DNA Repair and Replication-Related Gene Signature Based on Tumor Mutation Burden Reveals Prognostic and Immunotherapy Response in Gastric Cancer

The genomic variant features (mutations, deletions, structural variants, etc.) within gastric cancer impact its evolution and immunogenicity. The tumor has developed several coping strategies to respond to these changes by DNA repair and replication (DRR). However, the intrinsic relationship between the associated DRR-related genes and gastric cancer progression remained unknown. This study selected DRR-related genes with tumor mutation burden based on the TCGA (The Cancer Genome Atlas) database of gastric cancer transcriptome and mutation data. The prognosis model of seven genes (LAMA2, CREB3L3, SELP, ABCC9, CYP1B1, CDH2, and GAMT) was constructed by a univariate and LASSO regression analysis and divided into high-risk and low-risk groups with the median risk score. Survival analysis showed that overall survival (OS) was lower in the high-risk group than that in the low-risk group. Moreover, patients with gastric cancer in the high-risk group have worse survival in different subgroups, including age, gender, histological grade, and TNM stage. The nomogram that included risk scores for DRR-related genes could accurately foresee OS of patients with gastric cancer. Interestingly, the tumor mutation burden score was higher in the low-risk group than that in the high-risk group, and the risk score for DRR-related genes was negatively correlated with tumor mutation burden in gastric cancer. Next, we further combined the risk score and tumor mutation burden to evaluate the prognosis of gastric cancer patients. The low-risk cohort had a better prognosis than the high-risk cohort in the high tumor mutation burden subgroup. The number of mutation types in the high-risk group was lower than that in the low-risk group. In the immune microenvironment of gastric cancer, more naïve B cells, memory resting CD4+ T cells, Treg cells, monocytes cells, and resting mast cells were infiltrated in the high-risk group. At last, PD-L1 and IAP expressions were negatively correlated with the risk scores; patients with gastric cancer in the low-risk group showed better immunotherapy outcomes than those in the high-risk group. Overall, the DRR-related gene signature based on tumor mutation burden is a novel biomarker for prognostic and immunotherapy response in patients with gastric cancer.

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A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Therapeutic Response of Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.736682 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shilang Xiao ◽

Xiaoming Liu ◽

Lingzhi Yuan ◽

Fen Wang

Keyword(s):

Gastric Cancer ◽

High Risk ◽

Correlation Analysis ◽

Risk Score ◽

Therapeutic Response ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Biological Processes ◽

Spearman Correlation

Background: Accumulating literature demonstrates that long noncoding RNAs (lncRNAs) are involved in ferroptosis and gastric cancer progression. However, the predictive value of ferroptosis-related lncRNAs for prognosis and therapeutic response is yet to be elucidated in gastric cancer (GC).Method: The transcriptomic data and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The association between ferroptosis-related lncRNAs and ferroptosis regulators was analyzed by Spearman correlation analysis. Then, we established a risk predictive model based on the ferroptosis-related lncRNAs using multivariate Cox regression analysis. Furthermore, we performed correlation analysis for the risk score and characteristics of biological processes, immune landscape, stromal activity, genomic integrity, drug response, and immunotherapy efficacy.Results: We constructed a 17-ferroptosis-related-lncRNA signature via multivariate Cox analysis to divide patients into two groups: low- and high-risk groups. The low-risk group was linked to prolonged overall survival and relapse-free survival. The risk score had good predictive ability to predict the prognosis of GC patients compared with other clinical biomarkers. We found that the high-risk group was associated with activation of carcinogenetic signaling pathways, including stromal activation, epithelial-mesenchymal-transition (EMT) activation, and immune escape through integrated bioinformatics analysis. In contrast, the low-risk group was associated with DNA replication, immune-flamed state, and genomic instability. Additionally, through Spearman correlation analysis, we found that patients in the high-risk group may respond well to drugs targeting cytoskeleton, WNT signaling, and PI3K/mTOR signaling, and drugs targeting chromatin histone acetylation, cell cycle, and apoptosis regulation could bring more benefits for the low-risk group. The high-risk group was associated with poor immunotherapy efficacy.Conclusion: Our study systematically evaluated the role of ferroptosis-related lncRNAs in t tumor microenvironment, therapeutic response, and prognosis of GC. Risk score–based stratification could reflect the characteristic of biological processes, immune landscape, stromal activity, genomic stability, and pharmaceutical profile in GC patients. The ferroptosis-related lncRNA signature could serve as a reliable biomarker to predict prognosis and therapeutic response of patients with GC.

