Related Experiment Video
Updated: Sep 14, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
The AP-1 factor JUNB correlates with poor survival of patients with esophageal adenocarcinoma
Nikolai Schleussner1, Karl Knipper2, Ella Leugner3
1Department of General, Visceral, Thorax and Transplantation Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. nikolai.schleussner@uk-koeln.de.
Abstract:
Malignant cells have in contrast to non-transformed cells de-regulated transcriptional networks. The activator protein-1 (AP-1) transcription factor complex is expressed in many cancer entities including adenocarcinomas and has been correlated to de-regulated transcription and tumor-promoting mechanisms. Despite complex treatment approaches, esophageal cancer is still associated with poor overall survival. There is an urgent need for better patient stratification to increase the outcome of the multimodal treatment. This study investigated the expression of two AP-1 factors, cJUN and JUNB, and their role in 735 patients with esophageal cancer undergoing surgery. We performed immunohistochemical stainings for cJUN and JUNB and correlated the expression to the clinical outcome. Patients with a high JUNB expression level correlate to a reduced overall survival (OS) compared to patients with a low expression. Furthermore, in the multivariate analysis high JUNB expression was shown to be an independent risk factor for reduced patient survival. In addition, subgroup analysis demonstrated a significantly reduced OS for high JUNB expression in the subgroup of patients with neoadjuvant treatment. Strikingly, tumors co-expressing cJUN and JUNB were associated with poorer overall survival compared to those expressing only one or neither of the transcriptions factors. Our study suggests JUN expression as a novel biomarker to stratify patients, especially in the subgroup of neoadjuvant treated patients. Our findings have translational implications as targeting JUN might complement current available multimodal treatment approaches.
Insights
High JUNB expression in esophageal cancer patients correlates with reduced survival. Co-expression of cJUN and JUNB further worsens outcomes, suggesting JUN factors as potential biomarkers for patient stratification.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant cells exhibit deregulated transcriptional networks compared to non-transformed cells.
- The activator protein-1 (AP-1) transcription factor complex, including cJUN and JUNB, is implicated in cancer progression and tumor promotion.
- Esophageal cancer presents a significant survival challenge despite multimodal treatments, highlighting the need for improved patient stratification.
Purpose of the Study:
- To investigate the expression of cJUN and JUNB in esophageal cancer.
- To evaluate the correlation between cJUN and JUNB expression and patient survival outcomes.
- To determine the potential of JUN factors as biomarkers for patient stratification in esophageal cancer.
Main Methods:
- Immunohistochemical staining was performed to assess cJUN and JUNB expression levels.
- Expression data were correlated with clinical outcomes in a cohort of 735 esophageal cancer patients.
- Multivariate and subgroup analyses were conducted to identify independent prognostic factors.
Main Results:
- High JUNB expression was significantly associated with reduced overall survival (OS) in esophageal cancer patients.
- High JUNB expression emerged as an independent risk factor for decreased patient survival.
- Tumors co-expressing cJUN and JUNB showed poorer OS compared to those with single or no expression of these factors.
- A significantly reduced OS was observed in patients with high JUNB expression within the neoadjuvant treatment subgroup.
Conclusions:
- JUNB expression serves as a potential prognostic biomarker for esophageal cancer.
- Co-expression of cJUN and JUNB indicates a poorer prognosis.
- JUN factors may aid in stratifying patients, particularly those receiving neoadjuvant therapy.
- Targeting JUN pathways could offer complementary therapeutic strategies for esophageal cancer.
Related Concept Videos
01:21Cancer Survival Analysis
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...