scholarly journals A Novel Signature of 23 Immunity-related Gene Pairs is Prognostic of Cutaneous Melanoma

Author(s):  
Yanan Xue ◽  
Yinan Xue ◽  
Zhengcai Wang ◽  
Yongzhen Mo ◽  
Pinyan Wang ◽  
...  

Abstract Background: We aimed to identify immune-related signature for predicting cutaneous melanoma (CM) prognosis. Methods: We used TCGA samples (n=471) to develop the best 23 Immune related gene pairs (23-IRGP) prognostic signature and divided patients into high- and low-immune risk group in TCGA dataset and validation datasets: GSE65904 (n=214), GSE59455 (n=141), and GSE22153 (n=79). Results: 23-IRGP presented precise ability in cutaneous melanoma (CM) which high-risk groups showed poor prognosis and indicated significant predict power in immune micro-environment and biological analysis as well. Conclusions: we established a novel promising prognostic model in CM and built the bridge between immune micro-environment and CM patient results. This approach can be applied to discover the signatures in other diseases without technical bias from different platforms.

2020 ◽  
Author(s):  
Jihang Luo ◽  
Puyu Liu ◽  
Leibo Wang ◽  
Yi Huang ◽  
Yuanyan Wang ◽  
...  

Abstract Background Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma(COAD) is the main pathological type of colon cancer. There is a lot of evidence describing the correlation between the prognosis of COAD and the immune system. The objective of the current study was the development of a robust prognostic immune-related gene pairs (IRGPs) model for estimating overall survival of COAD. Methods The gene expression profiles and clinical information of patients with colon adenocarcinoma come from TCGA and GEO databases and are divided into training and validation cohorts. Immune genes were selected which show significantly association with prognosis. Results Among 1647 immune genes, a 17 IRGPs model was built which was significantly associated with OS in the training cohort. In the training and validation data set, the IRGPs model divided patients into high-risk groups and low-risk groups, and the prognosis of the high-risk group was significantly worse( P <0.001). Univariate and multivariate Cox proportional hazard analysis confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways in high-risk groups were up-regulated. T cells regulatory and Macrophage M0 were significantly highly expressed in the high-risk group. Conclusion We successfully constructed an IRGPs model that can predict the prognosis of COAD, which provides new insights into the treatment strategy of COAD.


Author(s):  
Xianghong Zhou ◽  
Shi Qiu ◽  
Di Jin ◽  
Kun Jin ◽  
Xiaonan Zheng ◽  
...  

Abstract Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p<0.001). Combined with multiple clinical pathological factors, the results of multivariate analyses confirmed that this signature was an independent predictor of OS (HR, 3.548; 95%CI, 2.096−6.006; p<0.001). The results of immune infiltration analysis demonstrated that the abundance of multiple tumor-infiltration lymphocytes such as CD8+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.


2020 ◽  
Author(s):  
Jihang Luo ◽  
Puyu Liu ◽  
Leibo Wang ◽  
Yi Huang ◽  
Yuanyan Wang ◽  
...  

Abstract Background. Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma(COAD) is the main pathological type of colon cancer. There is a lot of evidence describing the correlation between the prognosis of COAD and the immune system. The objective of the current study was the development of a robust prognostic immune-related gene pairs (IRGPs) model for estimating overall survival of COAD. Methods. The gene expression profiles and clinical information of patients with colon adenocarcinoma come from TCGA and GEO databases and are divided into training and validation cohorts. Immune genes were selected which show significantly association with prognosis. Results. Among 1647 immune genes, a 17 IRGPs model was built which was significantly associated with OS in the training cohort. In the training and validation data set, the IRGPs model divided patients into high-risk groups and low-risk groups, and the prognosis of the high-risk group was significantly worse(P<0.001). Univariate and multivariate Cox proportional hazard analysis confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways in high-risk groups were up-regulated. T cells regulatory and Macrophage M0 were significantly highly expressed in the high-risk group. Conclusion. We successfully constructed an IRGPs model that can predict the prognosis of COAD, which provides new insights into the treatment strategy of COAD.


2021 ◽  
Vol 25 (6) ◽  
pp. 2918-2930
Author(s):  
Bao Zhang ◽  
Xiaocui Nie ◽  
Xinxin Miao ◽  
Shuo Wang ◽  
Jing Li ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qianshi Zhang ◽  
Zhen Feng ◽  
Yongnian Zhang ◽  
Shasha Shi ◽  
Yu Zhang ◽  
...  

