors can formulate individualized follow-up strategies or treatment protocols according to the predicted risk of relapse for patients to improve the long-term prognosis. [ABSTRACT FROM AUTHOR]

Objective: The incidence of non-virus-related hepatocellular carcinoma (NV-HCC) in hepatocellular carcinoma (HCC) is steadily increasing. The aim of this study was to establish a prognostic model to evaluate the overall survival (OS) of NV-HCC patients. Methods: Overall, 261 patients with NV-HCC were enrolled in this study. A prognostic model was developed by using LASSO-Cox regression analysis. The prognostic power was appraised by the concordance index (C-index), and the time-dependent receiver operating characteristic curve (TD-ROC). Kaplan–Meier (K–M) survival analysis was used to evaluate the predictive ability in the respective subgroups stratified by the prognostic model risk score. A nomogram for survival prediction was established by integrating the prognostic model, TNM stage, and treatment. Results: According to the LASSO-Cox regression results, the number of nodules, lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), alkaline phosphatase (ALP), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (SLR) and C-reactive protein (CRP) were included for prognostic model construction. The C-index of the prognostic model was 0.759 (95% CI 0.723–0.797) in the development cohort and 0.796 (95% CI 0.737–0.855) in the validation cohort, and its predictive ability was better than TNM stage and treatment. The TD-ROC showed similar results. K–M survival analysis showed that NV-HCC patients with low risk scores had a better prognosis (P < 0.05). A nomogram based on the prognostic model, TNM stage, and treatment was constructed with sufficient discriminatory power with C-indexes of 0.78 and 0.85 in the development and validation cohort, respectively. Conclusion: For NV-HCC, this prognostic model could predict an OS benefit for patients, which may assist clinicians in designing individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is a common and serious neurological disease, and multiple pathways of cell apoptosis are implicated in its pathogenesis. Recently, extensive studies have indicated that pyroptosis is involved in various diseases, especially cerebrovascular diseases. However, the exact mechanism of interaction between pyroptosis and IS is scarcely understood. Thus, we aimed to investigate the impact of pyroptosis on ISmediated systemic inflammation. Methods: First, the RNA regulation patterns mediated by 33 pyroptosis-related genes identified in 20 IS samples and 20 matched-control samples were systematically evaluated. Second, a series of bioinformatics algorithms were used to investigate the contribution of PRGs to IS pathogenesis. We determined three composition classifiers of PRGs which potentially distinguished healthy samples from IS samples according to the risk score using single-variable logistic regression, LASSO-Cox regression, and multivariable logistic regression analyses. Third, 20 IS patients were classified by unsupervised consistent cluster analysis in relation to pyroptosis. The association between pyroptosis and systemic inflammation characteristics was explored, which was inclusive of immune reaction gene sets, infiltrating immunocytes and human leukocyte antigen genes. Results: We identified that AIM2, SCAF11, and TNF can regulate immunoinflammatory responses after strokes via the production of inflammatory factors and activation of the immune cells. Meanwhile, we identified distinct expression patterns mediated by pyroptosis and revealed their immune characteristics, differentially expressed genes, signaling pathways, and target drugs. Conclusion: Our findings lay a foundation for further research on pyroptosis and IS systemic inflammation, to improve IS prognosis and its responses to immunotherapy. [ABSTRACT FROM AUTHOR]

The prognosis of patients with recurrent low-grade glioma (rLGG) varies greatly. Some patients can survive more than 10 years after recurrence, while other patients have less than 1 year of survival. In order to identify the related risk factors affecting the prognosis of rLGG patients, we performed a series of bioinformatics analyses on RNA-sequencing data of rLGG based on the CGGA database, and finally constructed a 12-genes prognostic signature, dividing all the rLGG patients into high- and low-risk subgroups. The result showed an excellent predictive effect in both the training cohort and the validation cohort using LASSO-COX regression. Moreover, multivariate COX analysis identified 4 independent prognostic factors of rLGG, and among them, ZCWPW1 is identified as a high-value protective factor. In all, this prognostic model displayed robust predictive capability for the overall survival (OS) of rLGG patients, providing a new monitoring method for rLGG, and the 4 independent prognostic factors, especially ZCWPW1, can be potential targets for rLGG, bringing new possibilities for the treatment of rLGG patients., (Copyright © 2024. Published by Elsevier Inc.)

