Functional profiles of curatively treated adenoid cystic carcinoma unveil prognostic features and potentially targetable pathways.

Adenoid cystic carcinoma (ACC) of salivary gland is an indolent tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments. Through a gene expression microarray-based approach followed by GSE functional analysis the expression profile of 46 primary untreated ACC samples and of ACC(h-TERT) tumor cells was analyzed. Patients who experienced early relapse showed enrichment in proliferation-related gene sets, including the G2-M checkpoint, E2F and myc targets, and in gene sets related to IFN signaling and aberrant proteostasis (FDR < 0.1), indicating increased mitotic and transcriptional activity in aggressive ACC. Similar functions were enriched in ACC samples classified by immunohistochemical staining as p63-negative, which exhibited increased protein burden and activation of pro-survival stress response pathways compared to p63-positive tumors. Compared to ACC tissues, ACC(h-TERT) cells share transcriptional features of aggressive p63-negative tumors. These data suggest association of specific pathway alterations with histopathological features of ACC, as recapitulated by p63 testing in patient prognostic stratification, anticipating new avenues for therapeutic intervention. Expression profiling by micorarray. A total of 46 ACC tissue samples were used. RNA was purified from FFPE sections and used for microarray experiments on Affymetrix platform.

涎腺腺样囊性癌（Adenoid cystic carcinoma, ACC）是一种惰性肿瘤，具有延迟复发的倾向，患者生存率较低。针对这种缺乏新型治疗手段的罕见疾病，识别预后不良患者有助于制定基于分子特征的靶向治疗策略。
本研究采用基于基因表达微阵列的实验方法，并结合GSE功能分析，对46例原发性未治疗的ACC样本以及ACC(h-TERT)肿瘤细胞的表达谱进行了分析。出现早期复发的患者，其肿瘤组织在增殖相关基因集（包括G2-M检验点、E2F及myc靶基因）以及IFN信号通路与异常蛋白稳态相关的基因集中存在富集（错误发现率 (False Discovery Rate, FDR) < 0.1），提示侵袭性ACC中存在增强的有丝分裂与转录活性。
通过免疫组化染色被分类为p63阴性的ACC样本，同样富集到了相似的功能通路；与p63阳性肿瘤相比，这类样本表现出更高的蛋白负荷以及促存活应激反应通路的激活。
相较于实体ACC组织样本，ACC(h-TERT)细胞具备侵袭性p63阴性肿瘤的转录组特征。
上述数据表明，特定通路异常与ACC的组织病理学特征存在关联，这一关联可通过患者预后分层中的p63检测得以体现，为治疗干预开辟了新的方向。
本研究通过微阵列技术开展表达谱分析，共纳入46例ACC组织样本。研究人员从福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）切片中提取并纯化RNA，在Affymetrix平台上完成微阵列实验。