scholarly journals Identification of Prognostic Immune-Related Genes by Integrating mRNA Expression and Methylation in Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Jie Zhu ◽  
Min Wang ◽  
Daixing Hu
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Risk Groups ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Cpg Site ◽  
Risk Patients ◽  
Immune Related Genes ◽  
Geo Database

Background. There is plenty of evidence showing that immune-related genes (IRGs) and epigenetic modifications play important roles in the biological process of cancer. The purpose of this study is to establish novel IRG prognostic markers by integrating mRNA expression and methylation in lung adenocarcinoma (LUAD). Methods and Results. The transcriptome profiling data and the RNA-seq data of LUAD with the corresponding clinical information of 543 LUAD cases were downloaded from The Cancer Genome Atlas (TCGA) database, which were analyzed by univariate Cox proportional regression and multivariate Cox proportional regression to develop an independent prognostic signature. On the basis of this signature, we could divide LUAD patients into the high-risk, medium-risk, and low-risk groups. Further survival analyses demonstrated that high-risk patients had significantly shorter overall survival (OS) than low-risk patients. The signature, which contains 8 IRGs (S100A16, FGF2, IGKV4-1, CX3CR1, INHA, ANGPTL4, TNFRSF11A, and VIPR1), was also validated by data from the Gene Expression Omnibus (GEO) database. We also conducted analyses of methylation levels of the relevant IRGs and their CpG sites. Meanwhile, their associations with prognosis were examined and validated by the GEO database, revealing that the methylation levels of INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 may be used as the potential regulators for the treatment of LUAD. Conclusion. Collectively, INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 are promising biomarkers for monitoring the outcomes of LUAD.

scholarly journals Four long noncoding RNAs act as biomarkers in lung adenocarcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 660-671
Author(s):  
Zhihui Zhang ◽  
Liu Yang ◽  
Yujiang Li ◽  
Yunfei Wu ◽  
Xiang Li ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Noncoding Rna ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Test Set ◽  
Stratified Analysis

Abstract Introduction Lung adenocarcinoma (LUAD) is currently one of the most common malignant tumors worldwide. However, there is a lack of long noncoding RNA (lncRNA)-based effective markers for predicting the prognosis of LUAD patients. We identified four lncRNAs that can effectively predict the prognosis of LUAD patients. Methods We used data gene expression profile for 446 patients from The Cancer Genome Atlas database. The patients were randomly divided into a training set and a test set. Significant lncRNAs were identified by univariate regression. Then, multivariate regression was used to identify lncRNAs significantly associated with the survival rate. We constructed four-lncRNA risk formulas for LUAD patients and divided patients into high-risk and low-risk groups. Identified lncRNAs subsequently verified in the test set, and the clinical independence of the lncRNA model was evaluated by stratified analysis. Then mutated genes were identified in the high-risk and low-risk groups. Enrichment analysis was used to determine the relationships between lncRNAs and co-expressed genes. Finally, the accuracy of the model was verified using external database. Results A four-lncRNA signature (AC018629.1, AC122134.1, AC119424.1, and AL138789.1) has been verified in the training and test sets to be significantly associated with the overall survival of LUAD patients. Conclusions The present study demonstrated that identified four-lncRNA signature can be used as an independent prognostic biomarker for the prediction of survival of LUAD patients.

scholarly journals A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Cells ◽  
Prognostic Model ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Performance ◽  
Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

scholarly journals Prophylaxis of venous thromboembolism in general surgery: guidelines differ and we still need local policies

2011 ◽  
Vol 93 (5) ◽  
pp. 370-374
Author(s):  
D Veeramootoo ◽  
L Harrower ◽  
R Saunders ◽  
D Robinson ◽  
WB Campbell
Keyword(s):  
At Risk ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Vte Prophylaxis ◽  
Risk Patients ◽  
Local Policies ◽  
One Year ◽  
The Uk