Background: Disseminated intravascular coagulation (DIC) is a devastating condition, which always cause poor outcome of critically ill patients in intensive care unit. Studies concerning short-term mortality prediction in DIC patients is scarce. This study aimed to identify risk factors contributing to DIC mortality and construct a predictive nomogram., Methods: A total of 676 overt DIC patients were included. A Cox proportional hazards regression model was developed based on covariates identified using least absolute shrinkage and selection operator (LASSO) regression. The prediction performance was independently evaluated in the MIMIC-III and MIMIC-IV Clinical Database, as well as the 908th Hospital Database (908thH). Model performance was independently assessed using MIMIC-III, MIMIC-IV, and the 908th Hospital Clinical Database., Results: The Cox model incorporated variables identified by Lasso regression including heart failure, sepsis, height, SBP, lactate levels, HCT, PLT, INR, AST, and norepinephrine use. The model effectively stratified patients into different mortality risk groups, with a C-index of >0.65 across the MIMIC-III, MIMIC-IV, and 908th Hospital databases. The calibration curves of the model at 7 and 28 days demonstrated that the prediction performance was good. And then, a nomogram was developed to facilitate result visualization. Decision curve analysis indicated superior net benefits of the nomogram., Conclusion: This study provides a predictive nomogram for short-term overt DIC mortality risk based on a Lasso-Cox regression model, offering individualized and reliable mortality risk predictions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zeng, Lin, Zhong, He, Zhang and Song.)

Background: The aim of this research is to establish and validate a prognostic model for predicting prognosis in non-small cell lung cancer (NSCLC) patients with bone metastases. Methods: Overall, 176 NSCLC patients with bone metastases were retrospectively evaluated in the research. We employed the LASSO-Cox regression method to select the candidate indicators for predicting the prognosis among NSCLC patients complicated with bone metastases. We employed the receiver operating characteristic curve (ROC) and the concordance index (C-index) to assess the discriminative ability. Results: Based on the LASSO-Cox regression analysis, 9 candidate indicators were screened to build the prognostic model. The prognostic model had a higher C-index in the training cohort (0.738, 95% CI: 0.680-0.796) and the validation cohort (0.660, 95% CI: 0.566-0.754) than the advanced lung cancer inflammation index (ALI). Furthermore, the AUCs of the 1-, 2-, and 3-year OS predictions for the prognostic model were higher than ALI in both cohorts. Kaplan-Meier curves and the estimated restricted mean survival time (RMST) values showed that the patients in the low-risk subgroup had the lower probabilities of cancer-specific mortality than high-risk subgroup. Conclusions: The prognostic model could provide clinicians with precise information and facilitate individualized treatment for patients with bone metastases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Abstract Background This study evaluated the predictive value of gene signatures for biochemical recurrence (BCR) in primary prostate cancer (PCa) patients. Methods Clinical features and gene expression profiles of PCa patients were attained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, which were further classified into a training set (n = 419), a validation set (n = 403). The least absolute shrinkage and selection operator Cox (LASSO‐Cox) method was used to select discriminative gene signatures in training set for biochemical recurrence‐free survival (BCRFS). Selected gene signatures established a risk score system. Univariate and multivariate analyses of prognostic factors about BCRFS were performed using the Cox proportional hazards regression models. A nomogram based on multivariate analysis was plotted to facilitate clinical application. Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) analyses were then executed for differentially expressed genes (DEGs). Results Notably, the risk score could significantly identify BCRFS by time‐dependent receiver operating characteristic (t‐ROC) curves in the training set (3‐year area under the curve (AUC) = 0.820, 5‐year AUC = 0.809) and the validation set (3‐year AUC = 0.723, 5‐year AUC = 0.733). Conclusions Clinically, the nomogram model, which incorporates Gleason score and the risk score, could effectively predict BCRFS and potentially be utilized as a useful tool for the screening of BCRFS in PCa.