Background. Colon cancer (CC) is a malignant tumor with a high incidence and poor prognosis. Accumulating evidence shows that the immune signature plays an important role in the tumorigenesis, progression, and prognosis of CC. Our study is aimed at establishing a novel robust immune-related gene pair signature for predicting the prognosis of CC. Methods. Gene expression profiles and corresponding clinical information are obtained from two public data sets: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, GSE39582). We screened out immune-related gene pairs (IRGPs) associated with prognosis in the discovery cohort. Lasso-Cox proportional hazard regression was used to develop the best prognostic signature model. According to this, the patients in the validation cohort were divided into high immune-risk group and low immune-risk group, and the prediction ability of the signature model was verified by survival analysis and independent prognostic analysis. Results. A total of 17 IRGPs composed of 26 IRGs were used to construct a prognostic-related risk scoring model. This model accurately predicted the prognosis of CC patients, and the patients in the high immune-risk group indicated poor prognosis in the discovery cohort and validation cohort. Besides, whether in univariate or multivariate analysis, the IRGP signature was an independent prognostic factor. T cell CD4 memory resting in the low-risk group was significantly higher than that in the high-risk group. Functional analysis showed that the biological processes of the low-risk group included “TCA cycle” and “RNA degradation,” while the high-risk group was enriched in the “CAMs” and “focal adhesion” pathways. Conclusion. We have successfully established a signature model composed of 17 IRGPs, which provides a novel idea to predict the prognosis of CC patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Na Li ◽  
Jiahong Wang ◽  
Xianquan Zhan

Accumulating evidence indicates that immunotherapy helped to improve the survival and quality-of-life of patients with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) besides chemotherapy and gene targeting treatment. This study aimed to develop immune-related gene signatures in LUAD and LUSC subtypes, respectively. LUAD and LUSC samples were divided into high- and low-abundance groups of immune cell infiltration (Immunity_H and Immunity_L) based on the abundance of immune cell infiltrations. The distribution of immune cells was significantly different between the high- and low-immunity subtypes in LUAD and LUSC samples. The differentially expressed genes (DEGs) between those two groups in LUAD and LUSC contain some key immune-related genes, such as PDL1, PD1, CTLA-4, and HLA families. The DEGs were enriched in multiple immune-related pathways. Furthermore, the seven-immune-related-gene-signature (CD1B, CHRNA6, CLEC12B, CLEC17A, CLNK, INHA, and SLC14A2) prognostic model-based high- and low-risk groups were significantly associated with LUAD overall survival and clinical characteristics. The eight-immune-related-gene-signature (C4BPB, FCAMR, GRAPL, MAP1LC3C, MGC2889, TRIM55, UGT1A1, and VIPR2) prognostic model-based high- and low-risk groups were significantly associated with LUSC overall survival and clinical characteristics. The prognostic models were tested as good ones by receiver operating characteristic, principal component analysis, univariate and multivariate analysis, and nomogram. The verifications of these two immune-related-gene-signature prognostic models showed consistency in the train and test cohorts of LUAD and LUSC. In addition, patients with LUAD in the low-risk group responded better to immunotherapy than those in the high-risk group. This study revealed two reliable immune-related-gene-signature models that were significantly associated with prognosis and tumor microenvironment cell infiltration in LUAD and LUSC, respectively. Evaluation of the integrated characterization of multiple immune-related genes and pathways could help to predict the response to immunotherapy and monitor immunotherapy strategies.


2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Ming Wu ◽  
Yu Xia ◽  
Yadong Wang ◽  
Fei Fan ◽  
Xian Li ◽  
...  

Abstract Purpose: Stomach adenocarcinoma (STAD) is one of the most common malignant tumors, and its occurrence and prognosis are closely related to inflammation. The aim of the present study was to identify gene signatures and construct an immune-related gene (IRG) prognostic model in STAD using bioinformatics analysis. Methods: RNA sequencing data from healthy samples and samples with STAD, IRGs, and transcription factors were analyzed. The hub IRGs were identified using univariate and multivariate Cox regression analyses. Using the hub IRGs, we constructed an IRG prognostic model. The relationships between IRG prognostic models and clinical data were tested. Results: A total of 289 differentially expressed IRGs and 20 prognostic IRGs were screened with a threshold of P&lt;0.05. Through multivariate stepwise Cox regression analysis, we developed a prognostic model based on seven IRGs. The prognostic model was validated using a GEO dataset (GSE 84437). The IRGs were significantly correlated with the clinical outcomes (age, histological grade, N, and M stage) of STAD patients. The infiltration abundances of dendritic cells and macrophages were higher in the high-risk group than in the low-risk group. Conclusions: Our results provide novel insights into the pathogenesis of STAD. An IRG prognostic model based on seven IRGs exhibited the predictive value, and have potential application value in clinical decision-making and individualized treatment.


2021 ◽  
Author(s):  
Ding Pan ◽  
Qi-Feng Ou ◽  
Pan-Feng Wu ◽  
Fang Yu ◽  
Ju-Yu Tang

Abstract Background:The incidence rate and mortality rate of melanoma have been increasing in recent decades. Increasing evidence has depicted the correlation between melanoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of melanoma.Methods:Gene expression profiling and clinical information of melanoma patients were derived from two public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. Results:Among 1,646 immune genes, a 25 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.80×10−22; hazard ratio [HR] =9.50 [6.04, 14.93]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=2.47×10−4; HR =2.99 [1.66, 5.38]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including keratinization and pigment phenotype-related pathways, enriched in the high-risk group. Macrophages M0, NK cells resting and T cells gamma delta were significantly higher in the high-risk group compared with the low-risk group. Conclusions:We successfully constructed a robust IRGPs signature with prognostic values for melanoma, providing new insights into post-operational treatment strategies.


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