INTRODUCTION Venous thromboembolism (VTE) prophylaxis has become a major issue for surgeons both in the UK and worldwide. Sev-eral different sources of guidance on VTE prophylaxis are available but these differ in design and detail. METHODS Two similar audits were performed, one year apart, on the VTE prophylaxis prescribed for all general surgical inpatients during a single week (90 patients and 101 patients). Classification of patients into different risk groups and compliance in prescribing prophylaxis were examined using different international, national and local guidelines. RESULTS There were significant differences between the numbers of patients in high, moderate and low-risk groups according to the different guidelines. When groups were combined to indicate simply ‘at risk’ or ‘not at risk’ (in the manner of one of the guidelines), then differences were not significant. Our compliance improved from the first audit to the second. Patients at high risk received VTE prophylaxis according to guidance more consistently than those at low risk. CONCLUSIONS Differences in guidance on VTE prophylaxis can affect compliance significantly when auditing practice, depending on the choice of ‘gold standard’. National guidance does not remove the need for clear and detailed local policies. Making decisions about policies for lower-risk patients can be more difficult than for those at high risk.

scholarly journals The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2657-2664 ◽  
Author(s):  
Bart L. Scott ◽  
Ted A. Gooley ◽  
Mohamed L. Sorror ◽  
Andrew R. Rezvani ◽  
Michael L. Linenberger ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Scoring System ◽  
Hematopoietic Cell Transplantation ◽  
Risk Groups ◽  
Hematopoietic Cell ◽  
Low Risk ◽  
International Prognostic Scoring System ◽  
High Risk Disease ◽  
Risk Patients

Abstract Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

scholarly journals Metabolic syndrome related gene signature predicts the prognosis of patients with pancreatic ductal carcinoma. A novel link between metabolic dysregulation and pancreatic ductal carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weiyang Cai ◽  
Wenming Bao ◽  
Shengwei Chen ◽  
Yan Yang ◽  
Yanyan Li
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cox Regression ◽  
Ductal Carcinoma ◽  
Risk Groups ◽  
Cancer Genome ◽  
Low Risk ◽  
Pancreatic Ductal Carcinoma ◽  
Blue Module ◽  
Geo Database

Abstract Background Pancreatic cancer is one of the most common malignancies worldwide. In recent years, specific metabolic activities, which involves the development of tumor, caused wide public concern. In this study, we wish to explore the correlation between metabolism and progression of tumor. Methods A retrospective analysis including 95 patients with pancreatic ductal adenocarcinoma (PDAC) and PDAC patients from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), and The Gene Expression Omnibus (GEO) database were involved in our study. Multivariate Cox regression analysis was used to construct the prognosis model. The potential connection between metabolism and immunity of PDAC was investigated through a weighted gene co-expression network analysis (WGCNA). 22 types of Tumor-infiltrating immune cells (TIICs) between high-risk and low-risk groups were estimated through CIBERSORT. Moreover, the potential immune-related signaling pathways between high-risk and low-risk groups were explored through the gene set enrichment analysis (GSEA). The role of key gene GMPS in developing pancreatic tumor was further investigated through CCK-8, colony-information, and Transwell. Results The prognostic value of the MetS factors was analyzed using the Cox regression model, and a clinical MetS-based nomogram was established. Then, we established a metabolism-related signature to predict the prognosis of PDAC patients based on the TCGA databases and was validated in the ICGC database and the GEO database to find the distinct molecular mechanism of MetS genes in PDAC. The result of WGCNA showed that the blue module was associated with risk score, and genes in the blue module were found to be enriched in the immune-related signaling pathway. Furthermore, the result of CIBERSORT demonstrated that proportions of T cells CD8, T cells Regulatory, Tregs NK cells Activated, Dendritic cells Activated, and Mast cells Resting were different between high-risk and low-risk groups. These differences are potential causes of different prognoses of PDAC patients. GSEA and the protein–protein interaction network (PPI) further revealed that our metabolism-related signature was significantly enriched in immune‐related biological processes. Moreover, knockdown of GMPS in PDAC cells suppressed proliferation, migration, and invasion of tumor cells, whereas overexpression of GMPS performed oppositely. Conclusion The results shine light on fundamental mechanisms of metabolic genes on PDAC and establish a reliable and referable signature to evaluate the prognosis of PDAC. GMPS was identified as a potential candidate oncogene with in PDAC, which can be a novel biomarker and therapeutic target for PDAC treatment.

scholarly journals Rituximab Maintenance Benefits Less for Follicular Lymphoma Patients with Low Risk of the Follicular Lymphoma International Index

