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Updated: Sep 23, 2025

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
A Systematic Pan-Cancer Analysis of CASP3 as a Potential Target for Immunotherapy
Zheng Zhou1,2, Shiying Xu1,3, Liehao Jiang1,3
1Department of Head and Neck Surgery, Centre of Otolaryngology-head and Neck Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Abstract:
CASP3 is the gene encoding caspase-3, a specific protease that cleaves substrates such as poly-ADP ribose polymerase and acetyl-DEVD-7-amino-4-methylcoumarin. This enzymatic activity leads to DNA fragmentation, which is a hallmark of apoptosis. Although recent studies have demonstrated that CASP3 plays a vital role in tumour suppression by promoting apoptosis, these reports did not consider systematic pan-cancer analyses. Therefore, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse CASP3 expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden (TMB), and microsatellite instability (MSI), as well as immune cell infiltration in different tumours and the molecular mechanisms underlying these. We found that CASP3 expression was significantly associated with the prognosis of most tumours. Additionally, promoter methylation status was associated with CASP3 expression in bladder urothelial carcinoma, oesophageal carcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, sarcoma, testicular germ cell tumours, and uterine corpus endometrial carcinoma. TMB and MSI were associated with CASP3 expression in 15 tumours. Moreover, CASP3 expression was correlated with the tumour microenvironment in nearly all tumour types. Further, we observed that in addition to apoptosis, CASP3 action plausibly involves B cell activation, antigen presentation, immune responses, chemokine receptors, and inflammatory function. Our study thus provides a relatively comprehensive understanding of the carcinogenicity of CASP3 in different tumours and suggests that CASP3 is a potential prognostic marker.
Insights
The CASP3 gene, encoding caspase-3, is crucial for apoptosis and tumor suppression. Pan-cancer analysis reveals CASP3 expression impacts prognosis, methylation, TMB, MSI, and the tumor microenvironment across many cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Caspase-3 (CASP3) is a key protease in apoptosis, essential for DNA fragmentation.
- CASP3's role in tumor suppression via apoptosis is established, but comprehensive pan-cancer analyses are lacking.
Purpose of the Study:
- To conduct a systematic pan-cancer analysis of CASP3 expression.
- To investigate the relationship between CASP3 and cancer prognosis, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases.
- Analyzed CASP3 expression in relation to clinicopathological features and molecular subtypes across various cancer types.
Main Results:
- CASP3 expression significantly correlates with prognosis in most tumors.
- Promoter methylation of CASP3 is linked to its expression in several specific cancers.
- CASP3 expression is associated with TMB and MSI in 15 tumor types.
- CASP3 correlates with the tumor microenvironment and immune functions, including B cell activation and antigen presentation.
Conclusions:
- CASP3 expression is a significant prognostic factor across diverse cancers.
- CASP3's functions extend beyond apoptosis to immune responses and inflammation.
- CASP3 represents a potential pan-cancer prognostic biomarker.

