scholarly journals Identification of an independent immune-genes prognostic index for renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guangyao Li ◽  
Xiyi Wei ◽  
Shifeng Su ◽  
Shangqian Wang ◽  
Wei Wang ◽  
...  

Abstract Background Considerable evidence has indicated an association between the immune microenvironment and clinical outcome in ccRCC. The purpose of this study is to extensively figure out the influence of immune-related genes of tumors on the prognosis of patients with ccRCC. Methods Files containing 2498 immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort), and the transcriptome data and clinical information relevant to patients with ccRCC were identified and downloaded from the TCGA data-base. Univariate and multivariate Cox regression analyses were used to screen out prognostic immune genes. The immune risk score model was established in light of the regression coefficient between survival and hub immune-related genes. We eventually set up a nomogram for the prediction of the overall survival for ccRCC. Kaplan-Meier (K-M) and ROC curve was used in evaluating the value of the predictive risk model. A P value of < 0.05 indicated statistically significant differences throughout data analysis. Results Via differential analysis, we found that 556 immune-related genes were expressed differentially between tumor and normal tissues (p < 0. 05). The analysis of univariate Cox regression exhibited that there was a statistical correlation between 43 immune genes and survival risk in patients with ccRCC (p < 0.05). Through Lasso-Cox regression analysis, we established an immune genetic risk scoring model based on 18 immune-related genes. The high-risk group showed a bad prognosis in K-M analysis. (p < 0.001). ROC curve showed that it was reliable of the immune risk score model to predict survival risk (5 year over survival, AUC = 0.802). The model indicated satisfactory AUC and survival correlation in the validation data set (5 year OS, Area Under Curve = 0.705, p < 0.05). From Multivariate regression analysis, the immune-risk score model plays an isolated role in the prediction of the prognosis of ccRCC. Under multivariate-Cox regression analysis, we set up a nomogram for comprehensive prediction of ccRCC patients’ survival rate. At last, it was identified that 18 immune-related genes and risk scores were not only tremendously related to clinical prognosis but also contained in a variety of carcinogenic pathways. Conclusion In general, tumor immune-related genes play essential roles in ccRCC development and progression. Our research established an unequal 18-immune gene risk index to predict the prognosis of ccRCC visually. This index was found to be an independent predictive factor for ccRCC.

2020 ◽  
Author(s):  
Qi Zou ◽  
Yue Ding ◽  
Yuxiang Dong ◽  
Dejun Wu ◽  
Junyi Wang ◽  
...  

Abstract Background: RNA binding proteins (RBPs) are now under discussion as novel promising bio-markers for patients with colon cancer. The purpose of our study is to identify several RBPs related to the progression and prognosis of colon cancer, and to further investigate the mechanism of their influence on tumor progression. Methods: The transcriptome data of colon cancer as well as clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas (TCGA) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were performed to elucidate the gene functions and relative pathways. Cox and lasso regression analysis were used to analyze the effect of immune genes on the prognosis of breast cancer. Immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate cox regression analysis was utilized to investigate whether the immune genes risk score model was an independent factor for predicting the prognosis of breast cancer. Nomogram was constructed to comprehensively predict the survival rate of breast cancer. P< 0.05 was considered to be statistically significant. Results: The results of the difference analysis showed that 473 RBPs exhibited differential expression between normal and colon cancer tissues (p<0. 05). Univariate cox regression analysis revealed 25 RBPs statistically correlated with colon cancer related survival risk (P<0.05). In addition, a 10-RBPs based risk scoring model was constructed through multivariate cox regression analysis. KM curve indicated that patients in high-risk were associated with poor outcomes (p<0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year OS, AUC=0.782). Our model showed satisfying AUC and survival correlation in the validation dataset (5-year OS AUC=0.744). Furthermore, multivariate cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer. A nomogram was established to comprehensively predict the survival of colon cancer patients with the results of multivariate cox regression analysis. Finally, we found that 10 RBPs and risk scores were significantly associated with clinical factors and prognosis, and were involved in multiple oncogenic pathways. Conclusion: Collectively, RBPs played an essential role in the progression and prognosis of colon cancer by regulating multiple biological pathways. Furthermore, RBPs risk score was an independent predictive factor of colon cancer, indicating a poor survival.


