Yao Qian, Hou Wei, Chen Junbing, Bai Yanhua, Long Mengping, Huang Xiaozheng, Zhao Chen, Zhou Lixin, Niu Dongfeng
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Front Med (Lausanne). 2022 Jul 28;9:943887. doi: 10.3389/fmed.2022.943887. eCollection 2022.
Adenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC.
We applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information.
A total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity.
This study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.
腺样囊性癌（ACC）是一种罕见的三阴性乳腺癌，具有惰性的临床行为。鉴于其与其他基底样三阴性乳腺癌（BL-TNBC）在形态学、免疫组织化学和分子特征上有大量重叠，准确诊断ACC对于有效的临床治疗至关重要。蛋白质组与临床病理特征的综合分析可能有助于区分这两种肿瘤，并深入了解ACC的生物学行为和潜在的靶向治疗。
我们应用基于质谱的定量蛋白质组学分析了5例ACC和5例BL-TNBC的配对肿瘤及相邻正常乳腺组织中的蛋白质表达。还收集了生物信息学分析以及临床病理特征，包括组织学特征、免疫组织化学和FISH结果，以获取全面信息。
在ACC和BL-TNBC之间共鉴定出307种差异表达蛋白（DEP）。DEP的聚类分析清楚地将ACC与BL-TNBC区分开来。基因集富集分析（GSEA）发现，与BL-TNBC相比，ACC的免疫反应下调，这与ACC的PD-L1阴性表达一致。囊泡介导的转运也受到抑制，而细胞外基质组织在ACC中富集。DEP中上调最明显的蛋白质是整合素β4（ITGB4）、多功能蛋白聚糖（VCAN）和皮肤蛋白（DPT）。此外，与正常乳腺组织相比，ACC显示核糖体生物合成和RNA剪接活性升高。
本研究提供的证据表明，ACC与BL-TNBC相比具有明显不同的蛋白质组学特征，并增进了我们对ACC分子机制和生物学过程的理解，这可能有助于鉴别诊断和抗癌策略。
