该研究的目的是对具有不同预后的粘膜下穿透性 (Pen) 早期胃癌 (EGC) 的基因改变、微卫星不稳定性 (MSI) 和肿瘤突变负荷 (TMB) 进行全面的基因组表征。来自 EGC 患者的样本收集了接受手术并有 10 年随访数据的患者。使用 Trusight Oncology panel (TSO500) 对组织基因组改变进行表征。对当前病例系列和 TCGA 队列中的 EGC 计算了选定的 218 条 GC 相关通路的通路不稳定性 (PI) 评分。年龄较大和肿瘤位于中上道与复发风险增加显着相关或任何原因导致的死亡（p = 0.006 和 p = 0.032）。即使没有达到统计学显着性，Pen A 肿瘤也更频繁地表现出更高的 TMB 值、更高的 MSI 亚型频率和 PI 评分的总体增加，以及免疫途径的丰富。 ARID1A 基因在 Pen A 肿瘤 (p = 0.006) 以及高 TMB 患者 (p = 0.027) 中突变频率显着更高。含有 LRP1B 改变的肿瘤似乎具有更高的复发或任何原因死亡的风险 (p = 0.089)，主要在复发患者中发生突变 (p = 0.093)。我们发现最具侵袭性的 Pen A 亚型的特点是频率较高ARID1A 突变和更高的遗传不稳定性，而 LRP1B 改变似乎与较低的无病生存率有关。需要进一步研究来提供使用这些标志物对 EGC 患者预后进行分层的基本原理。© 2024。作者。

The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses.Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort.Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093).We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.© 2024. The Author(s).