Abstract
Cervical cancer (CC) remains a prevalent gynecological malignancy, posing a significant health burden among women worldwide. With the remarkable discoveries of cellular pyroptosis and cuproptosis, there has been a growing focus on exploring the intricate relationship between these two forms of cell death and their impact on tumor progression. In recent years, alternative splicing has emerged as a significant field in cancer research. Thus, the integration of alternative splicing, pyroptosis, and cuproptosis holds immense value in studying their collective impact on the occurrence and progression of cervical cancer. In this study, alternative splicing data of pyroptosis- and cuproptosis-associated genes were integrated with public databases, including TCGA, to establish a prognostic model for cervical cancer based on COX regression modeling. Subsequently, the tumor microenvironment (TME) phenotypes in the high-risk and low-risk patient groups were characterized through a comprehensive bioinformatics analysis. The findings of this study revealed that the low-risk group exhibited a predominant immune-active TME phenotype, while the high-risk group displayed a tumor-favoring metabolic phenotype. These results indicate that the alternative splicing of pyroptosis- and cuproptosis-associated genes plays a pivotal role in remodeling the phenotypic landscape of the cervical cancer TME by modulating immune responses and metabolic pathways. This study provides valuable insights into the interplay between alternative splicing variants involved in pyroptosis and cuproptosis and the TME, contributing to a deeper understanding of cervical cancer pathogenesis and potential therapeutic avenues.
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Data Availability
The data used in this study could be accessed from freely public-accessible database including databases of TCGA (https://portal.gdc.cancer.gov/), Molecular Signatures (https://www.gsea-msigdb.org/gsea/msigdb/), and TCGA SpliceSeq (https://bioinformatics.mdanderson.org/TCGASpliceSeq/).
Code Availability
Raw data and codes are available on request.
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The databases of TCGA and websites used in this work are open free to the public, the data of patients deposited in TCGA have obtained ethical approval, and this study is based on open-source data, so there are no ethical issues and other conflicts of interest.
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Supplementary Information
Supplementary Figure 1
Correlation analysis of tumor-infiltrating immune cells (TICs) and risk score. (PNG 380 kb)
Supplementary Figure 2
Correlation analysis of immune checkpoint-associated genes and risk score. (PNG 683 kb)
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Bi, K., Yang, J. & Wei, X. Alternative splicing variants involved in pyroptosis and cuproptosis contribute to phenotypic remodeling of the tumor microenvironment in cervical cancer. Reprod. Sci. 30, 3648–3660 (2023). https://doi.org/10.1007/s43032-023-01284-y
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DOI: https://doi.org/10.1007/s43032-023-01284-y