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3544-3544
Author(s):  
Tingyu Wang ◽  
Ru Li ◽  
Rui Lv ◽  
Ying Yu ◽  
Jiawen Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Low Risk ◽  
Control Group ◽  
Intermediate Risk ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Risk Patients

Abstract Background Follicular lymphoma (FL) is an incurable indolent disease with a heterogeneous course. The Follicular Lymphoma International Prognostic Index (FLIPI) is the most commonly used prognostic system to predict survival. Rituximab-based immunochemotherapy is now the standard choice for the first-line therapy of FL, followed by rituximab maintenance (RM) in patients with response, which prolongs the progression-free survival (PFS). However, the role of RM in different FLIPI risk groups has never been studied as we know. In this study, we aimed to illustrate the effect of RM in FLIPI risk groups. Methods Newly diagnosed FL patients at our center were enrolled in this analysis. All the patients received the rituximab-based chemoimmunotherapy induction regimens. Response assessments were determined according to Lugano's 2014 criteria. Patients who didn't respond to induction were excluded. Categorical variables were compared using Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results From May 2003 to September 2020, 203 newly diagnosed FL were included. 192 patients (95.0%) achieved remission (complete response, CR/partial response, PR) after immunochemotherapy induction, of whom 96 patients continued rituximab maintenance therapies every 3 months for 1-2 years (RM group) (median 7 times，range 4 to 12). 96 patients received no maintenance or fewer than 4 times (control group) (median 0 times, range 0-3). There were no significant differences in baseline characteristics other than the Ann Arbor stage and pathological grade. The RM group patients were more likely to be at low grade (71.8% vs 54.9%, P = 0.042) and advanced stage (90.6% vs 78.7% , P = 0.027) (Table 1). After a median follow-up of 36.4 months (95% confidence interval [CI], 32.2 to 40.6), median OS and PFS were not reached. The 5-year OS rates and PFS rates were 95.1% (95%CI, 90.2%-100%) and 83.0% (95%CI, 75%-91%)(Fig 1). And RM significantly prolonged the PFS, with 5-year PFS rates 92.2% (95%CI, 85.1%-99.3%) and 70.3%(95%CI, 55%-85.6%) (P = 0.0003) (Fig 2). According to FLIPI risk stratification, patients were classified into low-risk, intermediate-risk, and high-risk groups. The 5-year PFS rates were 97.7% (95%CI, 93.2%-100%), 84.7% (95%CI, 70.4%-99%), and 67.8% (95%CI, 49%-86.6%), respectively (Fig 3). For low-risk patients, there was no significant difference in PFS for the RM group vs the control group. However, for both intermediate risk and high-risk patients, PFS was significantly longer in the RM group compared to the control group (P < 0.0001). The PFS rates at 5 years in intermediate-risk patients were 100% and 77.8% (95%CI, 40.8%-92.6%), for the RM group vs control group, high risk 76.4% (95%CI, 54.3%-98.5%), and 54.9% (95%CI, 21.6%-88.2%), respectively (Fig 4). Conclusion Standard rituximab maintenance significantly prolongs progression-free survival in FLIPI intermediate risk and high-risk patients with FL, but not in the FLIPI low risk group. Figure 1 Figure 1. Disclosures Wang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

scholarly journals Hypoxia-Related Long Non-Coding RNA Signature Predicts the Prognosis of Breast Cancer

2021 ◽  
Author(s):  
Jinlong Huo ◽  
Shuang Shen ◽  
Chen Chen ◽  
Rui Qu ◽  
Youming Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Cytolytic Activity ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