The fatty acid metabolism (FAM) is known to impact tumorigenesis, tumor progression and treatment resistance via enhancing lipid synthesis, storage and catabolism. However, the role of FAM in head and neck squamous cell carcinoma (HNSCC) has remained elusive. In the present study, we obtained a total of 69 differentially expressed FAM-related genes between 502 HNSCC samples and 44 normal samples from The Cancer Genome Atlas (TCGA) database. The HNSCC samples were divided into 2 clusters according to 69 differentially expressed genes (DEGs) via cluster analysis. Then DEGs in the two clusters were found, and 137 prognostic DEGs were identified by univariate analysis. Subsequently, combined with the clinical information of 546 HNSCC patients from TCGA database, a 12-gene prognostic risk model was established (FEPHX3, SPINK7, FCRLA, MASP1, ZNF541, CD5, BEST2 and ZAP70 were down-regulation, ADPRHL1, DYNC1I1, KCNG1 and LINC00460 were up-regulation) using multivariate Cox regression and LASSO regression analysis. The risk scores of 546 HNSCC samples were calculated. According to the median risk score, 546 HNSCC patients were divided into the high- and low-risk (high- and low score) groups. The Kaplan-Meier survival analysis showed that the survival time of HNSCC patients was significantly shorter in the high-risk group than that in the low-risk group (p < 0.001). The same conclusion was obtained in the Gene Expression Omnibus (GEO) dataset. After that, the multivariate Cox regression analysis indicated that the risk score was an independent factor for patients with HNSCC in the TCGA cohort. In addition, single-sample gene set enrichment analysis (ssGSEA) indicated that the level of infiltrating immune cells was relatively low in the high-risk group compared with the low-risk group. In summary , FAM-related gene expression-based risk signature could predict the prognosis of HNSCC independently. [ABSTRACT FROM AUTHOR]

Background: Bladder carcinoma (BLCA) is a common malignant tumor with high morbidity and mortality in the urinary system. Pyroptosis is a pattern of programmed cell death that is closely associated with progression of tumors. Therefore, it is significant to probe the expression of pyroptosis-related genes (PRGs) in BLCA. Methods: The differentially expressed genes in normal and BLCA tissues were first obtained from the Cancer Genome Atlas (TCGA) database analysis, as well as PRGs from the National Center for Biotechnology Information (NCBI) database, intersecting to obtain differentially expressed pyroptosis-related genes (DEPRGs) in BLCA. With the construction of a prognostic model of pyroptosis by regression analysis, we derived and validated key genes, which were ascertained as a separate prognostic marker by individual prognostic and clinical relevance analysis. In addition, we gained six immune cells from the Tumor Immune Evaluation Resource (TIMER) website and analyzed the relationship between pyroptosis prognostic genes and immune infiltration. Result: Our results revealed that 31 DEPRGs were available by comparing normal and BLCA tissues with |log2 (fold change, FC)| > 0.5 and FDR <0.05. Four key genes (CRTAC1, GSDMB, AIM2, and FOXO3) derived from the pyroptosis prognostic model were experimentally validated for consistent expression in BLCA patients. Following risk scoring, the low-risk group of BLCA patients had noticeably higher overall survival (OS) than the high-risk group (p < 0.001). Risk score was still an independent prognostic factor (HR = 1.728, 95% CI =1.289–2.315, p < 0.001). In addition, we found remarkable correlations among the expression of pyroptosis-related prognostic genes and the immune infiltration of CD4+ T cells, CD8+ T cells, B cells, dendritic cells, macrophages, and neutrophils. Conclusion: Genes (CRTAC1, GSDMB, AIM2, and FOXO3) associated with pyroptosis are potential BLCA prognostic biomarkers that act as an essential part in the predictive prognosis of survival and immunotherapy of BLCA. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to identify the most valuable predictors of prognosis in glioblastoma (GBM) patients and develop and validate a nomogram to estimate individualized survival probability. Methods We conducted a real-world retrospective cohort study of 987 GBM patients diagnosed between September 2010 and December 2018. Computer generated random numbers were used to assign patients into a training cohort (694 patients) and internal validation cohort (293 patients). A least absolute shrinkage and selection operator (LASSO)-Cox model was used to select candidate variables for the prediction model. Cox proportional hazards regression was used to estimate overall survival. Models were internally validated using the bootstrap method and generated individualized predicted survival probabilities at 6, 12, and 24 months, which were compared with actual survival. Results The final nomogram was developed using the Cox proportional hazards model, which was the model with best fit and calibration. Gender, age at surgery, extent of tumor resection, radiotherapy, chemotherapy, and IDH1 mutation status were used as variables. The concordance indices for 6-, 12-, 18-, and 24-month survival probabilities were 0.776, 0.677, 0.643, and 0.629 in the training set, and 0.725, 0.695, 0.652, and 0.634 in the validation set, respectively. Conclusions Our nomogram that assesses individualized survival probabilities (6-, 12-, and 24-month) in newly diagnosed GBM patients can assist healthcare providers in optimizing treatment and counseling patients. Trial registration: retrospectively registered.

