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Identification of m6A‐related lncRNAs as prognostic signatures. (A) Volcano plot on all DELs between tumors and normal samples. The green dots represent downregulated lncRNAs, while the red dots represent upregulated lncRNAs. (B) Statistical differences between normal and tumor groups were compared through the unpaired t test. The p values are labeled above each boxplot with asterisks. (*p < .05, **p < .01, ***p < .001, ****p < .0001). (C) The optimal values of the penalty parameter λ were determined by cross‐validation. (D) LASSO coefficient profiles of the 11 lncRNAs were related with prognosis. (E) Forest plot showing the results of the multivariate Cox analysis. (F) The distribution of the high‐ and low risk score groups and its relationship with OS, and the expression pattern of 11 prognostic signatures in high‐ and low risk score groups. (G) Kaplan–Meier curve revealed that OS in the low‐risk score group was significantly higher than that in the high‐risk score group. (H) Time‐dependent ROC curve analysis of the m6A‐related risk score model.
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Background:
The current study probed prognosis-related potential for m6A-related lncRNAs signatures within colon tumor immune microenvironment (TIM).
Methods:
After downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A-relat...
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Background: Colon cancer (CC) is a prevalent malignant tumor that affects people all around the world. In this study, N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) in 473 colon cancers and 41 adjacent tissues of CC patients from The Cancer Genome Atlas (TCGA) were investigated.
Method: The Pearson correlation analysis was c...
Citations
... Zhao et al., 2022, identified AC007743.1 as one of six lncRNAs that are associated with necroptosis, and which are independent prognostic predictors of clear cell renal cell carcinoma [106]. In 2023, Cao et al. highlighted AC007743.1 as a prognostic lncRNA for colon cancer [107]. We observed that AC007743.1 was upregulated in AF men (q ≤ 0.1 and fold change ≥ 1.5), however, in AF men who received vitamin D supplements, AC007743.1 was downregulated (q ≤ 0.4 and fold change of ≥ 1.5), suggesting the potential antiinflammatory effects of vitamin D supplementation in AF PC patients. ...
Background/Objectives: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, and one which displays significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to those of EU and assess their involvement in immune response and inflammation. Methods: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA–mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting their potential regulatory roles in immune response and inflammation. Results: Key lncRNAs specific to AF men were identified, with several being implicated for immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on antigen processing and presentation, chemokine signaling, and ribosome pathways, suggesting their critical roles in immune regulation. Conclusions: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes.
... and AC007128.1, play a substantial role in the progression of colon cancer [87]. ...
Cytotoxic T lymphocyte antigen 4 (CTLA-4), in conjunction with PD-1 and CD28, plays a pivotal role in the modulation of T-cell activation. Specifically, CTLA-4 exerts its influence by impeding the generation of IL-2 and the proliferation of T cells. CTLA-4, being a receptor with a high affinity, engages in competitive binding with CD28 for the interaction with primary T-cell activator molecules, specifically CD80 and CD86. The appropriate functioning of T-cell activation is contingent upon maintaining a precise equilibrium between CTLA-4 and CD28. Consequently, any disruption in the expression of CTLA-4 significantly enhances the risk for a range of severe ailments, such as cancer, infectious diseases, allergies, and notably autoimmune diseases. The significance of epigenetic regulation of CTLA-4, particularly through non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has considerable weight within this particular framework. To date, there have been associations shown between various abnormalities in the expression of ncRNAs that regulate CTLA-4 and clinicopathological characteristics. Nevertheless, it is evident that there is a lack of a comprehensive investigation. Hence, the present work was undertaken to summarize the existing research on the epigenetic control of CTLA-4, with a primary emphasis on elucidating the regulatory procedures, biological processes, and clinical applications in human diseases. The objective of this review is to acquire a thorough comprehension of the relationship between RNA/lncRNA/miRNA/mRNA (CTLA-4) and its role in the progression of diverse human disorders.
... Then, venn diagram was used to show overlapping CS-related DEGs between DEGs and CS-related genes. Pearson correlation analysis was performed based on CS-related DEGs and lncRNAs expression levels to identify CSRLs with |Pearson correlation coefficient| > 0.5 and P-value of < 0.001 (28,29). ...
... Then a CSRLs prognostic model was established by applying multivariate Cox regression analysis. The formula for the CSRLs prognostic model was built to forecast patient survival (28): ...