Abstract Background: Breast cancer(BC) is the most common tumour in women. Hypoxia stimulates metastasis in cancer and is linked to poor patient prognosis.Methods: We screened prognostic-related lncRNAs(Long Non-Coding RNAs) from the Cancer Genome Atlas (TCGA) data and constructed a prognostic signature based on hypoxia-related lncRNAs in BC.Results: We identified 21 differentially expressed lncRNAs associated with BC prognosis. Kaplan Meier survival analysis indicated a significantly worse prognosis for the high-risk group(P<0.001). Moreover, the ROC-curve (AUC) of the lncRNAs signature was 0.700, a performance superior to other traditional clinicopathological characteristics. Gene set enrichment analysis (GSEA) showed many immune and cancer-related pathways and in the low-risk group patients. Moreover, TCGA revealed that functions including activated protein C (APC)co-inhibition, Cinnamoyl CoA reductase(CCR),check-point pathways, cytolytic activity, human leukocyte antigen (HLA), inflammation-promotion, major histocompatibility complex(MHC) class1, para-inflammation, T cell co-inhibition, T cell co-stimulation, and Type Ⅰ and Ⅱ Interferons (IFN) responses were significantly different in the low-risk and high-risk groups. Immune checkpoint molecules such as ICOS, IDO1, TIGIT, CD200R1, CD28, PDCD1(PD-1), were also expressed differently between the two risk groups. The expression of m6A-related mRNA indicated that YTHDC1, RBM15, METTL3, and FTO were significantly between the high and low-risk groups.Additionally, immunotherapy in patients with BC from the low-risk group yielded a higher frequency of clinical responses to anti-PD-1/PD-L1 therapy or a combination of anti-PD-1/PD-L1and anti-CTLA4 therapies.Except for lapatinib, the results also show that a high-risk score is related to a higher half-maximal inhibitory concentration (IC50) of chemotherapy drugs.Conclusion: A novel hypoxia-related lncRNAs signature may serve as a prognostic model for BC.

scholarly journals A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic

2020 ◽  
Author(s):  
Benjamin Patterson ◽  
Michael Marks ◽  
Gemma Martinez-Garcia ◽  
Gabriella Bidwell ◽  
Akish Luintel ◽  
...  
Keyword(s):  
High Risk ◽  
Severe Disease ◽  
Risk Groups ◽  
Low Risk ◽  
Infection Prevention And Control ◽  
High Likelihood ◽  
Patients At Risk ◽  
Risk Patients ◽  
Hospital Acquired ◽  
And Control

Introduction The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. Methods We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. Results 93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients. Discussion Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.

scholarly journals Identification of an Immune-Related Risk Signature Correlates With Immunophenotype and Predicts Anti-PD-L1 Efficacy of Urothelial Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Pengju Li ◽  
Shihui Hao ◽  
Yongkang Ye ◽  
Jinhuan Wei ◽  
Yiming Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Urothelial Cancer ◽  
Cox Regression ◽  
Risk Group ◽  
Risk Groups ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Related Risk ◽  
Metastatic Urothelial Cancer

Immune checkpoint inhibitor (ICI) treatment has been used to treat advanced urothelial cancer. Molecular markers might improve risk stratification and prediction of ICI benefit for urothelial cancer patients. We analyzed 406 cases of bladder urothelial cancer from The Cancer Genome Atlas (TCGA) data set and identified 161 messenger RNAs (mRNAs) as differentially expressed immunity genes (DEIGs). Using the LASSO Cox regression model, an eight-mRNA-based risk signature was built. We validated the prognostic and predictive accuracy of this immune-related risk signature in 348 metastatic urothelial cancer (mUC) samples treated with anti-PD-L1 (atezolizumab) from IMvigor210. We built an immune-related risk signature based on the eight mRNAs: ANXA1, IL22, IL9R, KLRK1, LRP1, NRG3, SEMA6D, and STAP2. The eight-mRNA-based risk signature successfully categorizes patients into high-risk and low-risk groups. Overall survival was significantly different between these groups, regardless if the initial TCGA training set, the internal TCGA testing set, all TCGA set, or the ICI treatment set. The hazard ratio (HR) of the high-risk group to the low-risk group was 3.65 (p &lt; 0.0001), 2.56 (p &lt; 0.0001), 3.36 (p &lt; 0.0001), and 2.42 (p = 0.0009). The risk signature was an independent prognostic factor for prediction survival. Moreover, the risk signature was related to immunity characteristics. In different tumor mutational burden (TMB) subgroups, it successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome. Our eight-mRNA-based risk signature is a stable biomarker for urothelial cancer and might be able to predict which patients benefit from ICI treatment. It might play a role in precision individualized immunotherapy.

scholarly journals A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Junyu Huo ◽  
Jinzhen Cai ◽  
Ge Guan ◽  
Huan Liu ◽  
Liqun Wu
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Molecular Subtype ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Type I ◽  
Immune Microenvironment ◽  
Risk Patients

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis.Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups.Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score.Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.

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