Comparative genomic analysis of tumor tissue and surgical margin distances in esophageal squamous cell carcinoma.

e15064 Background: Surgical resection is crucial for managing esophageal squamous cell carcinoma (ESCC), with emerging evidence indicating that resection distances may affect prognosis. However, the genetic relationship between tumors and adjacent tissues, particularly regarding the similarity of tumor tissues with varying margin distances, remains poorly understood. Methods: This prospective study enrolled 23 patients undergoing surgical resection for ESCC, with margins standardized at 2 cm (M2), 4 cm (M4), and 6 cm (M6). Tumor and adjacent tissues were collected for mutational profiling via next-generation sequencing (NGS). Shared genetic alterations were identified and the Jaccard index was used to evaluate similarities across different tissue types. Results: The median age of the study cohort was 61 years (range: 55-67), with 78.3% of the patients exhibiting high to moderate tumor differentiation. Tumor samples were available from all 23 patients, along with 18 adjacent tissues from M2, 17 from M4, and 21 from M6. A significant reduction in shared alterations was observed with increasing distance from the tumor ( p < 0.0001), demonstrating a strong negative correlation ( r = -0.73, p < 0.05). Specifically, the number of shared variants declined from 0 to 4 cm, followed by a slight increase from 4 to 6 cm. The Jaccard index confirmed that the M4 exhibited the lowest genetic similarity to tumors ( p < 0.05), with a negative correlation also noted between the Jaccard index and distance ( r = -0.73, p < 0.05). Similarly, a trend towards increased correlation was observed between the Jaccard index and the M6-Tumor compared to the M4-Tumor. Conclusions: Our findings elucidate the genetic heterogeneity between tumors and adjacent margins. The 4 cm resection margin exhibited the lowest genetic similarity to tumor samples, signifying a crucial threshold that may influence tumor recurrence and patient prognosis.