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

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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Impact of Stratification of Comorbidities on Nutrition Indices and Survival in Patients on Continuous Ambulatory Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.1177/089686080902902s30 ◽

2009 ◽

Vol 29 (2_suppl) ◽

pp. 153-157 ◽

Cited By ~ 3

Author(s):

Narayan Prasad ◽

Amit Gupta ◽

Archana Sinha ◽

Anurag Singh ◽

Raj Kumar Sharma ◽

...

Keyword(s):

Peritoneal Dialysis ◽

High Risk ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Comorbid Illness ◽

Medium Risk ◽

Risk Patients

Background Case-mix comorbidities and malnutrition influence outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In the present study, we analyzed the influence of stratified comorbidities on nutrition indices and survival in CAPD patients. Patients and Methods We categorized 373 CAPD patients (197 with and 176 without diabetes) into three risk groups: low—age under 70 years and no comorbid illness; medium—age 70 – 80 years, or any age with 1 comorbid illness, or age under 70 years with diabetes; high—age over 80 years, or any age with 2 comorbid illnesses. We then compared nutrition indices and malnutrition by subjective global assessment (SGA) between the three groups. Survival was compared using Kaplan–Meier survival analysis. Results Mean daily calorie and protein intakes in the low-risk group (21 ± 6.7 Kcal/kg, 0.85 ± 0.28 g/kg) were significantly higher than in the medium- (17.6 ± 5.2 Kcal/kg, 0.79 ± 0.25 g/kg) and high-risk (17.5 ± 6.1 Kcal/kg, 0.78 ± 0.26 g/kg) groups ( p = 0.001 and p = 0.04 respectively). Relative risk (RR) of malnutrition was less in the low-risk group (103/147, 70.06%) than in the medium-risk group [135/162, 83.3%; RR: 2.0; 95% confidence interval (CI): 2.1 to 3.4; p = 0.01] or the high-risk group (54/64, 84.4%; RR: 2.3; 95% CI: 2.1 to 4.9; p = 0.03). Mean survivals of patients in the low-, medium-, and high-risk groups were 51 patient–months (95% CI: 45.6 to 56.4 patient–months), 43.3 patient–months (95% CI: 37.8 to 48.7 patient–months), and 29.7 patient–months (95% CI: 23 to 36.4 patient–months) respectively (log-rank: 35.9 patient–months; p = 0.001). The 1-, 2-, 3-, 4-, and 5-year patient survivals in the low-, medium-, and high-risk groups were 96%, 87%, 79%, 65%, and 56%; 89%, 67%, 54%, 43%, and 34%; and 76%, 48%, 31%, 30%, and 30% respectively. Conclusions Intake of calories and protein was significantly lower in the medium-risk and high-risk groups than in the low-risk group. Survival was significantly better in low-risk patients than in medium- and high-risk patients.

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A novel hyperinflammation clinical risk tool, HI5-NEWS2, predicts mortality following early dexamethasone use in an observational cohort of hospitalised COVID-19 patients.

10.1101/2021.06.16.21259011 ◽

2021 ◽

Author(s):

Michael R Ardern-Jones ◽

Hang T.T. Phan ◽

Florina Borca ◽

Matthew Stammers ◽

James Batchelor ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Dexamethasone Treatment ◽

Dexamethasone Therapy ◽

Risk Patients ◽

Anti Inflammatory

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

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Construction of a Prognostic Model Related to Ferroptosis and Iron-Metabolism and the Relationship with the Immune Microenvironment of Gastric Cancer

10.21203/rs.3.rs-708494/v1 ◽

2021 ◽

Author(s):

Fang Wen ◽

Xiaoxue Chen ◽

Wenjie Huang ◽

Shuai Ruan ◽

Suping Gu ◽

...