The fatty acid metabolism (FAM) is known to impact tumorigenesis, tumor progression and treatment resistance via enhancing lipid synthesis, storage and catabolism. However, the role of FAM in head and neck squamous cell carcinoma (HNSCC) has remained elusive. In the present study, we obtained a total of 69 differentially expressed FAM-related genes between 502 HNSCC samples and 44 normal samples from The Cancer Genome Atlas (TCGA) database. The HNSCC samples were divided into 2 clusters according to 69 differentially expressed genes (DEGs) via cluster analysis. Then DEGs in the two clusters were found, and 137 prognostic DEGs were identified by univariate analysis. Subsequently, combined with the clinical information of 546 HNSCC patients from TCGA database, a 12-gene prognostic risk model was established (FEPHX3, SPINK7, FCRLA, MASP1, ZNF541, CD5, BEST2 and ZAP70 were down-regulation, ADPRHL1, DYNC1I1, KCNG1 and LINC00460 were up-regulation) using multivariate Cox regression and LASSO regression analysis. The risk scores of 546 HNSCC samples were calculated. According to the median risk score, 546 HNSCC patients were divided into the high- and low-risk (high- and low score) groups. The Kaplan-Meier survival analysis showed that the survival time of HNSCC patients was significantly shorter in the high-risk group than that in the low-risk group (p < 0.001). The same conclusion was obtained in the Gene Expression Omnibus (GEO) dataset. After that, the multivariate Cox regression analysis indicated that the risk score was an independent factor for patients with HNSCC in the TCGA cohort. In addition, single-sample gene set enrichment analysis (ssGSEA) indicated that the level of infiltrating immune cells was relatively low in the high-risk group compared with the low-risk group. In summary, FAM-related gene expression-based risk signature could predict the prognosis of HNSCC independently.

BackgroundBladder carcinoma (BLCA) is a common malignant tumor with high morbidity and mortality in the urinary system. Pyroptosis is a pattern of programmed cell death that is closely associated with progression of tumors. Therefore, it is significant to probe the expression of pyroptosis-related genes (PRGs) in BLCA.MethodsThe differentially expressed genes in normal and BLCA tissues were first obtained from the Cancer Genome Atlas (TCGA) database analysis, as well as PRGs from the National Center for Biotechnology Information (NCBI) database, intersecting to obtain differentially expressed pyroptosis-related genes (DEPRGs) in BLCA. With the construction of a prognostic model of pyroptosis by regression analysis, we derived and validated key genes, which were ascertained as a separate prognostic marker by individual prognostic and clinical relevance analysis. In addition, we gained six immune cells from the Tumor Immune Evaluation Resource (TIMER) website and analyzed the relationship between pyroptosis prognostic genes and immune infiltration.ResultOur results revealed that 31 DEPRGs were available by comparing normal and BLCA tissues with |log2 (fold change, FC)| > 0.5 and FDR

BackgroundBreast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated.Materials and methodsIn The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs’ consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME).ResultsIn TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results.ConclusionOur data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy.

