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Significance of Tumor?-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

ABSTRACT: Objective:Increasing evidence has indicated an association between immune infiltration in colon cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of 22 tumor?-infiltrating immune cells (TIICs) on the prognosis of colon cancer patients. Methods:In our research, CIBERSORT algorithm was used to calculate the proportion of 22 TIICs in 369 colon cancer cases and 39 normal cases from the TCGA cohort. Cox regression analysis was used to analyze the effect of 22 TIICs on the prognosis of colon cancer. Immune risk scoring model was constructed based on the statistical correlation between TIICs subpopulation and survival. Meanwhile, multivariate ?Cox regression analysis was utilized to investigate whether the immune risk score model was an independent factor for predicting the prognosis of colon cancer. Nomogram was constructed to comprehensively predict the survival rate of colon cancer. P< 0.05 was considered to be statistically significant. Results:The results of the difference analysis showed that except for 12 TIICs, the remaining immune cells exhibited no differential infiltration between normal and colon cancer tissues (p<0. 05). Univariate ?Cox regression analysis revealed 5 immune cells statistically correlated with colon cancer?-related survival risk, including B cells naive, B cells memory, ?monocytes, ?macrophages M0, ?macrophages M1 (P<0.05). In addition, a four-cell based immune risk scoring model was constructed through LASSO Cox regression analysis. KM curve indicated that patients in highrisk were associated with poor outcomes (p<0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (AUC=0.848). Our model showed satisfying AUC and survival correlation in the validation dataset (3-year over survival (OS) AUC=0.941, 5-year OS AUC=0.865, P=0.022). Furthermore, multivariate ?Cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer (hazard ratio (HR) =5.017, 95% confidence interval (CI) =2.336-10.777; P<0.001). Ultimately, a nomogram was established to comprehensively predict the survival of colon cancer patients with the results of multivariate ?Cox regression analysis. Conclusion:Collectively, tumor?-infiltrating immune cells played an essential role in the prognosis of colon cancer. Furthermore, immune risk score was an independent predictive factor of colon cancer, indicating a poor survival.

SUBMITTER: Wu D

PROVIDER: S-EPMC7250301 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

Wu Dejun D Ding Yue Y Wang Tingfeng T Cui Peng P Huang Liangliang L Min Zhijun Z Xu Ming M

OncoTargets and therapy 20200522

<h4>Objective</h4>Increasing evidence has indicated an association between immune infiltration in colon cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of 22 tumor-infiltrating immune cells (TIICs) on the prognosis of colon cancer patients.<h4>Methods</h4>In our research, CIBERSORT algorithm was used to calculate the proportion of 22 TIICs in 369 colon cancer cases and 39 normal cases from the TCGA cohort. Cox regression analysis was used to a ...[more]

PMID: 32547088

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Project description:BackgroundThe complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration.MethodsThe differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman's correlation coefficients and p-values.ResultsIn two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant.ConclusionThese findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.

Project description:Objective:Increasing evidence has indicated an association between immune cells infiltration in LSCC and clinical outcome. The aim of this research was tantamount to comprehensively investigate the effect of 22 tumor infiltrating immune cells (TIICs) on the prognosis of LSCC patients. Methods:In our research, the CIBERSORT algorithm was utilized to calculate the proportion of 22 TIICs in 502 cases from the TCGA cohort. Cases with a CIBERSORT P-value of <0.05 were kept for further study. Using the CIBERSORT algorithm, we first investigated the difference of immune infiltration between normal tissue and LSCC in 22 subpopulations of immune cells. Kaplan-Meier analysis was used to analyze the effect of 22 TIICs on the prognosis of LSCC. An immune risk score model was constructed based on TIICs correlated with LSCC-related recurrence. Multivariate cox regression analysis was used to investigate whether the immune risk score was an independent factor for prognosis prediction of LSCC. Nomogram was under construction to comprehensively predict the survival rate of LSCC. Results:The results of the different analysis showed that except of memory B cells, naive CD4+T cells, T cells and activated NK cells, the remaining immune cells all had differential infiltration in normal tissues and LSCC (p < 0.05). Kaplan-Meier analysis revealed two immune cells statistically related to LSCC-related recurrence, including activated mast cells and follicular helper T cells. Immune risk score model was constructed based on three immune cells including resting memory CD4+T cells, activated mast cells and follicular helper T cells retained by forward stepwise regression analysis. The Kaplan-Meier curve indicated that patients in the high-risk group linked to poor outcome (P = 8.277e-03). ROC curve indicated that the immune risk score model was reliable in predicting recurrence risk (AUC = 0.614). Multivariate cox regression analysis showed that the immune risk score model was just an independent factor for prognosis prediction of LSCC (HR = 2.99, 95% CI [1.65-5.40]; P = 0.0002). The nomogram model combined immune risk score and clinicopathologic parameter score to predict 3-year survival in patients with LSCC. Conclusions:Collectively, tumor-infiltrating immune cells play a major role in the prognosis of LSCC.