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A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma

Scientific Reports ◽

10.1038/s41598-021-97102-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yang Peng ◽

Haochen Yu ◽

Yingzi Zhang ◽

Fanli Qu ◽

Zhenrong Tang ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Breast Carcinoma ◽

Risk Score ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Luminal Type

AbstractFerroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients. We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of the immune microenvironment and the probability of a response to immunotherapy and chemotherapy. The patients were divided into a high-risk group and a low-risk group according to the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14–1.76, P = 0.002; HR, 2.19, 95% CI, 1.13–4.26, P = 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, the low-risk group was much more sensitive to immunotherapy, and six drugs might have potential therapeutic implications in the high-risk group. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed favorable discriminative ability and could help guide clinical decision-making for luminal-type breast carcinoma.

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Molecular Analysis of Prognosis and Immune Pathways of Pancreatic Cancer Based on TNF Family Members

Journal of Oncology ◽

10.1155/2021/2676996 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Zemin Zhu ◽

Caixi Tang ◽

Tao Xu ◽

Zhijian Zhao

Keyword(s):

High Risk ◽

Risk Score ◽

Risk Group ◽

Family Members ◽

Enrichment Analysis ◽

High Risk Group ◽

Low Risk ◽

Risk Scores ◽

Score Model ◽

Vesicle Cycle

Background. Tumor necrosis factor (TNF) family members play a vital role in anticancer therapy. This study aimed to screen the critical markers for the prognostic analysis of pancreatic adenocarcinoma (PAAD) by analyzing the clustering patterns of TNF family members in PAAD. Methods. In this study, the NMF clustering method was adopted to cluster samples from The Cancer Genome Atlas (TCGA) to acquire the clustering pattern of the TNF family in PAAD. Differential gene analysis was performed according to TNF family gene clusters. The support vector machine (SVM) method was conducted for further gene screening, and the risk score model of the screened genes was constructed by Lasso. The single sample gene set enrichment analysis (ssGSEA) method was adopted for immunoenrichment analysis and tumor immune cycle analysis. Genes associated with risk scores were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results. We clustered PAAD into two groups based on TNF family genes. Nineteen TNF family genes were significantly associated with the clinical characteristics of PAAD patients. The risk score formula was composed of RHOD, UBE2C, KLHDC7b, MSLN, ADAM8, NME3, GNG2, and MCOLN3. GSE57495 and GSE62452 datasets verified that patients in the high-risk group had a worse prognosis than those in the low-risk group. The risk score-related genes analyzed by GO and KEGG were mainly involved in the modulation of chemical synaptic transmission and synaptic vesicle cycle pathway. There were significant differences in the expression of 15 immune cells between the high-risk group and the low-risk group. The risk score was positively correlated with HCK, interferon, MHC-I, and STAT1. The expression of genes relevant to chemokine, immunostimulator, MHC, and receptor was strongly associated with the risk score. Conclusion. The risk score model based on the TNF family can predict the prognosis and immune status of PAAD patients. Further research is needed to verify the clinical prognostic value of risk scores.

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Identification of Metastasis-Related Signature For Predicting Survival In Osteosarcoma

10.21203/rs.3.rs-683582/v1 ◽

2021 ◽

Author(s):

Song Shi ◽

Shuaijie Yang ◽

Zhenyu Zhou ◽

Kai Sun ◽

Ran Tao ◽

...

Keyword(s):