Background: Thyroid cancer (THCA) has become a common malignancy in recent years, with the mortality rate steadily increasing. PANoptosis is a unique kind of programmed cell death (PCD), including pyroptosis, necroptosis, and apoptosis, and is involved in the proliferation and prognosis of numerous cancers. This paper demonstrated the connection between PANoptosis-related genes and THCA based on the analyses of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, which have not been evaluated yet., Methods: We identified PANoptosis-related differentially expressed genes (PRDEGs) by multi-analyzing the TCGA-THCA and GEO datasets. To identify the significant PRDEGs, a prognostic model was constructed using least absolute shrinkage and selection operator regression (LASSO). The predictive values of the significant PRDEGs for THCA outcomes were determined using Cox regression analysis and nomograms. Gene enrichment analyses were performed. Finally, immunohistochemistry was carried out using the human protein atlas., Results: A LASSO regression model based on nine PRDEGs was constructed, and the prognostic value of key PRDEGs was explored via risk score. Univariate and multivariate Cox regression were implemented to identify further three significant PRDEGs closely related to distant metastasis, lymph node metastasis, and tumor stage. Then, a nomogram was constructed, which presented high predictive accuracy for 5 years survival of THCA patients. Gene enrichment analyses in THCA were strongly associated with PCD pathways. CASP6 presented significantly differential expression during clinical T stage, N stage, and PFI events (P < 0.05 for all) and demonstrated the highest degree of diagnostic efficacy in PRDEGs (HR: 2.060, 95 % CI: 1.170-3.628, P < 0.05). Immunohistochemistry showed CASP6 was more abundant in THCA tumor tissue., Conclusion: A potential prognostic role for PRDEGs in THCA was identified, providing a new direction for treatment. CASP6 may be a potential therapeutic target and a novel prognostic biomarker for THCA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: To analyze the risk factors affecting recurrence in early-stage hepatocellular carcinoma (HCC) patients treated with ablation and then establish a nomogram to provide a clear and accessible representation of the patients' recurrence risk., Methods: Collect demographic and clinical data of 898 early-stage HCC patients who underwent ablation treatment at Beijing You'an Hospital, affiliated with Capital Medical University from January 2014 to December 2022. Patients admitted from 2014 to 2018 were included in the training cohort, while 2019 to 2022 were in the validation cohort. Lasso and Cox regression was used to screen independent risk factors for HCC patients recurrence, and a nomogram was then constructed based on the screened factors., Results: Age, gender, Barcelona Clinic Liver Cancer (BCLC) stage, tumor size, globulin (Glob) and γ-glutamyl transpeptidase (γ-GT) were finally incorporated in the nomogram for predicting the recurrence-free survival (RFS) of patients. We further confirmed that the nomogram has optimal discrimination, consistency and clinical utility by the C-index, Receiver Operating Characteristic Curve (ROC), calibration curve and Decision Curve Analysis (DCA). Moreover, we divided the patients into different risk groups and found that the nomogram can effectively identify the high recurrence risk patients by the Kaplan-Meier curves., Conclusion: This study developed a nomogram using Lasso-Cox regression to predict RFS in early-stage HCC patients following ablation, aiding clinicians in identifying high-risk groups for personalized follow-up treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Sheng, Qiao, Sun and Jin.)

