Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy

May 16, 2025Journal of immunotherapy (Hagerstown, Md. : 1997)

Using Calmodulin-Related Genes to Predict Outcomes and Study Immune Cells and Drug Responses in Esophageal Squamous Cell Carcinoma

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Abstract

A prognosis model based on 4 feature genes demonstrates excellent predictive capability for esophageal squamous cell carcinoma (ESCC).

Four feature genes—ATP2B3, CALB1, KCNQ1, and MYO1G—were identified as significant in the prognostic model.
ATP2B3 and KCNQ1 were significantly downregulated in human ESCC cells, while CALB1 and MYO1G were upregulated (P < 0.05).
Single-cell analysis revealed that MYO1G and KCNQ1 were primarily expressed in distinct cellular clusters.
The risk model showed strong associations with functional pathway enrichment, immune cell infiltration, and somatic mutations.
AZD-8055 may represent a potential therapy for ESCC patients, with evidence of favorable binding stability to MYO1G.

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Calmodulin (CALM) has a bearing on the prognosis of various cancers. However, the prognostic value of CALM in esophageal squamous cell carcinoma (ESCC) remains unelucidated. Differentially expressed genes (DEGs) were screened between normal and tumor groups of TCGA-ESCC sets. The intersection of DEGs with calmodulin-related genes (CRGs) yielded differentially expressed CRGs (DE-CRGs). A prognostic model was established using LASSO Cox regression analysis and multivariate Cox regression analysis. qPCR validated the expression of prognostic feature genes. Analysis of gene expression patterns of different cellular clusters was based on single-cell sequencing data. Lastly, GSEA enrichment, immune infiltration, mutational profiling, drug sensitivity, and molecular docking as well as cellular thermal shift assay (CETSA) were conducted for ESCC patients. A prognosis model with excellent predictive capability was created based on 4 feature genes (ATP2B3, CALB1, KCNQ1, and MYO1G). The qPCR results demonstrated that ATP2B3 and KCNQ1 were significantly downregulated in human ESCC cells, whereas CALB1 and MYO1G were upregulated ( P <0.05). Single-cell analysis uncovered that MYO1G and KCNQ1 were mainly expressed in different cell clusters. Furthermore, this risk model was strongly associated with functional pathway enrichment, immune cell infiltration, and somatic mutations. We also identified AZD-8055 may be potential therapy for ESCC patients. The CETSA experiment demonstrated the existence of a favorable binding thermal stability between AZD-8055 and MYO1G. This research may identify potential biomarkers for predicting the prognosis of ESCC patients.

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Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy

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