Background
Cellular senescence (CS) is believed to be a major factor in the evolution of cancer. However, CS-related lncRNAs (CSRLs) involved in colon cancer regulation are not fully understood. Our goal was to create a novel CSRLs prognostic model for predicting prognosis and immunotherapy and exploring its potential molecular function in colon cancer.
Methods
The mRNA sequencing data and relevant clinical information of GDC TCGA Colon Cancer (TCGA-COAD) were obtained from UCSC Xena platform, and CS-associated genes was acquired from the CellAge website. Pearson correlation analysis was used to identify CSRLs. Then we used Kaplan–Meier survival curve analysis and univariate Cox analysis to acquire prognostic CSRL. Next, we created a CSRLs prognostic model using LASSO and multivariate Cox analysis, and evaluated its prognostic power by Kaplan–Meier and ROC curve analysis. Besides, we explored the difference in tumor microenvironment, somatic mutation, immunotherapy, and drug sensitivity between high-risk and low-risk groups. Finally, we verified the functions of MYOSLID in cell experiments.
Results
Three CSRLs (AC025165.1, LINC02257 and MYOSLID) were identified as prognostic CSRLs. The prognostic model exhibited a powerful predictive ability for overall survival and clinicopathological features in colon cancer. Moreover, there was a significant difference in the proportion of immune cells and the expression of immunosuppressive point biomarkers between the different groups. The high-risk group benefited from the chemotherapy drugs, such as Teniposide and Mitoxantrone. Finally, cell proliferation and CS were suppressed after MYOSLID knockdown.
Conclusion
CSRLs are promising biomarkers to forecast survival and therapeutic responses in colon cancer patients. Furthermore, MYOSLID, one of 3-CSRLs in the prognostic model, could dramatically regulate the proliferation and CS of colon cancer.
... Unlike other previous LPS-related prognostic models [40,41], our 5-TALRGs signature contained the smallest number of genes and was relatively easy to apply clinically. As with other good prognostic signatures [42,43], we also established a nomogram with better accuracy to contribute to predicting the prognosis of CRC using age, sex, microsatellite status, pathological stage, and risk score. Besides, TALRGs signature had a good performance in understanding immunological properties for CRC. ...
Purpose:
The intratumoral microorganisms participates in the progression and immunotherapy of colorectal cancer (CRC). However, due to technical limitations, the impact of microorganisms on CRC has not been fully understood. Therefore, we conducted a systematic analysis of relationship between bacterial lipopolysaccharide (LPS)-associated genes and immune cells to explore new biomarkers for predicting the prognosis of CRC.
Methods:
The single-cell RNA sequencing data and the Comparative Toxicogenomics Database were used to screen T cells-associated LPS-related genes (TALRGs). Then, we established and validated the TALRGs risk signature in The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort and GSE39582 cohort. Besides, we compared the differences in tumor-infiltrating immune cell types, immunotherapeutic response, somatic mutation profiles, and tumor mutation burden (TMB) between high-risk group and low-risk group. In addition, the immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent was performed to explore the potential value of the TALRGs signature on immunotherapy.
Results:
Five prognostic TALRGs were identified and selected to build the prognostic model. The high-risk group had poor prognosis in both TCGA-COAD cohort (P < 0.0001) and GSE39582 cohort (P = 0.00019). The areas under the curves (AUCs) of TALRGs signature were calculated (TCGA-COAD cohort: 0.624 at 1 years, 0.639 at 3 years, 0.648 at 5 years; anti-PD-L1 cohort was 0.59). The high-risk group had advanced pathological stages and higher TMN stages in both TCGA-COAD cohort and GSE39582 cohort. The high-risk group had the higher infiltration of immunosuppressive cells, the expressions of immune checkpoint molecules, the IC50 values of chemotherapy drugs, and TP53 mutation rate (P < 0.05). In addition, patients with high TMB had worse prognosis (P < 0.05). Furthermore, the Imvigor210 also showed patients with high-risk scores had poor prognosis (platinum-treated cohort: P = 0.0032; non-platinum-treated cohort: P = 0.00017).
Conclusions:
Microorganisms are closely related to the tumor microenvironment to influence the progression and immune response of CRC via stimulating T cells through LPS-related genes. The TALRGs signature contributed to predict the prognosis and immunotherapy of CRC, and became new therapeutic targets and biomarkers of CRC.