Background: This study evaluated the predictive value of gene signatures for biochemical recurrence (BCR) in primary prostate cancer (PCa) patients. Methods: Clinical features and gene expression profiles of PCa patients were attained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, which were further classified into a training set (n = 419), a validation set (n = 403). The least absolute shrinkage and selection operator Cox (LASSO‐Cox) method was used to select discriminative gene signatures in training set for biochemical recurrence‐free survival (BCRFS). Selected gene signatures established a risk score system. Univariate and multivariate analyses of prognostic factors about BCRFS were performed using the Cox proportional hazards regression models. A nomogram based on multivariate analysis was plotted to facilitate clinical application. Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) analyses were then executed for differentially expressed genes (DEGs). Results: Notably, the risk score could significantly identify BCRFS by time‐dependent receiver operating characteristic (t‐ROC) curves in the training set (3‐year area under the curve (AUC) = 0.820, 5‐year AUC = 0.809) and the validation set (3‐year AUC = 0.723, 5‐year AUC = 0.733). Conclusions: Clinically, the nomogram model, which incorporates Gleason score and the risk score, could effectively predict BCRFS and potentially be utilized as a useful tool for the screening of BCRFS in PCa. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori, a primary carcinogen, and also in response to chemotherapy drugs. However, the prognostic evaluation of GC to pyroptosis is insufficient. Consensus clustering by pyroptosis-related regulators was used to classify 618 patients with GC from four GEO cohorts. Following Cox regression with differentially expressed genes, our prognosis model (PS-score) was built by LASSO-Cox analysis. The TCGA-STAD cohort was used as the validation set. ESTIMATE, CIBERSORTx, and EPIC were used to investigate the tumor microenvironment (TME). Immunotherapy cohorts by blocking PD1/PD-L1 were used to investigate the treatment response. The subtyping of GC based on pyroptosis-related regulators was able to classify patients according to different clinical traits and TME. The difference between the two subtypes identified in this study was used to develop a prognosis model which we named “PS-score.” The PS-score could predict the prognosis of patients with GC and his/her overall survival time. A low PS-score implies greater inflammatory cell infiltration and better response of immunotherapy by PD1/PD-L1 blockers. Our findings provide a foundation for future research targeting pyroptosis and its immune microenvironment to improve prognosis and responses to immunotherapy.

Background: This study aimed to identify the most valuable predictors of prognosis in glioblastoma (GBM) patients and develop and validate a nomogram to estimate individualized survival probability.Methods: We conducted a real-world retrospective cohort study of 987 GBM patients diagnosed between September 2010 and December 2018. Computer generated random numbers were used to assign patients into a training cohort (694 patients) and internal validation cohort (293 patients). A least absolute shrinkage and selection operator (LASSO)-Cox model was used to select candidate variables for the prediction model. Cox proportional hazards regression was used to estimate overall survival. Models were internally validated using the bootstrap method and generated individualized predicted survival probabilities at 6, 12, and 24 months, which were compared with actual survival.Results: The final nomogram was developed using the Cox proportional hazards model, which was the model with best fit and calibration. Gender, age at surgery, extent of tumor resection, radiotherapy, chemotherapy, and IDH1 mutation status were used as variables. The concordance indices for 6-, 12-, 18-, and 24-month survival probabilities were 0.776, 0.677, 0.643, and 0.629 in the training set, and 0.725, 0.695, 0.652, and 0.634 in the validation set, respectively.Conclusions: Our nomogram that assesses individualized survival probabilities (6-, 12-, and 24-month) in newly diagnosed GBM patients can assist healthcare providers in optimizing treatment and counseling patients.Trial Registration: retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified. Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored. Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group. Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Guo, Shang, Cui, Zhou, Sun, Fu, Zhang, Feng and Chen.)

