鉴定肾上腺皮质癌（ACC）复发的基因组特征，尤其是在R0切除后

Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection

SURGERY

影响因子:2.7

分区:医学2区 / 外科2区

发表日期:2025 Feb

作者: Benjamin C Greenspun, Dawn Chirko, Rajbir Toor, Kyle Wierzbicki, Teagan E Marshall, Abhinay Tumati, Rasa Zarnegar, Thomas J Fahey, Brendan M Finnerty

DOI: 10.1016/j.surg.2024.09.036

摘要

肾上腺皮质癌（ACC）是一种罕见且具有高度侵袭性的恶性肿瘤，治疗选择有限。尽管近年来对这些肿瘤的基因驱动因素有所揭示，但尚不清楚哪些基因组特征与复发相关，尤其是在R0切除后。通过cBioPortal在Cancer Genome Atlas中识别接受肾上腺切除术且具有复发数据的ACC患者。对其临床病理变量、基因组信息、治疗模式及预后进行回顾性分析。在92例ACC患者中，84例具有复发数据，52%发生了肿瘤复发。年龄和性别在复发组与非复发组间无显著差异。非复发患者的总生存期显著更长（54个月对比35个月，P=0.0036）。辅助放疗在两组中的应用比例相似（25.0%对16.2%，P=0.4164）。在包膜侵犯或静脉侵犯及肿瘤最大径方面未观察到差异。62例患者实现R0切除，且有40.3%（25/62）发生复发。多变量逻辑回归分析控制血管侵犯、静脉侵犯和包膜侵犯后发现，WNT（比值比4.43 [1.09-18.0], P=0.034）、PI3K（比值比7.80 [1.33-45.65], P=0.023）及细胞周期（比值比6.81 [1.43-32.30], P=0.016）路径显著与复发相关。中位复发时间为7.9个月；早期复发（<7.9个月）与MYC通路的变化相关（40.9%对比9.1%，P=0.0339）。本研究鉴定出PI3K、WNT及细胞周期路径的基因组特征，提示其与ACC复发相关，包括在R0切除患者中。未来应探索这些特征作为预后工具，以指导辅助治疗或靶向治疗的潜在应用。

Abstract

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited treatment options. Although there have been recent advancements revealing genomic drivers of these tumors, it remains unclear which genomic signatures are associated with recurrence, particularly following R0 resection.Adrenocortical carcinoma patients treated with adrenalectomy in the Cancer Genome Atlas with recurrence data were identified using cBioPortal. Clinicopathologic variables, genomics, treatment patterns, and outcomes were retrospectively analyzed.Among 92 adrenocortical carcinoma patients, 84 had recurrence data, with 52% experiencing tumor recurrence. Age and sex were not significantly different between recurrent and nonrecurrent groups. Nonrecurrent patients had a significantly longer overall survival (54 months vs 35 months, P = .0036). Adjuvant radiation was administered similarly in both groups (25.0% vs 16.2%, P = .4164). There were no differences in capsular or venous invasion or median tumor size. Sixty-two patients had R0 resection and 40.3% (n = 25/62) recurred. Multivariate logistic regression in this cohort, when controlling for vascular invasion, venous invasion, and capsular invasion, revealed that the WNT (odds ratio 4.43 [1.09-18.0], P = .034), PI3K (odds ratio 7.80 [1.33-45.65], P = .023), and cell cycle (odds ratio 6.81 [1.43-32.30], P = .016) pathways were significantly associated with recurrence. Median time to recurrence was 7.9 months; early recurrence (<7.9 months) was associated with MYC pathway alterations (40.9% vs 9.1%, P = .0339).This study identified genomic signatures in the PI3K, WNT, and cell cycle pathways associated with adrenocortical carcinoma recurrence, including in those who underwent R0 resection. Investigations regarding the utility of these signatures as a prognostic tool to dictate adjuvant therapies or targeted treatment are warranted.