识别R0切除后肾上腺皮质癌复发的基因组特征
Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection
影响因子:2.70000
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
摘要
肾上腺皮质癌（ACC）是一种罕见且具有侵略性的恶性肿瘤，治疗方案有限。尽管最近有进步揭示了这些肿瘤的基因组驱动因素，但尚不清楚哪些基因组特征与复发有关，尤其是在R0切除后。肾上腺皮质癌患者在癌症基因组基因组ATLAS中用肾上腺切除术治疗的患者使用CBIOPORTAL鉴定出复发数据。回顾性分析了临床病理变量，基因组学，治疗模式和结果。92例肾上腺皮质癌患者，84例复发数据，有52％的肿瘤复发。年龄和性别之间的年龄和性别群体之间没有显着差异。非急流患者的总生存期明显更长（54个月比35个月，p = .0036）。两组的辅助辐射相似（25.0％vs 16.2％，p = .4164）。囊囊或静脉浸润或中位肿瘤大小没有差异。 62例患者进行了R0切除，重复了40.3％（n = 25/62）。 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）途径与复发显着相关。复发的中位时间为7.9个月；早期复发（<7.9个月）与MYC途径的改变有关（40.9％vs 9.1％，p = .0339）。这项研究确定了PI3K，WNT和细胞周期途径中与肾上腺皮质癌复发相关的基因组特征，包括在R0进行R0的人，包括那些接受R0的人。有必要将这些特征作为决定辅助疗法或有针对性治疗的预后工具的效用。
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.