2020 ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Chen Chen ◽  
Junyi Wang ◽  
...  

Abstract Objective Increasing evidence has indicated an association between immune micro-environment in breast cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of tumor immune genes on the prognosis of breast cancer patients. Methods 2498 immune genes were downloaded from ImmPort database. Additionally, we identified and downloaded the transcriptome data of patients with breast cancer from the TCGA database through the R package, as well as relevant clinical information. Survival R package was applied in survival analyses for hub-genes. Cox regression analysis was used to analyze the effect of immune genes on the prognosis of breast cancer. Immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate cox regression analysis was utilized to investigate whether the immune genes risk score model was an independent factor for predicting the prognosis of breast cancer. Nomogram was constructed to comprehensively predict the survival rate of breast cancer. P < 0.05 was considered to be statistically significant. Results The results of the difference analysis showed that 556 immune genes exhibited differential expression between normal and breast cancer tissues (p < 0. 05). Univariate cox regression analysis revealed 66 immune genes statistically correlated with breast cancer related survival risk, of which 30 were associated with overall survival (P < 0.05). In addition, a 15-genes based immune genes risk scoring model was constructed through lasso COX regression analysis. KM curve indicated that patients in high-risk were associated with poor outcomes (p < 0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year OS, AUC = 0.752). Our model showed satisfying AUC and survival correlation in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Furthermore, multivariate cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of breast cancer. A nomogram was established to comprehensively predict the survival of breast cancer patients with the results of multivariate cox regression analysis. Finally, we found that 15 immune genes and risk scores were significantly associated with clinical factors and prognosis, and were involved in multiple oncogenic pathways. Conclusion Collectively, tumor immune genes played an essential role in the prognosis of breast cancer. Furthermore, immune risk score was an independent predictive factor of breast cancer, indicating a poor survival.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhipeng Zhu ◽  
Mengyu Song ◽  
Wenhao Li ◽  
Mengying Li ◽  
Sihan Chen ◽  
...  

Hepatocellular carcinoma is a common malignant tumor with poor prognosis, poor treatment effect, and lack of effective biomarkers. In this study, bioinformatics analysis of immune-related genes of hepatocellular carcinoma was used to construct a multi-gene combined marker that can predict the prognosis of patients. The RNA expression data of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the IMMPORT database. Differential analysis was performed by Wilcox test to obtain differentially expressed genes. Univariate Cox regression analysis, lasso regression analysis and multivariate Cox regression analysis were performed to establish a prognostic model of immune genes, a total of 5 genes (HDAC1, BIRC5, SPP1, STC2, NR6A1) were identified to construct the models. The expression levels of 5 genes in HCC tissues were significantly different from those in paracancerous tissues. The Kaplan-Meier survival curve showed that the risk score calculated according to the prognostic model was significantly related to the overall survival (OS) of HCC. The receiver operating characteristic (ROC) curve confirmed that the prognostic model had high accuracy. Independent prognostic analysis was performed to prove that the risk value can be used as an independent prognostic factor. Then, the gene expression data of hepatocellular carcinoma in the ICGC database was used as a validation data set for the verification of the above steps. In addition, we used the CIBERSORT software and TIMER database to conduct immune infiltration research, and the results showed that the five genes of the model and the risk score have a certain correlation with the content of immune cells. Moreover, through Gene Set Enrichment Analysis (GSEA) and the construction of protein interaction networks, we found that the p53-mediated signal transduction pathway is a potentially important signal pathway for hepatocellular carcinoma and is positively regulated by certain genes in the prognostic model. In conclusion, this study provides potential targets for predicting the prognosis and treatment of hepatocellular carcinoma patients, and also provides new ideas about the correlation between immune genes and potential pathways of hepatocellular carcinoma.


2020 ◽  
Author(s):  
Chao Qin ◽  
Guangyao Li ◽  
Xiyi Wei ◽  
Shifeng Su ◽  
Shangqian Wang ◽  
...  