Purpose: To investigate the risk factors for recurrence in patients with early-stage hepatocellular carcinoma (HCC) after minimally invasive treatment with curative intent, then to construct a prediction model based on Lasso-Cox regression and visualize the model built., Methods: Clinical data were collected from 547 patients that received minimally invasive treatment in our hospital from January 1, 2012, to December 31, 2016. Lasso regression was used to screen risk factors for recurrence. Then we established Cox proportional hazard regression model and random survival forest model including several parameters screened by Lasso regression. An optimal model was selected by comparing the values of C-index, then the model was visualized and the nomogram was finally plotted., Results: The variables screened by Lasso regression including age, gender, cirrhosis, tumor number, tumor size, platelet-albumin-bilirubin index (PALBI), and viral load were incorporated in the Cox model and random survival forest model (P<0.05). The C-index of these two models in the training sets was 0.729 and 0.708, and was 0.726 and 0.700 in the validation sets, respectively. So we finally chose Lasso-Cox regression model, and the calibration curve in the validation set performed well, indicating that the model built has a better predictive ability. And then a nomogram was plotted based on the model chosen to visualize the results., Conclusions: The present study established a nomogram for predicting recurrence in patients with early-stage HCC based on the Lasso-Cox regression model. This nomogram was of some guiding significance for screening populations at high risk of recurrence after treatment, by which doctors can formulate individualized follow-up strategies or treatment protocols according to the predicted risk of relapse for patients to improve the long-term prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qiao, Zhang, Liu, Li, Zang, Mei, Zheng and Zhang.)

Background: Ischemic stroke (IS) is a common and serious neurological disease, and multiple pathways of cell apoptosis are implicated in its pathogenesis. Recently, extensive studies have indicated that pyroptosis is involved in various diseases, especially cerebrovascular diseases. However, the exact mechanism of interaction between pyroptosis and IS is scarcely understood. Thus, we aimed to investigate the impact of pyroptosis on IS-mediated systemic inflammation. Methods: First, the RNA regulation patterns mediated by 33 pyroptosis-related genes identified in 20 IS samples and 20 matched-control samples were systematically evaluated. Second, a series of bioinformatics algorithms were used to investigate the contribution of PRGs to IS pathogenesis. We determined three composition classifiers of PRGs which potentially distinguished healthy samples from IS samples according to the risk score using single-variable logistic regression, LASSO-Cox regression, and multivariable logistic regression analyses. Third, 20 IS patients were classified by unsupervised consistent cluster analysis in relation to pyroptosis. The association between pyroptosis and systemic inflammation characteristics was explored, which was inclusive of immune reaction gene sets, infiltrating immunocytes and human leukocyte antigen genes. Results: We identified that AIM2, SCAF11, and TNF can regulate immuno-inflammatory responses after strokes via the production of inflammatory factors and activation of the immune cells. Meanwhile, we identified distinct expression patterns mediated by pyroptosis and revealed their immune characteristics, differentially expressed genes, signaling pathways, and target drugs. Conclusion: Our findings lay a foundation for further research on pyroptosis and IS systemic inflammation, to improve IS prognosis and its responses to immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Zhang, Qu, Tang, Qu, Wen, Sun and Pan.)

Background: Breast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated., Materials and Methods: In The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs' consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME)., Results: In TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results., Conclusion: Our data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Wang, Li, Zhang, Chen and Li.)

Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori , a primary carcinogen, and also in response to chemotherapy drugs. However, the prognostic evaluation of GC to pyroptosis is insufficient. Consensus clustering by pyroptosis-related regulators was used to classify 618 patients with GC from four GEO cohorts. Following Cox regression with differentially expressed genes, our prognosis model (PS-score) was built by LASSO-Cox analysis. The TCGA-STAD cohort was used as the validation set. ESTIMATE, CIBERSORTx, and EPIC were used to investigate the tumor microenvironment (TME). Immunotherapy cohorts by blocking PD1 / PD-L1 were used to investigate the treatment response. The subtyping of GC based on pyroptosis-related regulators was able to classify patients according to different clinical traits and TME. The difference between the two subtypes identified in this study was used to develop a prognosis model which we named "PS-score." The PS-score could predict the prognosis of patients with GC and his/her overall survival time. A low PS-score implies greater inflammatory cell infiltration and better response of immunotherapy by PD1 / PD-L1 blockers. Our findings provide a foundation for future research targeting pyroptosis and its immune microenvironment to improve prognosis and responses to immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shao, Yang, Fu, Zheng, Liu, Chai and Jia.)