Project description:Objective: Immune cells infiltrating has been proved to be associated with prognosis in gastric cancer (GC) by studies. This study aims to explore the prognosis value of infiltrating immune cells in gastric cancer. Methods: In our study, the CIBERSORT algorithm was used to calculate the fraction of 22 tumor-infiltrating immune cells (TIIC) in 100 normal and 300 tumor samples from the GEO cohort and 30 normal and 344 tumor samples from the TCGA cohort. Univariate and multivariate Cox regression were used to construct an immune risk score model. Multivariate cox regression was also used to validate whether our risk score model could predict prognosis in GC independently. Furthermore, the model was validated in different patient subgroups to test its independence. P<0.05 was considered statistically significant. Results: The results showed that the fraction of 3 immune cells increased in tumor tissues compared with normal tissues in both the GEO and TCGA cohort. Univariate cox regression analysis showed four cells significantly correlated with survival rate in GC (P<0.05). The immune risk score model was constructed based on the four cells through multivariate cox regression and further validated. The KM survival curve suggested that patients with high risk had poor prognosis than patients with low risk (P<0.05). ROC curve indicated the model was reliable (AUC= 0.67 in the GEO cohort, AUC = 0.65 in the TCGA cohort). Furthermore, multivariate Cox regression showed the model was an independent factor for overall survival predicting in GC (hazard ratio (HR) = 2.35, 95% confidence interval (CI) = 1.63~3.40 in the GEO cohort, HR = 2.87, 95% CI = 1.94~4.25 in the TCGA cohort). Finally, we validated the model in patient subgroups by the KM survival curve. Conclusion: In summary, tumor-infiltrating immune cells play an essential role in GC progression and affect the outcome of GC patients. The immune risk score can predict overall survival for GC independently, and high immune risk score is associated with poor prognosis.

Project description:BackgroundsThe high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved.MethodsUsing R software, we performed Kaplan-Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis.ResultsOn the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6.ConclusionB cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.

Project description:BackgroundLeft-sided and right-sided colon cancers (LCCs and RCCs, respectively) differ in their epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and prognosis. Notably, immune response gene expression profiles have been shown to differ between patients with LCC and patients with RCC. The immune system plays an important role in tumor immunosurveillance, and there is increasing evidence that peripheral blood immune cells have a profound influence on tumor prognosis. This study aimed to determine the clinical significance of circulating immune cells with respect to colon tumor locations.MethodsDifferent types of circulating immune cells were separated and analysed based on their surface markers by flow cytometry. We compared the numbers of dendritic cells (DCs) and T cell subsets in the peripheral blood of 94 patients with RCC or LCC and analysed the proportions of these immune cells in relation to tumor stage, tumor differentiation and lymphatic metastasis.ResultsWe show that at later tumor stages, patients with LCC had higher levels of circulating myeloid DCs (P = 0.049) and plasmacytoid DCs (P = 0.018) than patients with RCC. In poorly differentiated tumors, LCC patients had significantly higher amount of plasmacytoid DCs (P = 0.036), CD4+ memory T (Tm) cells (P = 0.012), CD4+ T cells (P = 0.028), Tm cells (P = 0.014), and regulatory T cells (P = 0.001) than RCC patients. The levels of circulating CD4+ T cells, Tm cells and CD4+ Tm cells were significantly elevated at later stages in patients with LCC or RCC, while these cells decreased in poorly differentiated tumors in patients with RCC. Moreover, CD4+ Tm cell and CD4+ T cell levels are significantly associated with lymph node metastasis in patients with LCC and RCC.DiscussionCirculating immune cells were associated with tumor location, tumor stage and tumor differentiation, and can be used to predict lymphatic metastasis in patients with colon cancer. This variation in systemic immunity could contribute to the differential prognosis of patients with colon cancer.

Project description:Background: ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality. Methods: Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes. Results: ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms. Conclusion: These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD.

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Significance of Tumor?-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

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Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

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Significance of Tumor?-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

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Significance of Tumor﻿-Infiltrating Immune Cells in the Prognosis of Colon Cancer.

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OmicsDI is part of the ELIXIR infrastructure

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Significance of Tumor-Infiltrating Immune Cells in the Prognosis of Colon Cancer.