Abstract Objective: Increasing evidence has indicated an association between immune micro-environment in clear cell renal cell carcinoma (ccRCC) and clinical outcomes. The aim of this research is to comprehensively investigate the effect of tumor immune genes on the prognosis of ccRCC patients. Methods: 2498 immune genes were downloaded from ImmPort database. Additionally, we identified and downloaded the transcriptome data of patients with ccRCC from the TCGA database through the R package, as well as relevant clinical information. We apply certain survival R package to analyse the survival of hub-genes before analyzing the effect of immune genes on the prognosis of clear cell renal cell carcinoma (ccRCC) utilizing Cox regression analysis. Based on the statistical correlation between hub immune gene and survival ,immune risk score model was set up.We finally constructed a nomogram to predict the survival rate of ccRCC overally. In addition, whether the immune gene risk score model is an independent prognostic factor for ccRCC is comprehensively considered applying multivariate cox regression analysis. It is worth noting that throughout the data analysis, P< 0.05 was recognized to be of significance statistically. Results: The results of the difference analysis showed that 556 immune genes exhibited differential expression between normal and ccRCC tissues (p<0. 05). Univariate cox regression analysis revealed 43 immune genes statistically correlated with ccRCC related survival risk (P<0.05). In addition, a 18-genes based immune genes risk scoring model was constructed through lasso COX regression analysis. KM curve indicated that patients in high-risk were associated with poor outcomes (p<0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year OS, AUC=0.802). Our model showed satisfying AUC and survival correlation in the validation dataset ( 5-year OS AUC=0.705, P<0.001). Furthermore, multivariate cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of ccRCC. A nomogram was established to comprehensively predict the survival of ccRCC patients with the results of multivariate cox regression analysis. Finally, we found that 15 immune genes and risk scores were significantly associated with clinical factors and prognosis, and were involved in multiple oncogenic pathways.Conclusion: Collectively, tumor immune genes played an essential role in the prognosis of ccRCC. Furthermore, immune risk score was an independent predictive factor of ccRCC, indicating a poor survival.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.


2021 ◽  
Vol 16 ◽  
Author(s):  
Dongqing Su ◽  
Qianzi Lu ◽  
Yi Pan ◽  
Yao Yu ◽  
Shiyuan Wang ◽  
...  

Background: Breast cancer has plagued women for many years and caused many deaths around the world. Method: In this study, based on the weighted correlation network analysis, univariate Cox regression analysis and least absolute shrinkage and selection operator, 12 immune-related genes were selected to construct the risk score for breast cancer patients. The multivariable Cox regression analysis, gene set enrichment analysis and nomogram were also conducted in this study. Results: Good results were obtained in the survival analysis, enrichment analysis, multivariable Cox regression analysis and immune-related feature analysis. When the risk score model was applied in 22 breast cancer cohorts, the univariate Cox regression analysis demonstrated that the risk score model was significantly associated with overall survival in most of the breast cancer cohorts. Conclusion: Based on these results, we could conclude that the proposed risk score model may be a promising method, and may improve the treatment stratification of breast cancer patients in the future work.


2020 ◽  
Vol 2020 ◽  
pp. 1-43
Author(s):  
Beilei Wu ◽  
Lijun Tao ◽  
Daqing Yang ◽  
Wei Li ◽  
Hongbo Xu ◽  
...  