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Iron Metabolism ◽

Risk Model ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Immune Microenvironment

Abstract Background: The diagnosis rate and mortality of gastric cancer (GC) are among the highest in the global, so it is of great significance to predict the survival time of GC patients. Ferroptosis and iron-metabolism make a critical impact on tumor development and are closely linked to the treatment of cancer and the prognosis of patients. However, the predictive value of the genes involved in ferroptosis and iron-metabolism in GC and their effects on immune microenvironment remain to be further clarified.Methods: In this study, the RNA sequence information and general clinical indicators of GC patients were acquired from the public databases. We first systematically screen out 134 DEGs and 13 PRGs related to ferroptosis and iron-metabolism. Then, we identified six PRDEGs (GLS2, MTF1, SLC1A5, SP1, NOX4, and ZFP36) based on the LASSO-penalized Cox regression analysis. The 6-gene prognostic risk model was established in the TCGA cohort and the GC patients were separated into the high- and the low-risk groups through the risk score median value. GEO cohort was used for verification. The expression of PRDEGs was verified by quantitative QPCR.Results: Our study demonstrated that patients in the low-risk group had a higher survival probability compared with those in high-risk group. In addition, univariate and multivariate Cox regression analyses confirmed that the risk score was an independent prediction parameter. The ROC curve analysis and nomogram manifested that the risk model had the high predictive ability and was more sensitive than general clinical features. Furthermore, compared with the high-risk group, the low-risk group had higher TMB and a longer 5-year survival period. In the immune microenvironment of GC, there were also differences in immune function and highly infiltrated immune cells between the two risk groups.Conclusions: The prognostic risk model based on the six genes associated with ferroptosis and iron-metabolism has a good performance for predicting the prognosis of patients with GC. The treatment of cancer by inducing tumor ferroptosis or mediating tumor iron-metabolism, especially combined with immunotherapy, provides a new possibility for individualized treatment of GC patients.

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CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.653240 ◽

2021 ◽

Vol 9 ◽

Author(s):

Depei Li ◽

Wanming Hu ◽

Xiaoping Lin ◽

Ji Zhang ◽

Zhenqiang He ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Risk Group ◽

Penalized Regression ◽

High Risk Group ◽

Low Risk ◽

Wild Type ◽

Immune Microenvironment ◽

Molecular Features ◽

The Impact

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

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Immune-Related LncRNAs Affect the Prognosis of Osteosarcoma, Which Are Related to the Tumor Immune Microenvironment

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.731311 ◽

2021 ◽

Vol 9 ◽

Author(s):

Qingshan Huang ◽

Yilin Lin ◽

Chenglong Chen ◽

Jingbing Lou ◽

Tingting Ren ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Immune Escape ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

Background: Abnormal expression of lncRNA is closely related to the occurrence and metastasis of osteosarcoma. The tumor immune microenvironment (TIM) is considered to be an important factor affecting the prognosis and treatment of osteosarcoma. This study aims to explore the effect of immune-related lncRNAs (IRLs) on the prognosis of osteosarcoma and its relationship with the TIM.Methods: Ninety-five osteosarcoma samples from the TARGET database were included. Iterative LASSO regression and multivariate Cox regression analysis were used to screen the IRLs signature with the optimal AUC. The predict function was used to calculate the risk score and divide osteosarcoma into a high-risk group and low-risk group based on the optimal cut-off value of the risk score. The lncRNAs in IRLs signature that affect metastasis were screened for in vitro validation. Single sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were used to evaluate the role of TIM in the influence of IRLs on osteosarcoma prognosis.Results: Ten IRLs constituted the IRLs signature, with an AUC of 0.96. The recurrence and metastasis rates of osteosarcoma in the high-risk group were higher than those in the low-risk group. In vitro experiments showed that knockdown of lncRNA (AC006033.2) could increase the proliferation, migration, and invasion of osteosarcoma. ssGSEA and ESTIMATE results showed that the immune cell content and immune score in the low-risk group were generally higher than those in the high-risk group. In addition, the expression levels of immune escape-related genes were higher in the high-risk group.Conclusion: The IRLs signature is a reliable biomarker for the prognosis of osteosarcoma, and they alter the prognosis of osteosarcoma. In addition, IRLs signature and patient prognosis may be related to TIM in osteosarcoma. The higher the content of immune cells in the TIM of osteosarcoma, the lower the risk score of patients and the better the prognosis. The higher the expression of immune escape-related genes, the lower the risk score of patients and the better the prognosis.

