性别特异性蛋白质组学分析鉴定妊娠区带蛋白为食管腺癌中补体相关的预后不良标志物
Sex-Specific Proteomic Profiling Identifies Pregnancy Zone Protein as a Complement-Linked Marker of Adverse Prognosis in Esophageal Adenocarcinoma.
作者
作者单位
- Institute of Pathology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
- Department of Internal Medicine I, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
- Department of General, Visceral and Cancer Surgery, Faculty of Medicine, University Hospital of Cologne, Cologne, Germany.
摘要
中文
食管腺癌（EAC）表现出显著的男性优势，男女比例高达8.5:1，然而这种性别差异的分子基础仍未被充分表征。我们使用基于质谱的蛋白质组学分析了92例EAC标本，包括来自未经治疗患者的47例女性和45例男性肿瘤。使用差异表达、通路富集、免疫组织化学和生存分析来鉴定性别相关的蛋白质组学特征和预后标志。蛋白质组学分析揭示了EAC中局灶性但生物学上有意义的性别差异。经过多重检验校正后，三种蛋白质存在差异表达：常染色体蛋白妊娠区带蛋白（PZP）在女性肿瘤中富集，而Y染色体编码蛋白DDX3Y和RPS4Y1在男性肿瘤中过表达。在名义显著性水平上，女性肿瘤中上调的蛋白质显示出免疫相关通路的显著富集。与PZP表达相关的蛋白质形成以补体级联为主的网络。临床上，PZP高表达仅在男性患者中与显著较差的总生存相关，在合并队列或仅女性队列中未检测到显著关联。全蛋白质组生存分析进一步证明了独特的性别特异性预后景观。我们的研究首次全面描述了EAC中性别相关的蛋白质组学差异。性别塑造了免疫相关通路、预后蛋白质组学特征和生存关联。PZP是一种性别差异、补体相关的蛋白质，在男性患者中具有不良预后意义，强调性别是EAC中生物学和临床上相关的变量。
English
Esophageal adenocarcinoma (EAC) exhibits marked male predominance with male-to-female ratios reaching 8.5:1, yet the molecular basis underlying this sex disparity remains poorly characterized. We analyzed 92 EAC specimens using mass spectrometry-based proteomics, comprising 47 female and 45 male tumors from treatment-naïve patients. Differential expression, pathway enrichment, immunohistochemical, and survival analyses were used to identify sex-associated proteomic features and prognostic signatures. Proteomic profiling revealed focal yet biologically meaningful sex differences in EAC. After multiple testing correction, three proteins were differentially expressed: the autosomal protein pregnancy zone protein (PZP), enriched in female tumors, and the Y-chromosome-encoded proteins DDX3Y and RPS4Y1, which were overexpressed in male tumors. At nominal significance, proteins upregulated in female tumors showed marked enrichment of immune-related pathways. Proteins correlated with PZP expression formed a network dominated by complement cascade. Clinically, elevated PZP expression was associated with significantly poorer overall survival specifically in male patients, with no significant association detected in the combined or female-only cohort. Proteome-wide survival analyses further demonstrated distinct sex-specific prognostic landscapes. Our study provides the first comprehensive characterization of sex-associated proteomic differences in EAC. Sex shapes immune-related pathways, prognostic proteomic signatures, and survival associations. PZP emerges as a sex-differential, complement-associated protein with adverse prognostic significance in male patients, highlighting sex as a biologically and clinically relevant variable in EAC.
分类与指标
- 研究类型
- 基础研究
- 病种
- 食管癌
- JCR 分区
- Q2
- 影响因子
- 4.9
- 新锐分区
- 2区