Multi-omics analysis unveils a four-gene prognostic signature in esophageal squamous carcinoma and the therapeutic potential of PKP1
- Xiuzhi Zhang 1, Zhi Wang 2, Yutong Zhao 2, Hua Ye 1,3, Tiandong Li 1, Han Wang 1, Guiying Sun 1, Feifei Liang 2, Liping Dai 4, Peng Wang 5,6, Xiaoli Liu 7
- Xiuzhi Zhang 1, Zhi Wang 2, Yutong Zhao 2
- 1College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China.
- 2Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
- 3Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
- 4Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China. lpdai@zzu.edu.cn.
- 5College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China. wangpeng1658@hotmail.com.
- 6Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China. wangpeng1658@hotmail.com.
- 7Laboratory Department, Henan Provincial People's Hospital, Zhengzhou, 450003, China. lxlzts@126.com.
- 0College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China.
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View abstract on PubMed
Summary
This summary is machine-generated.This study developed a four-gene signature (CCND1-PKP1-JUP-ANKRD12) to predict esophageal squamous cell carcinoma (ESCC) patient survival. PKP1 also shows potential for gene therapy in multiple cancers.
Area Of Science
- Oncology
- Genomics
- Molecular Biology
Background
- Esophageal squamous cell carcinoma (ESCC) is a heterogeneous malignancy with poor patient outcomes.
- Accurate patient stratification and prognostic markers are essential for effective treatment strategies.
Purpose Of The Study
- To classify ESCC subtypes using integrated single-cell and bulk RNA sequencing.
- To develop a novel gene signature for predicting ESCC prognosis and guiding treatment decisions.
Main Methods
- Integrated single-cell and bulk RNA sequencing (RNA-seq) for ESCC characterization.
- Non-negative matrix factorization (NMF) for patient stratification into subtypes.
- Cox and LASSO regression analyses to construct a four-gene prognostic risk model (CCND1-PKP1-JUP-ANKRD12).
- Validation using RT-qPCR, proteomics, and multiplex immunohistochemistry (mIHC).
Main Results
- Identified four distinct ESCC subtypes with unique cellular features and prognoses.
- The CCND1-PKP1-JUP-ANKRD12 signature accurately predicted patient survival, independent of clinical factors.
- Gene expression correlated with immunoregulatory genes and anti-cancer drug sensitivities.
- PKP1 expression linked to EGFR levels and gene effect scores across various cancers.
Conclusions
- The CCND1-PKP1-JUP-ANKRD12 signature offers a promising tool for ESCC prognosis and diagnosis.
- PKP1 dysregulation presents potential therapeutic targets for gene therapy in multiple cancers.
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