Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Dai, Longfei; Wang, Xu; Bai, Tao; Li, Jianjun; Chen, Bin; Li, Ting; Yang, Wenqi

doi:10.3389/fgene.2022.961554

Cited by 4 publications

(1 citation statement)

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“…By integrating these and other datasets developers performed a systems biology analysis of cell senescence. At present, there are few studies on CSRGs in ECa, but a number of studies have shown that CSRGs signature can play a prognostic role in hepatocellular carcinoma, gastric cancer, bladder cancer, renal cell carcinoma, and colon cancer (17)(18)(19)(20)(21). However, the expression characteristics and prognostic significance of CSRGs in ECa remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes

Wang,

Dai,

Huang

et al. 2023

Front. Oncol.

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BackgroundCellular senescence occurs throughout life and can play beneficial roles in a variety of physiological processes, including embryonic development, tissue repair, and tumor suppression. However, the relationship between cellular senescence-related genes (CSRGs) and immunotherapy in esophageal carcinoma (ECa) remains poorly defined.MethodsThe data set used in the analysis was retrieved from TCGA (Research Resource Identifier (RRID): SCR_003193), GEO (RRID: SCR_005012), and CellAge databases. Data processing, statistical analysis, and diagram formation were conducted in R software (RRID: SCR_001905) and GraphPad Prism (RRID: SCR_002798). Based on CSRGs, we used the TCGA database to construct a prognostic signature for ECa and then validated it in the GEO database. The predictive efficiency of the signature was evaluated using receiver operating characteristic (ROC) curves, Cox regression analysis, nomogram, and calibration curves. According to the median risk score derived from CSRGs, patients with ECa were divided into high- and low-risk groups. Immune infiltration and immunotherapy were also analyzed between the two risk groups. Finally, the hub genes of the differences between the two risk groups were identified by the STRING (RRID: SCR_005223) database and Cytoscape (RRID: SCR_003032) software.ResultsA six-gene risk signature (DEK, RUNX1, SMARCA4, SREBF1, TERT, and TOP1) was constructed in the TCGA database. Patients in the high-risk group had a worse overall survival (OS) was disclosed by survival analysis. As expected, the signature presented equally prognostic significance in the GSE53624 cohort. Next, the Area Under ROC Curve (AUC=0.854) and multivariate Cox regression analysis (HR=3.381, 2.073-5.514, P<0.001) also proved that the risk signature has a high predictive ability. Furthermore, we can more accurately predict the prognosis of patients with ECa by nomogram constructed by risk score. The result of the TIDE algorithm showed that ECa patients in the high-risk group had a greater possibility of immune escape. At last, a total of ten hub genes (APOA1, MUC5AC, GC, APOA4, AMBP, FABP1, APOA2, SOX2, MUC8, MUC17) between two risk groups with the highest interaction degrees were identified. By further analysis, four hub genes (APOA4, AMBP, FABP1, and APOA2) were related to the survival differences of ECa.ConclusionsOur study reveals comprehensive clues that a novel signature based on CSRGs may provide reliable prognosis prediction and insight into new therapy for patients with ECa.

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Section: Introductionmentioning

confidence: 99%

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes

Wang,

Dai,

Huang

et al. 2023

Front. Oncol.

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BMAP-27 Peptide Reduces Proliferation and Increases Apoptosis in Primary and Metastatic Colon Cancer Cell Lines

Das,

Deka,

Baildya

et al. 2023

Int J Pept Res Ther

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BMAP-27 peptide is reported to possess apoptotic and anti-proliferative effects against cancer cells but the actual mechanism of action is yet to be investigated. In the current investigation, we aimed to study the role of the BMAP-27 peptide in reducing proliferation and increasing apoptosis in colon cancer cell lines. In this study, we used primary and metastatic colon cancer cell lines SW480 and SW620. Cell proliferation was measured using MTT and CCK-8 assays, and cellular damage was analyzed by lactate dehydrogenase assay. Apoptosis, cell cycle, and proliferation potentials were measured by the expression of CASPASE3, BAX, BCL-2, TP53, CDK-6, PCNA, WNT11, AXIN1, and CTNNB1 genes. Additionally, in-silico studies were conducted to determine the binding affinities of BMAP-27 with adenomatous polyposis coli (APC) and β-catenin proteins, one of the primary regulators of colon cancer. BMAP-27 peptide reduced colon cancer cell proliferation, upregulated tumor suppressor genes CASPASE3, BAX, TP53, AXIN1 expression, and downregulated the expression of oncogenes BCL-2, CDK-6, PCNA, WNT11, CTNNB1 in both the cell lines, however, in the primary colon cancer cell line the changes are found to be more significant. The molecular dynamic simulation analysis revealed substantial binding affinity of the peptide to APC and β-catenin proteins. BMAP-27 peptide significantly inhibited the proliferation and induced apoptosis in the primary colon cancer cell line than in the metastatic colon cancer cell line. In-silico results suggest that BMAP-27 shows a strong binding affinity with APC and β-catenin proteins, highlighting its role in inhibiting colon cancer cell proliferation.

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Prognostic cellular senescence-related lncRNAs patterns to predict clinical outcome and immune response in colon cancer

Cao,

Chen,

et al. 2024

Front. Immunol.

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BackgroundCellular 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.MethodsThe 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.ResultsThree 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.ConclusionCSRLs 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.

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Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Cited by 4 publications

References 53 publications

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes

BMAP-27 Peptide Reduces Proliferation and Increases Apoptosis in Primary and Metastatic Colon Cancer Cell Lines

Prognostic cellular senescence-related lncRNAs patterns to predict clinical outcome and immune response in colon cancer

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