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Ferroptosis-Related lncRNA Signature Predicts Prognosis and Immunotherapy Efficacy in Cutaneous Melanoma

10.21203/rs.3.rs-1261242/v1 ◽

2022 ◽

Author(s):

Yujian Xu ◽

Youbai Chen ◽

Zehao Niu ◽

Zheng Yang ◽

Jiahua Xing ◽

...

Keyword(s):

T Cells ◽

High Risk ◽

Risk Score ◽

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

High Risk Group ◽

Low Risk

Abstract Ferroptosis-related lncRNAs are promising biomarkers for predicting the prognosis of many cancers. However, a ferroptosis-related signature to predict the prognosis of cutaneous melanoma (CM) has not been identified. The purpose of our study was to construct a ferroptosis-related lncRNA signature to predict prognosis and immunotherapy efficacy in CM. Ferroptosis-related differentially expressed genes (FDEGs) and lncRNAs (FDELs) were identified using TCGA, GTEx, and FerrDb datasets. We performed Cox and LASSO regressions to identify key FDELs, and constructed a risk score to stratify patients into high- and low-risk groups. A nomogram was developed for clinical use. We performed gene set enrichment analyses (GSEA) to identify significantly enriched pathways. Differences in the tumor microenvironment (TME) between the 2 groups were assessed using 7 algorithms. To predict the efficacy of immune checkpoint inhibitors (ICI), we analyzed the association between PD1 and CTLA4 expression and the risk score. Finally, differences in Tumor Mutational Burden (TMB) and molecular drugs Sensitivity between the 2 groups were performed. Here, we identified 5 lncRNAs (AATBC, AC145423.2, LINC01871, AC125807.2, and AC245041.1) to construct the risk score. The AUC of the lncRNA signature was 0.743 in the training cohort and was validated in the testing and entire cohorts. Kaplan-Meier analyses revealed that the high-risk group had poorer prognosis. Multivariate Cox regression showed that the lncRNA signature was an independent predictor of OS with higher accuracy than traditional clinicopathological features. The 1-, 3-, and 5-year survival probabilities for CM patients were 92.7%, 57.2%, and 40.2% with an AUC of 0.804, indicating a good accuracy and reliability of the nomogram. GSEA showed that the high-risk group had lower ferroptosis and immune response. TME analyses confirmed that the high-risk group had lower immune cell infiltration (e.g., CD8+ T cells, CD4+ memory-activated T cells, and M1 macrophages) and lower immune functions (e.g., immune checkpoint activation). Low-risk patients whose disease expressed PD1 or CTLA4 were likely to respond better to ICIs. The analysis demonstrated that the TMB had significantly difference between low- and high- risk groups. Chemotherapy drugs, such as sorafenib, Imatinib, ABT.888 (Veliparib), Docetaxel, and Paclitaxel showed Significant differences in the estimated IC50 between the two risk groups. Overall, our novel ferroptosis-related lncRNA signature was able to accurately predict the prognosis and ICI outcomes of CM patients. These ferroptosis-related lncRNAs might be potential biomarkers and therapeutic targets for CM.

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Echocardiography and EuroSCORE II for the stratification of low-gradient severe aortic stenosis and preserved left ventricular ejection fraction

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-021-02373-2 ◽

2021 ◽

Author(s):

Yan Fan ◽

Hong Shen ◽

Brandon Stacey ◽

David Zhao ◽

Robert J. Applegate ◽

...

Keyword(s):

High Risk ◽

Left Ventricular Ejection Fraction ◽

Risk Group ◽

Severe Aortic Stenosis ◽

Left Ventricular ◽

High Risk Group ◽

Low Risk ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Risk Patients

AbstractThe purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.

