Identification of Molecular Subtypes Associated with PCD in Esophageal Squamous Cell Carcinoma and Analysis of Immune Microenvironment

Min Chen; Yijun Qi; Shenghua Zhang; Yubo Du; Haodong Cheng; Shegan Gao

doi:10.2174/0109298673305351240507060832

Identification of Molecular Subtypes Associated with PCD in Esophageal Squamous Cell Carcinoma and Analysis of Immune Microenvironment

Curr Med Chem. 2024 May 10. doi: 10.2174/0109298673305351240507060832. Online ahead of print.

Authors

Min Chen^{1

2

3

4

5

6

7}, Yijun Qi^{2

3

4

5

6

7}, Shenghua Zhang^{2

3

4

5

6

7}, Yubo Du^{2

3

4

5

6

7}, Haodong Cheng^{2

3

4

5

6

7}, Shegan Gao^{1

2

3

4

5

6

7}

Affiliations

¹ School of Information Engineering, Henan University of Science and Technology, Luoyang, 471023, China.
² State Key Laboratory of Esophageal Cancer Prevention and Treatment, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China.
³ Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China.
⁴ Henan Key Laboratory of Cancer Epigenetics, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China.
⁵ Cancer Hospital, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China.
⁶ College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471023, China.
⁷ Medical College of Henan University of Science and Technology, Luoyang, 471023, China.

PMID: 38738730
DOI: 10.2174/0109298673305351240507060832

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a highly fatal malignancy with increasing incidence, and programmed cell death (PCD) plays an important role in homeostasis.

Aims: This study aimed to explore the ESCC of heterogeneity based on the PCD signatures for the diagnosis and treatment of patients.

Methods: The clinical information and RNA-seq data of patients with ESCC and the PCD-related genes set were used to identify PCD signatures.The "limma" package was used to identify the differentially expressed genes (DEGs). "Clusterprofiler" package was used for function enrichment analysis, and the "ConsensusClusterPlus" package was performed for consensus clustering. Finally, the "GSVA" package and the Cibersort algorithm were used for the immune infiltration analysis.

Results: We performed differential expression analysis between ESCC and normal samples and identified 1659 DEGs, of which 124 DEGs were PCD genes. Then, the patients were divided into cluster1 and cluster2 based on the expression of 124 PCD genes. There was a significant difference in immune infiltration between the two clusters. The patients in cluster 1 had a higher immune score and more CD56dim natural killer cells, monocytes, activated CD4 T cells, eosinophil, and activated B cells infiltration, while cluster2 had a higher stromal score, more immune regulation, and immune checkpoint genes expression.

Conclusion: We identified two clusters based on PCD gene expression and characterized their tumor microenvironment and immune checkpoint difference. Our findings may provide some new insight into the treatment of ESCC.

Keywords: Esophageal squamous cell carcinoma (ESCC); consensus clustering; enrichment analysis; immune infiltration; programmed cell death (PCD)-related signature; variation landscape..