Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling

Uterine serous carcinoma (USC) represents only a small proportion of all uterine cancer cases, but patients with this aggressive subtype typically have high rates of chemotherapy resistance, disease recurrence, and constitute a disproportionately high percentage of the deaths. Improving the clinical management of USC is predicated by better characterization of the tumor microenvironment (TME) and the molecular features driving disease pathology. To improve our understanding of intratumoral heterogeneity (ITH) within the USC TME, we investigated proteome and transcriptome alterations in spatially resolved laser microdissection (LMD) enriched cellular subpopulations from nine USC patient tumor tissue specimens. LMD enriched samples were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), reverse phase protein microarray (RPPA), and targeted RNA-sequencing (RNA-seq).

子宫浆液性癌（Uterine serous carcinoma, USC）仅占所有子宫恶性肿瘤病例的一小部分，但该侵袭性亚型患者通常化疗耐药率与疾病复发率较高，且在子宫癌相关死亡病例中占比极高。优化子宫浆液性癌的临床诊疗方案，有赖于更精准地解析肿瘤微环境（tumor microenvironment, TME）以及驱动疾病病理进程的分子特征。为加深对子宫浆液性癌肿瘤微环境中肿瘤内异质性（intratumoral heterogeneity, ITH）的认知，本研究针对9例子宫浆液性癌患者肿瘤组织标本中经空间分辨激光显微切割（spatially resolved laser microdissection, LMD）富集的细胞亚群，开展了蛋白质组与转录组变化分析。对经LMD富集的标本，研究采用液相色谱-串联质谱（liquid chromatography-tandem mass spectrometry, LC-MS/MS）、反相蛋白质微阵列（reverse phase protein microarray, RPPA）以及靶向RNA测序（targeted RNA-sequencing, RNA-seq）进行检测分析。