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Effects of RNA Modification "Writers" of GALNT2 on the Tumor Microenvironment in Cervical Squamous Cell Carcinoma
1The Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha City, Hunan Province, China.
Abstract:
Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related deaths in women. RNA modification "writers" modulate and alter RNA molecular activity and have been implicated in the origin and development of cancer. We explored the effects of RNA modification writers on the tumor microenvironment in CESC and their prognostic value. RNA modification writers were altered at the genetic and transcriptional levels in CESC sample data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. A principal component analysis (PCA) score model was established based on the genes screened by Cox regression analysis and random forest dimensionality reduction. A survival analysis of CESC patients revealed significant differences between patients with high and low scores. The gene set variation analysis method was used for a functional enrichment analysis. The relative abundance of immune cells in CESCs was quantified using the CIBERSORT algorithm. There were significant differences in multiple signaling pathways and immune cells between the patients with high and low scores. Based on Genomics of Drug Sensitivity in Cancer data, we analyzed the genetic mutations in CESCs and predicted the therapeutic effects of multiple anticancer drugs. Patients with high scores showed significant resistance. Finally, the N-acetylgalactosaminyltransferase 2 (GALNT2) was highly expressed in CESCs and was associated with multiple immune cells and the formation of the extracellular matrix. PCA score based on RNA modification writers is closely associated with immune infiltration in the tumor microenvironment and could be used as a reference for prognosis and medication in CESC patients.
Insights
RNA modification writers impact the tumor microenvironment in cervical squamous cell carcinoma (CESC). A scoring system based on these writers predicts patient prognosis and drug response, highlighting GALNT2
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Cervical squamous cell carcinoma (CESC) is a leading cause of cancer death in women.
- RNA modification writers play a role in cancer development and progression.
- The impact of RNA modification writers on the CESC tumor microenvironment and prognosis is not well understood.
Purpose of the Study:
- To investigate the effects of RNA modification writers on the tumor microenvironment in CESC.
- To evaluate the prognostic value of RNA modification writers in CESC patients.
- To explore potential therapeutic targets and drug sensitivities related to RNA modification writers in CESC.
Main Methods:
- Analysis of RNA modification writer gene and transcript levels in CESC datasets (TCGA, GEO).
- Development of a Principal Component Analysis (PCA) score model using Cox regression and random forest.
- Survival analysis, gene set variation analysis (GSVA), CIBERSORT for immune cell quantification, and analysis of drug sensitivity data (GDSC).
Main Results:
- Significant differences in signaling pathways and immune cell infiltration were observed between high and low PCA score groups.
- Patients with high PCA scores exhibited significant resistance to multiple anticancer drugs.
- N-acetylgalactosaminyltransferase 2 (GALNT2) was highly expressed in CESC and associated with immune cells and extracellular matrix formation.
Conclusions:
- The PCA score derived from RNA modification writers is closely linked to immune infiltration within the CESC tumor microenvironment.
- This scoring system can serve as a valuable reference for predicting prognosis and guiding medication choices in CESC patients.
- GALNT2 represents a potential therapeutic target in CESC, warranting further investigation.
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