Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms

Abstract Esophageal cancer is a grave malignant condition. While radiotherapy, often in conjunction with chemotherapy, serves as a cornerstone in the management of locally advanced or metastatic cases, patient tolerance and treatment resistance frequently hinder its efficacy. Cell-in-cell structures...

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Main Authors: Wei Cao, Dacheng Jin, Weirun Min, Haochi Li, Rong Wang, Jinlong Zhang, Yunjiu Gou
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-13483-8
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author Wei Cao
Dacheng Jin
Weirun Min
Haochi Li
Rong Wang
Jinlong Zhang
Yunjiu Gou
author_facet Wei Cao
Dacheng Jin
Weirun Min
Haochi Li
Rong Wang
Jinlong Zhang
Yunjiu Gou
author_sort Wei Cao
collection DOAJ
description Abstract Esophageal cancer is a grave malignant condition. While radiotherapy, often in conjunction with chemotherapy, serves as a cornerstone in the management of locally advanced or metastatic cases, patient tolerance and treatment resistance frequently hinder its efficacy. Cell-in-cell structures, prevalent in various tumors, have been linked to prognosis. Hence, investigating the prognostic significance and regulatory mechanisms of genes related to these intracellular structures in esophageal cancer is imperative. The Cancer Genome Atlas (TCGA) Esophageal Cancer (ESCA) dataset served as the training set for the analysis. Differentially expressed genes (DEGs) in ESCA samples were identified, with those related to intercellular structures designated cell-in-cell-related differential expression genes (CIC-related DEGs). Cox regression analysis was employed to identify prognostic genes, categorizing samples into high- and low-risk groups based on median risk scores. Validation was conducted using the GSE53624 risk model. Established methodologies included morphological mapping, enrichment analysis, immune infiltration analysis, prognostic gene expression validation, molecular docking, and Reverse Transcription Polymerase Chain Reaction (RT-PCR) validation. Thirty-eight intersecting genes were identified between the disease and normal groups in ESCA samples. Stepwise multivariate Cox analysis pinpointed three prognostic genes: androgen receptor (AR), C-X-C motif chemokine ligand 8 (CXCL8), and epidermal growth factor receptor (EGFR). The risk model’s applicability was confirmed in the GSE53624 dataset, revealing eight significantly different immune-related gene sets. Prognostic gene expression validation demonstrated significant differences between the disease and normal groups in both datasets. The proteins corresponding to the three prognostic genes interacted with gefitinib and osimertinib. RT-PCR results corroborated the differential expression of prognostic genes in esophageal cancer tissues. This study identified AR, CXCL8, and EGFR as prognostic genes and demonstrated their molecular interactions with gefitinib and osimertinib, providing a foundation for ESCA diagnosis and treatment.
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spelling doaj-art-40d4f9187bcd459e844e29c6f41c75632025-01-26T12:37:46ZengBMCBMC Cancer1471-24072025-01-0125111510.1186/s12885-025-13483-8Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanismsWei Cao0Dacheng Jin1Weirun Min2Haochi Li3Rong Wang4Jinlong Zhang5Yunjiu Gou6First Clinical Medical School, Gansu University of Chinese MedicineChest Clinic Center, Gansu Provincial People’s HospitalFirst Clinical Medical School, Gansu University of Chinese MedicineFirst Clinical Medical School, Gansu University of Chinese MedicineFirst Clinical Medical School, Gansu University of Chinese MedicineFirst Clinical Medical School, Gansu University of Chinese MedicineChest Clinic Center, Gansu Provincial People’s HospitalAbstract Esophageal cancer is a grave malignant condition. While radiotherapy, often in conjunction with chemotherapy, serves as a cornerstone in the management of locally advanced or metastatic cases, patient tolerance and treatment resistance frequently hinder its efficacy. Cell-in-cell structures, prevalent in various tumors, have been linked to prognosis. Hence, investigating the prognostic significance and regulatory mechanisms of genes related to these intracellular structures in esophageal cancer is imperative. The Cancer Genome Atlas (TCGA) Esophageal Cancer (ESCA) dataset served as the training set for the analysis. Differentially expressed genes (DEGs) in ESCA samples were identified, with those related to intercellular structures designated cell-in-cell-related differential expression genes (CIC-related DEGs). Cox regression analysis was employed to identify prognostic genes, categorizing samples into high- and low-risk groups based on median risk scores. Validation was conducted using the GSE53624 risk model. Established methodologies included morphological mapping, enrichment analysis, immune infiltration analysis, prognostic gene expression validation, molecular docking, and Reverse Transcription Polymerase Chain Reaction (RT-PCR) validation. Thirty-eight intersecting genes were identified between the disease and normal groups in ESCA samples. Stepwise multivariate Cox analysis pinpointed three prognostic genes: androgen receptor (AR), C-X-C motif chemokine ligand 8 (CXCL8), and epidermal growth factor receptor (EGFR). The risk model’s applicability was confirmed in the GSE53624 dataset, revealing eight significantly different immune-related gene sets. Prognostic gene expression validation demonstrated significant differences between the disease and normal groups in both datasets. The proteins corresponding to the three prognostic genes interacted with gefitinib and osimertinib. RT-PCR results corroborated the differential expression of prognostic genes in esophageal cancer tissues. This study identified AR, CXCL8, and EGFR as prognostic genes and demonstrated their molecular interactions with gefitinib and osimertinib, providing a foundation for ESCA diagnosis and treatment.https://doi.org/10.1186/s12885-025-13483-8Esophageal cancerBioinformaticsCell-in-cellMolecular dockingPrognostic risk model
spellingShingle Wei Cao
Dacheng Jin
Weirun Min
Haochi Li
Rong Wang
Jinlong Zhang
Yunjiu Gou
Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
BMC Cancer
Esophageal cancer
Bioinformatics
Cell-in-cell
Molecular docking
Prognostic risk model
title Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
title_full Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
title_fullStr Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
title_full_unstemmed Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
title_short Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms
title_sort prognostic values of intracellular cell related genes in esophageal cancer and their regulatory mechanisms
topic Esophageal cancer
Bioinformatics
Cell-in-cell
Molecular docking
Prognostic risk model
url https://doi.org/10.1186/s12885-025-13483-8
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