High Risk ◽

Risk Score ◽

Immune Cell ◽

Cox Regression ◽

Risk Group ◽

Expression Profiles ◽

Gene Signature ◽

Low Risk ◽

Risk Scores ◽

Activation Markers

Abstract BackgroundRNA sequencing has become a powerful tool for exploring tumor recurrence or metastasis mechanisms. In this study, we aimed to develop a signature to improve the prognostic predictions of osteosarcoma.Materials and methodsBy comparing the expression profiles between metastatic and non-metastatic samples, we obtained 57 metastatic-related gene signatures. Then we constructed a 3‐gene signature to predict the prognostic risk of osteosarcoma patients by the Cox proportional hazards regression model. The risk score derived from this signature could successfully stratify osteosarcoma patients into subgroups with different survival outcomes.ResultsPatients in the low-risk group showed more prolonged overall survival than those in the high-risk group. And the performance was validated with another independent dataset. Multivariate cox regression revealed that the risk score served as an independent risk factor. Besides, we found that patients with low-risk scores had higher expression levels of immune-related signatures, suggesting an active immune status in those patients. Using the CIBERSORT database, we further systematically analyzed the relationships between the risk score and immune cell infiltration levels, as well as the immune activation markers. Higher infiltration of immune cells (CD8 T cells, monocytes, M2 macrophages, and memory B cells) and higher levels of immune cytotoxic markers (GZMA, GMZB, IFNG, and TNF) were observed in patients in the low-risk group.ConclusionsIn summary, this 3-gene signature could be a reliable marker for prognostic evaluation and help clinicians identify high‐risk patients.

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A ferroptosis-associated gene signature for the prediction of prognosis and therapeutic response in luminal-type breast carcinoma

10.21203/rs.3.rs-125141/v2 ◽

2021 ◽

Author(s):

Yang Peng ◽

Haochen Yu ◽

Yingzi Zhang ◽

Fanli Qu ◽

Zhenrong Tang ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Breast Carcinoma ◽

Risk Score ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Luminal Type

Abstract Background: Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients.Methods: We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of mutations, copy number variations (CNVs), the immune microenvironment and the probability of a response to immunotherapy and chemotherapy.Findings: The patients were divided into a high-risk group and a low-risk group by the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14-1.76, P = 0.002; HR, 2.19, 95% CI, 1.13-4.26, P= 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high-risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, and the low-risk group was much more sensitive to immunotherapy and six drugs might have potential therapeutic implications in high- risk group. In addition, we found that amplifications on chromosome 11 accompanied by the deletion of chromosome 1 were enriched in the high-risk subgroup. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed a favorable discriminating ability and might contribute to clinical decision-making for luminal-type breast carcinoma.

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A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer

Cell Death Discovery ◽

10.1038/s41420-021-00451-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ying Ye ◽

Qinjin Dai ◽

Hongbo Qi

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Low Risk ◽

Differentially Expressed ◽

Related Gene

AbstractOvarian cancer (OC) is a highly malignant gynaecological tumour that has a very poor prognosis. Pyroptosis has been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes in OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators that were differentially expressed between OC and normal ovarian tissues. Based on these differentially expressed genes (DEGs), all OC cases could be divided into two subtypes. The prognostic value of each pyroptosis-related gene for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 7-gene signature was built and classified all OC patients in the TCGA cohort into a low- or high-risk group. OC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, OC patients from a Gene Expression Omnibus (GEO) cohort were divided into two risk subgroups, and the low-risk group had increased overall survival (OS) time (P = 0.014). Combined with the clinical characteristics, the risk score was found to be an independent factor for predicting the OS of OC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched and that the immune status was decreased in the high-risk group. In conclusion, pyroptosis-related genes play important roles in tumour immunity and can be used to predict the prognosis of OCs.

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A Ferroptosis-associated Gene Signature for the Prediction of Prognosis and Therapeutic Response in Luminal-type Breast Carcinoma

10.21203/rs.3.rs-125141/v1 ◽

2020 ◽

Author(s):