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Short-term risk stratification using CADILLAC risk score in patients with ST elevation myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1352 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Satou ◽

H Kitahara ◽

K Ishikawa ◽

T Nakayama ◽

Y Fujimoto ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Adverse Events ◽

Risk Score ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Short Term ◽

Recurrent Myocardial Infarction ◽

St Elevation

Abstract Background The recent reperfusion therapy for ST-elevation myocardial infarction (STEMI) has made the length of hospital stay shorter without adverse events. CADILLAC risk score is reportedly one of the risk scores predicting the long-term prognosis in STEMI patients. Purpose To invenstigate the usefulness of CADILLAC risk score for predicting short-term outcomes in STEMI patients. Methods Consecutive patients admitted to our university hospital and our medical center with STEMI (excluding shock, arrest case) who underwent primary PCI between January 2012 and April 2018 (n=387) were enrolled in this study. The patients were classified into 3 groups according to the CADILLAC risk score: low risk (n=176), intermediate risk (n=87), and high risk (n=124). Data on adverse events within 30 days after hospitalization, including in-hospital death, sustained ventricular arrhythmia, recurrent myocardial infarction, heart failure requiring intravenous treatment, stroke, or clinical hemorrhage, were collected. Results In the low risk group, adverse events within 30 days were significantly less observed, compared to the intermediate and high risk groups (n=13, 7.4% vs. n=13, 14.9% vs. n=58, 46.8%, p<0.001). In particular, all adverse events occurred within 3 days in the low risk group, although adverse events, such as heart failure (n=4), recurrent myocardial infarction (n=1), stroke (n=1), and gastrointestinal bleeding (n=1), were substantially observed after day 4 of hospitalization in the intermediate and high risk groups. Conclusions In STEMI patients with low CADILLAC risk score, better short-term prognosis was observed compared to the intermediate and high risk groups, and all adverse events occurred within 3 days of hospitalization, suggesting that discharge at day 4 might be safe in this study population. CADILLAC risk score may help stratify patient risk for short-term prognosis and adjust management of STEMI patients. Initial event occurrence timing Funding Acknowledgement Type of funding source: None

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Pre-hospital risk assessment in suspected non-ST-elevation acute coronary syndrome: A prospective observational study

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872618813846 ◽

2018 ◽

Vol 9 (1_suppl) ◽

pp. 5-12 ◽

Cited By ~ 12

Author(s):

Dominique N van Dongen ◽

Rudolf T Tolsma ◽

Marion J Fokkert ◽

Erik A Badings ◽

Aize van der Sluis ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Risk Stratification ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Heart Score ◽

Coronary Syndrome ◽

Risk Patients ◽

St Elevation

Background: Pre-hospital risk stratification of non-ST-elevation acute coronary syndrome (NSTE-ACS) by the complete HEART score has not yet been assessed. We investigated whether pre-hospital risk stratification of patients with suspected NSTE-ACS using the HEART score is accurate in predicting major adverse cardiac events (MACE). Methods: This is a prospective observational study, including 700 patients with suspected NSTE-ACS. Risk stratification was performed by ambulance paramedics, using the HEART score; low risk was defined as HEART score ⩽ 3. Primary endpoint was occurrence of MACE within 45 days after inclusion. Secondary endpoint was myocardial infarction or death. Results: A total of 172 patients (24.6%) were stratified as low risk and 528 patients (75.4%) as intermediate to high risk. Mean age was 53.9 years in the low risk group and 66.7 years in the intermediate to high risk group ( p<0.001), 50% were male in the low risk group versus 60% in the intermediate to high risk group ( p=0.026). MACE occurred in five patients in the low risk group (2.9%) and in 111 (21.0%) patients at intermediate or high risk ( p<0.001). There were no deaths in the low risk group and the occurrence of acute myocardial infarction in this group was 1.2%. In the high risk group six patients died (1.1%) and 76 patients had myocardial infarction (14.4%). Conclusions: In suspected NSTE-ACS, pre-hospital risk stratification by ambulance paramedics, including troponin measurement, is accurate in differentiating between low and intermediate to high risk. Future studies should investigate whether transportation of low risk patients to a hospital can be avoided, and whether high risk patients benefit from immediate transfer to a hospital with early coronary angiography possibilities.

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Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer

10.21203/rs.3.rs-49217/v1 ◽

2020 ◽

Author(s):

Jianfeng Zheng ◽

Jinyi Tong ◽

Benben Cao ◽

Xia Zhang ◽

Zheng Niu

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Risk Score ◽

Immune Cell ◽

Risk Group ◽

Risk Groups ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Training Set ◽

Score Model

Abstract Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.

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