Dataset Information

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

ABSTRACT:

Background

The 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.

Methods

The 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.

Results

In 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.

Conclusion

These 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.

SUBMITTER: Bao D

PROVIDER: S-EPMC7886994 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

Bao Dandan D Zhang Chenghao C Li Longlong L Wang Haihong H Li Qiuyan Q Ni Leilei L Lin Yinfeng Y Huang Rong R Yang Zhangwei Z Zhang Yan Y Hu Yiren Y

Frontiers in oncology 20210203

<h4>Background</h4>The 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.<h4>Methods</h4>The differential expression of complements was explored <i>via</i> ...[more]

PMID: 33614473

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Project description:BackgroundGastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer-associated mortality worldwide. The tumor microenvironment, especially tumor-infiltrating immune cells (TIICs), exhibits crucial roles both in promoting and inhibiting cancer growth. The aim of the present study was to evaluate the landscape of TIICs and develop a prognostic nomogram in GC.Materials and methodsA gene expression profile obtained from a dataset from The Cancer Genome Atlas (TCGA) was used to quantify the proportion of 22 TIICs in GC by the CIBERSORT algorithm. LASSO regression analysis and multivariate Cox regression were applied to select the best survival-related TIICs and develop an immunoscore formula. Based on the immunoscore and clinical information, a prognostic nomogram was built, and the predictive accuracy of it was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration plot. Furthermore, the nomogram was validated by data from the International Cancer Genome Consortium (ICGC) dataset.ResultsIn the GC samples, macrophages (25.3%), resting memory CD4 T cells (16.2%) and CD8 T cells (9.7%) were the most abundant among 22 TIICs. Seven TIICs were filtered out and used to develop an immunoscore formula. The AUC of the prognostic nomogram in the TCGA set was 0.772, similar to that in the ICGC set (0.730) and whole set (0.748), and significantly superior to that of TNM staging alone (0.591). The calibration plot demonstrated an outstanding consistency between the prediction and actual observation. Survival analysis revealed that patients with GC in the high-immunoscore group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the immunoscore was an independent prognostic factor.DiscussionThe immunoscore could be used to reinforce the clinical outcome prediction ability of the TNM staging system and provide a convenient tool for risk assessment and treatment selection for patients with GC.

Dataset Information

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

Background

Methods

Results

Conclusion

Publications

Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer.

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