Objective. Stromal cells and immune cells have important clinical significance in the microenvironment of colorectal cancer (CRC). This study is aimed at developing a CRC gene signature on the basis of stromal and immune scores. Methods. A cohort of CRC patients (n=433) were adopted from The Cancer Genome Atlas (TCGA) database. Stromal/immune scores were calculated by the ESTIMATE algorithm. Correlation between prognosis/clinical characteristics and stromal/immune scores was assessed. Differentially expressed stromal and immune genes were identified. Their potential functions were annotated by functional enrichment analysis. Cox regression analysis was used to develop an eight-gene risk score model. Its predictive efficacies for 3 years, 5 years, overall survival (OS), and progression-free survival interval (PFI) were evaluated using time-dependent receiver operating characteristic (ROC) curves. The correlation between the risk score and the infiltering levels of six immune cells was analyzed using TIMER. The risk score was validated using an independent dataset. Results. Immune score was in a significant association with prognosis and clinical characteristics of CRC. 736 upregulated and two downregulated stromal and immune genes were identified, which were mainly enriched into immune-related biological processes and pathways. An-eight gene prognostic risk score model was conducted, consisting of CCL22, CD36, CPA3, CPT1C, KCNE4, NFATC1, RASGRP2, and SLC2A3. High risk score indicated a poor prognosis of patients. The area under the ROC curves (AUC) s of the model for 3 years, 5 years, OS, and PFI were 0.71, 0.70, 0.73, and 0.66, respectively. Thus, the model possessed well performance for prediction of patients’ prognosis, which was confirmed by an external dataset. Moreover, the risk score was significantly correlated with immune cell infiltration. Conclusion. Our study conducted an immune-related prognostic risk score model, which could provide novel targets for immunotherapy of CRC.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiaoqing Yu ◽  
Jingsong Zhang ◽  
Rui Yang ◽  
Chun Li

Objective. Many studies have found that long noncoding RNAs (lncRNAs) are differentially expressed in hepatocellular carcinoma (HCC) and closely associated with the occurrence and prognosis of HCC. Since patients with HCC are usually diagnosed in late stages, more effective biomarkers for early diagnosis and prognostic prediction are in urgent need. Methods. The RNA-seq data of liver hepatocellular carcinoma (LIHC) were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs and mRNAs were obtained using the edgeR package. The single-sample networks of the 371 tumor samples were constructed to identify the candidate lncRNA biomarkers. Univariate Cox regression analysis was performed to further select the potential lncRNA biomarkers. By multivariate Cox regression analysis, a 3-lncRNA-based risk score model was established on the training set. Then, the survival prediction ability of the 3-lncRNA-based risk score model was evaluated on the testing set and the entire set. Function enrichment analyses were performed using Metascape. Results. Three lncRNAs (RP11-150O12.3, RP11-187E13.1, and RP13-143G15.4) were identified as the potential lncRNA biomarkers for LIHC. The 3-lncRNA-based risk model had a good survival prediction ability for the patients with LIHC. Multivariate Cox regression analysis proved that the 3-lncRNA-based risk score was an independent predictor for the survival prediction of patients with LIHC. Function enrichment analysis indicated that the three lncRNAs may be associated with LIHC via their involvement in many known cancer-associated biological functions. Conclusion. This study could provide novel insights to identify lncRNA biomarkers for LIHC at a molecular network level.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jiannan Yao ◽  
Ling Duan ◽  
Xuying Huang ◽  
Jian Liu ◽  
Xiaona Fan ◽  
...  

BackgroundEsophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer and the seventh most prevalent cause of cancer-related death worldwide. Tumor microenvironment (TME) has been confirmed to play an crucial role in ESCC progression, prognosis, and the response to immunotherapy. There is a need for predictive biomarkers of TME-related processes to better prognosticate ESCC outcomes.AimTo identify a novel gene signature linked with the TME to predict the prognosis of ESCC.MethodsWe calculated the immune/stromal scores of 95 ESCC samples from The Cancer Genome Atlas (TCGA) using the ESTIMATE algorithm, and identified differentially expressed genes (DEGs) between high and low immune/stromal score patients. The key prognostic genes were further analyzed by the intersection of protein–protein interaction (PPI) networks and univariate Cox regression analysis. Finally, a risk score model was constructed using multivariate Cox regression analysis. We evaluated the associations between the risk score model and immune infiltration via the CIBERSORT algorithm. Moreover, we validated the signature using the Gene Expression Omnibus (GEO) database. Within the ten gene signature, five rarely reported genes were further validated with quantitative real time polymerase chain reaction (qRT-PCR) using an ESCC tissue cDNA microarray.ResultsA total of 133 up-regulated genes were identified as DEGs. Ten prognostic genes were selected based on intersection analysis of univariate COX regression analysis and PPI, and consisted of C1QA, C1QB, C1QC, CD86, C3AR1, CSF1R, ITGB2, LCP2, SPI1, and TYROBP (HR&gt;1, p&lt;0.05). The expression of 9 of these genes in the tumor samples were significantly higher compared to matched adjacent normal tissue based on the GEO database (p&lt;0.05). Next, we assessed the ability of the ten-gene signature to predict the overall survival of ESCC patients, and found that the high-risk group had significantly poorer outcomes compared to the low-risk group using univariate and multivariate analyses in the TCGA and GEO cohorts (HR=2.104, 95% confidence interval:1.343-3.295, p=0.001; HR=1.6915, 95% confidence interval:1.053-2.717, p=0.0297). Additionally, receiver operating characteristic (ROC) curve analysis demonstrated a relatively sensitive and specific profile for the signature (1-, 2-, 3-year AUC=0.672, 0.854, 0.81). To identify the basis for these differences in the TME, we performed correlation analyses and found a significant positive correlation with M1 and M2 macrophages and CD8+ T cells, as well as a strong correlation to M2 macrophage surface markers. A nomogram based on the risk score and select clinicopathologic characteristics was constructed to predict overall survival of ESCC patients. For validation, qRT-PCR of an ESCC patient cDNA microarray was performed, and demonstrated that C1QA, C3AR1, LCP2, SPI1, and TYROBP were up-regulated in tumor samples and predict poor prognosis.ConclusionThis study established and validated a novel 10-gene signature linked with M2 macrophages and poor prognosis in ESCC patients. Importantly, we identified C1QA, C3AR1, LCP2, SPI1, and TYROBP as novel M2 macrophage-correlated survival biomarkers. These findings may identify potential targets for therapy in ESCC patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12554
Author(s):  
Liming Zheng ◽  
Xi Gu ◽  
Guojun Zheng ◽  
Xin Li ◽  
Meifang He ◽  
...  

Background Early recurrence of hepatocellular carcinoma (HCC) is a major obstacle to improving the prognosis, and no widely accepted adjuvant therapy guideline for patients post-liver resection is available. Currently, all available methods and biomarkers are insufficient to accurately predict post-operation HCC patients’ risk of early recurrence and their response to adjuvant therapy. Methods In this study, we downloaded four gene expression datasets (GSE14520, GSE54236, GSE87630, and GSE109211) from the Gene Expression Omnibus database and identified 34 common differentially expressed genes associated with HCC dysregulation and response to adjuvant sorafenib. Then, we constructed a novel 11-messenger RNA predictive model by using ROC curves analysis, univariate Cox regression analysis, and LASSO Cox regression analysis. Furthermore, we validated the predictive values of the risk model in GSE14520 and TCGA-LIHC cohorts by using Kaplan–Meier survival analysis, multivariable Cox regression analysis, and decision curve analysis, respectively. Results The risk score model could identify patients with a high risk of HCC recurrence at the early stage and could predict the response of patients to adjuvant sorafenib. Patients with a high risk score had a worse recurrence rate in training cohorts (2-year: p < 0.0001, hazard ratio (HR): 4.658, confidence interval 95% CI [2.895–7.495]; 5-year: p < 0.0001, HR: 3.251, 95% CI [2.155–4.904]) and external validation cohorts (2-year: p < 0.001, HR: 3.65, 95% CI [2.001–6.658]; 5-year: p < 0.001, HR: 3.156, 95% CI [1.78–5.596]). The AUC values of the risk score model for predicting tumor early recurrence were 0.746 and 0.618, and that of the risk score model for predicting the response to adjuvant sorafenib were 0.722 and 0.708 in the different cohort, respectively. Multivariable Cox regression analysis and decision curve analysis also showed that the risk score model was superior to and independent of other clinicopathologic characteristics. Moreover, the risk score model had excellent abilities to predict the overall survival and HCC recurrence of patients with the same tumor stage category. Conclusions Our risk model is a reliable and superior predictive tool. With this model, we could optimize the risk stratification based on early tumor recurrence and could evaluate the response of patients to adjuvant sorafenib after liver resection.


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