'Spatial Map' of Esophageal Cancer After Chemoradiotherapy Unveiled: "Radioresistance Genes Concentrated at Tumor Edge"

Analysis of Surgical Tissue from 56 Esophageal Cancer Patients
Gene Activity Varies by Tissue Location
"Higher Inflammation-Related Gene Activity Linked to Increased Risk of Progression, Recurrence, and Death"

When examining cancer tissue from esophageal cancer patients who received chemoradiotherapy, researchers found that genetic activity differed depending on the location within the same tissue. In particular, gene groups associated with resistance to radiation were most active at the edge of the tumor tissue.

Seoul National University Hospital announced on October 1, 2026, that a joint research team consisting of Professor Beomseop Jang and Professor Hakjae Kim from the Department of Radiation Oncology, Professor Kwonjoong Na from the Department of Cardiovascular and Thoracic Surgery, Professor Hyesung Lee from the Department of Pathology, and former Professor Byunghyuk Kim from the Department of Radiation Oncology at Seoul Metropolitan Boramae Hospital, analyzed surgical tissue from 56 patients with esophageal squamous cell carcinoma who underwent preoperative chemoradiotherapy and esophagectomy between 2005 and 2022.

From the left, Professor Beomseop Jang and Professor Hakjae Kim of the Department of Radiation Oncology at Seoul National University Hospital, Professor Kwonjung Na of the Department of Cardiovascular and Thoracic Surgery, and Professor Hyesung Lee of the Department of Pathology. Seoul National University Hospital

The research team used spatial transcriptomics, a technique to measure gene activity while retaining positional information within tissue. Using this approach, they divided the residual esophageal cancer tissue following treatment into eight regions based on their location and characteristics.

Among these, five key regions were identified in at least 10 patients: the tumor edge, fibrous-immune region, stromal boundary, mucosal transition zone, and stress response region. The 'fibrous-immune region' accounted for an average of 53.0% of the patient tissue, making it the largest.

When the team compared the activity of 37 gene groups in the key regions, all gene groups displayed location-dependent differences. Notably, the ΔNp63/NRF2 gene group—known to be associated with radioresistance—was most active at the 'tumor edge' and least active at the 'stromal boundary.'

The researchers then investigated whether these differences were also related to patient outcomes. Among patients with residual cancer after chemoradiotherapy whose prognosis could not be accurately predicted based only on conventional pathological exams (classified as grade 1 or 2), the team analyzed 29 cases. Of these, 27 had a detectable 'fibrous-immune region' and were included in the study.

The analysis revealed that the higher the gene activity related to inflammation in the 'fibrous-immune region,' the greater the risk of cancer progression, recurrence, or death. For each standard deviation increase in the gene group score, the risk of progression, recurrence, or death was 1.76 to 2.53 times higher, with the strongest correlation (2.53 times) found in inflammation-related gene groups.

Similar trends were observed in the analysis of all patients. Among the 52 patients in whom the 'fibrous-immune region' could be identified, higher activity of SPP1 and ΔNp63/NRF2 gene groups was associated with shorter overall survival, event-free survival, and periods without local recurrence or distant metastasis. The risk was 1.36 to 1.62 times higher.

However, the research team cautioned that because this study was an exploratory investigation of tissue samples after chemoradiotherapy, further research is needed to determine if these gene groups can accurately predict clinical outcomes.

Professor Beomseop Jang stated, "This study revealed that molecular characteristics of esophageal cancer tissue after chemoradiotherapy differ depending on the location within the tumor. Understanding the tumor microenvironment following esophageal cancer treatment will serve as a foundation for future precision medicine research." The results were published online in the latest edition of the international journal npj Precision Oncology.

This content was produced with the assistance of AI translation services.