Identification of a pyroptosis-related lncRNA risk model for predicting prognosis and immune response in colon adenocarcinoma

Tan, Yuying; Lu, Liqing; Liang, Xujun; Chen, Yongheng

doi:10.1186/s12957-022-02572-8

Cited by 5 publications

(5 citation statements)

References 49 publications

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“…Moreover, the TME related signatures analysis revealed that CD8 T cell effector and immune checkpoint associated pathway genes were higher in the low‐risk group than in the high‐risk group (Figure 5C). Previous studies revealed that colon adenocarcinoma patients with a higher immune score and more infiltration of antitumor immune cells have a better survival outcome 17–19 . Therefore, we speculated that the better prognosis of the low‐risk group might be related to the more favorable antitumor immune microenvironment.…”

Section: Resultsmentioning

confidence: 90%

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Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression

Luo

Chen

et al. 2022

Cancer Science

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Colon cancer is the third most common cancer and the second leading cause of cancer‐related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2‐like kinase 1(CLK1), CLK2, and A‐kinase anchor protein 8‐like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low‐risk group, and TME‐related pathway gene expression was also higher in low‐risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.

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Section: Resultsmentioning

confidence: 90%

“…Previous studies revealed that colon adenocarcinoma patients with a higher immune score and more infiltration of antitumor immune cells have a better survival outcome. 17 , 18 , 19 Therefore, we speculated that the better prognosis of the low‐risk group might be related to the more favorable antitumor immune microenvironment.…”

Section: Resultsmentioning

confidence: 99%

Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression

Luo

Chen

et al. 2022

Cancer Science

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“…In our current work, we found that there was a clear link between the hypoxia score and the amount of COPZ1 in several cancers. Previous studies revealed that a higher immune score was correlated with better survival outcomes [ 45 , 46 ]. We further discovered that the infiltration of antitumor immune cells was higher in the patients with low COPZ1 expression, such as B cells, Neutrophil, CD8+T cells, CD4+T cells and M1 macrophages.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Hong

Xia

Sun

et al. 2023

Genes

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The Coatomer protein complex Zeta 1 (COPZ1) has been reported to play an essential role in maintaining the survival of some types of tumors. In this study, we sought to explore the molecular characteristics of COPZ1 and its clinical prognostic value through a pan-cancers bioinformatic analysis. We found that COPZ1 was extremely prevalent in a variety of cancer types, and high expression of COPZ1 was linked to poor overall survival in many cancers, while low expression in LAML and PADC was correlated with tumorigenesis. Besides, the CRISPR Achilles’ knockout analysis revealed that COPZ1 was vital for many tumor cells’ survival. We further demonstrated that the high expression level of COPZ1 in tumors was regulated in multi-aspects, including abnormal CNV, DNA-methylation, transcription factor and microRNAs. As for the functional exploration of COPZ1, we found a positive relationship between COPZ1’s expression and stemness and hypoxia signature, especially the contribution of COPZ1 on EMT ability in SARC. GSEA analysis revealed that COPZ1 was associated with many immune response pathways. Further investigation demonstrated that COPZ expression was negatively correlated with immune score and stromal score, and low expression of COPZ1 has been associated to more antitumor immune cell infiltration and pro-inflammatory cytokines. The further analysis of COPZ1 expression and anti-inflammatory M2 cells showed a consistent result. Finally, we verified the expression of COPZ1 in HCC cells, and proved its ability of sustaining tumor growth and invasion with biological experiments. Our study provides a multi-dimensional pan-cancer analysis of COPZ and demonstrates that COPZ1 can serve as both a prospective target for the treatment of cancer and a prognostic marker for a variety of cancer types.

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“…Several recent studies have proposed prognostic models for COAD [22][23][24]. However, the studies' predictive performances have not been validated in COAD, and the differences in immune infiltrating cells and immune checkpoint blockade-, immune checkpoint-, and m6A-related genes between the high and low risks of the prediction model were not analyzed.…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of Pyroptosis-Related lncRNA Prediction Model for Colon Adenocarcinoma and Immune Infiltration Analysis

et al. 2022

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Objective Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide. However, the pyroptosis-related lncRNAs of COAD have not been deeply examined and validated. Here, we constructed and validated a risk model on pyroptosis-related lncRNAs in COAD. Methods The RNA sequencing transcriptome and clinical data of COAD patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed pyroptosis-related mRNAs and mRNA-lncRNA coexpression network were identified. After univariate and multifactorial cox analyses of prognosis-related lncRNAs, a risk model was constructed. Next, we analyzed the differences in immune infiltration, immune checkpoint blockade-, immune checkpoint-, and N6-methyladenosine-related gene expressions between the high- and low-risk groups. RT-qPCR was used to validate the expression of lncRNAs. Result A risk model was constructed based on 9 pyroptosis-related lncRNAs and separated COAD patients into the high- and low-risk groups. Immune infiltration analysis and immune checkpoint blockade-, immune checkpoint-, and N6-methyladenosine-related genes showed significant differences between the two subgroups. RT-qPCR showed that the 9 pyroptosis-related lncRNAs could be used as prognostic indicators. Conclusion A novel risk model based on pyroptosis-related lncRNAs was constructed and demonstrated that these lncRNAs might be used as independent prognostic biomarkers. This will also assist shed light on the COAD prognosis and therapy.

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Identification of a pyroptosis-related lncRNA risk model for predicting prognosis and immune response in colon adenocarcinoma

Cited by 5 publications

References 49 publications

Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression

Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression

A Comprehensive Pan-Cancer Analysis of the Regulation and Prognostic Effect of Coat Complex Subunit Zeta 1

Construction and Validation of Pyroptosis-Related lncRNA Prediction Model for Colon Adenocarcinoma and Immune Infiltration Analysis

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