Yang Peng ◽

Haochen Yu ◽

Yingzi Zhang ◽

Zhenrong Tang ◽

Chi Qu ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Breast Carcinoma ◽

Risk Score ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Low Risk ◽

Related Gene ◽

Luminal Type

Abstract Background: Ferroptosis is a new form of regulated cell death (RCD), and its emergence has provided a new approach to the progression and drug resistance of breast cancer (BRCA). However, there is still a great gap in the study of ferroptosis-related genes in BRCA, especially luminal-type BRCA patients.Methods: We downloaded the mRNA expression profiles and corresponding clinical data of BRCA patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) databases. Then, we built a prognostic multigene signature with ferroptosis-related differentially expressed genes (DEGs) in the METABRIC cohort and validated it in the TCGA cohort. The predictive value of this signature was investigated in terms of mutations, copy number variations (CNVs), the immune microenvironment, tumor purity, related pathway and the probability of a response to immunotherapy and chemotherapy.Findings: The patients were divided into a high-risk group and a low-risk group by the ferroptosis-associated gene signature, and the high-risk group had a worse overall survival (OS). The risk score based on the 10 ferroptosis-related gene-based signature was determined to be an independent prognostic predictor in both the METABRIC and TCGA cohorts (HR, 1.41, 95% CI, 1.14-1.76, P = 0.002; HR, 2.19, 95% CI, 1.13-4.26, P= 0.02). Gene set enrichment analysis indicated that the term “cytokine-cytokine receptor interaction” was enriched in the high risk score subgroup. Moreover, the immune infiltration scores of most immune cells were significantly different between the two groups, and the low-risk group was much more sensitive to immunotherapy and chemotherapy. In addition, we found that amplifications on chromosome 12 accompanied by the deletion of chromosome 21 were enriched in the high-risk subgroup. Pathway score results suggest that the ferroptosis-related gene-based signature show differences in most breast cancer-associated phenotypes. Finally, a nomogram incorporating a classifier based on the 10 ferroptosis-related genes, tumor stage, age and histologic grade was established. This nomogram showed a favorable discriminating ability and might contribute to clinical decision-making for luminal-type breast carcinoma.

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Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

10.21203/rs.3.rs-219997/v1 ◽

2021 ◽

Author(s):

Zhenyu Zhao ◽

Boxue He ◽

Qidong Cai ◽

Pengfei Zhang ◽

Xiong Peng ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Clinical Application ◽

Risk Group ◽

High Risk Group ◽

Immune Microenvironment ◽

Tumor Mutation Burden ◽

Immune Signature ◽

Immune Infiltration ◽

Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

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A Novel Ferroptosis-Related Gene Signature Robustly Predicts Clinical Prognosis And Tumor Immunity in Patients With Kidney Renal Clear Cell Carcinoma

10.21203/rs.3.rs-390254/v1 ◽

2021 ◽

Author(s):

Wei Song ◽

Weiting Kang ◽

Qi Zhang

Keyword(s):

High Risk ◽

Clear Cell ◽

Risk Group ◽

Gene Signature ◽

Renal Clear Cell Carcinoma ◽

High Risk Group ◽

Risk Scores ◽

Related Gene ◽

Clinical Prognosis ◽

Validation Set

Abstract Objective: This study aimed to construct a ferroptosis-related gene signature to predict clinical prognosis and tumor immunity in patients with kidney renal clear cell carcinoma (KIRC).Methods: The mRNA expression profiles and corresponding clinical data of KIRC patients were downloaded from The Cancer Genome Atlas (TCGA), which were randomly divided into training (398 patients) and validation set (132 patients). The iron death related (IDR) prediction model was constructed based on training set and 60 ferroptosis-related genes from previous literatures, followed by prognostic performance evaluation and verification using the validation set. Moreover, functional enrichment, immune cell infiltration, metagene clusters correlation, and TIDE scoring analyses were performed. Results: In total, 23 ferroptosis-related genes were significantly associated with overall survival (OS). The IDR prediction model (a 10-gene signature) was then constructed to stratify patients into two risk groups. The OS of KIRC patients with high-risk scores was significantly shorter than those with low-risk scores. Moreover, the risk score was confirmed as an independent prognostic predictor for OS. The positive and negative correlated genes with this model were significantly enriched in p53 signaling pathway, and cGMP-PKG signaling pathway. The patients in the high-risk group had higher ratios of plasma cells, T cells CD8, and T cells regulatory Tregs. Furthermore, IgG, HCK, LCK, and Interferson metagenes were significantly correlated with risk score. By TIDE score analysis, patients in the high-risk group could benefit from immunotherapy.Conclusions: The identified ferroptosis-related gene signature is significantly correlated with clinical prognosis and immune immunity in KIRC patients.

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A Four-gene Autophagy-related Prognostic Signature and Its Association With Immune Landscape in Lung Squamous Cell Carcinoma

10.21203/rs.3.rs-125355/v1 ◽

2020 ◽

Author(s):

Lumeng Luo ◽

Minghe Lv ◽

Xuan Li ◽

Tiankui Qiao ◽

Kuaile Zhao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Immune Suppression ◽

Risk Group ◽

Lung Squamous Cell Carcinoma ◽

High Risk Group ◽

Low Risk

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.

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