■透明带糖蛋白3(ZP3)在健康组织中的表达仅限于卵巢卵泡卵母细胞周围的细胞外透明带层和生精谱系的特定细胞。已在各种类型的癌症中观察到ZP3的异位表达,使其成为可能的治疗目标。
■为了支持其作为治疗靶标的有效性,我们通过使用肿瘤活检的免疫组织化学(IHC)研究ZP3表达来扩展癌症相关数据。我们对癌细胞系(CCL)以及肿瘤和正常组织的公开RNA测序(RNA-seq)数据进行了ZP3转录本特异性分析,并通过独立的计算分析和实时定量PCR(qPCR)验证表达数据。还研究了ZP3表达水平与病理和临床参数之间的相关性。
■几种癌症类型的IHC数据显示出丰富的ZP3蛋白染色,局限于细胞质,与卵母细胞中的细胞外蛋白定位相矛盾。我们注意到另一种ZP3RNA转录本,我们称之为“ZP3-癌症”,在缺乏编码控制进入分泌途径的N末端信号肽的遗传信息的基因数据库中进行了注释。这解释ZP3在肿瘤细胞中的胞内定位。分析1339个癌细胞系(CCL)的公开RNA-seq数据,10386个肿瘤组织(癌症基因组图谱)和7481个健康组织(基因型-组织表达)表明ZP3-癌症是肿瘤细胞中占主导地位的ZP3RNA转录物,并且在许多癌症类型中高度富集。特别是在直肠,卵巢,结直肠,前列腺,肺癌和乳腺癌。通过qPCR确认肿瘤细胞中ZP3-癌的表达。更高水平的ZP3-癌症转录物与更具侵袭性的肿瘤和患有各种类型癌症的患者的更差的存活率相关。
■ZP3-Cancer的癌症限制性表达使其成为开发治疗性癌症疫苗的有吸引力的肿瘤抗原,特别是使用mRNA表达技术。
UNASSIGNED: Expression of Zona Pellucida glycoprotein 3 (
ZP3) in healthy tissue is restricted to the extracellular Zona Pellucida layer surrounding oocytes of ovarian follicles and to specific cells of the spermatogenic lineage. Ectopic expression of ZP3 has been observed in various types of cancer, rendering it a possible therapeutic target.
UNASSIGNED: To support its validity as therapeutic target, we extended the cancer related data by investigating
ZP3 expression using immunohistochemistry (IHC) of tumor biopsies. We performed a ZP3 transcript specific analysis of publicly available RNA-sequencing (RNA-seq) data of cancer cell lines (CCLs) and tumor and normal tissues, and validated expression data by independent computational analysis and real-time quantitative PCR (qPCR). A correlation between the ZP3 expression level and pathological and clinical parameters was also investigated.
UNASSIGNED: IHC data for several cancer types showed abundant ZP3 protein staining, which was confined to the cytoplasm, contradicting the extracellular protein localization in oocytes. We noticed that an alternative
ZP3 RNA transcript, which we term \'
ZP3-Cancer\', was annotated in gene databases that lacks the genetic information encoding the N-terminal signal peptide that governs entry into the secretory pathway. This explains the intracellular localization of
ZP3 in tumor cells. Analysis of publicly available RNA-seq data of 1339 cancer cell lines (CCLs), 10386 tumor tissues (The Cancer Genome Atlas) and 7481 healthy tissues (Genotype-Tissue Expression) indicated that ZP3-Cancer is the dominant ZP3 RNA transcript in tumor cells and is highly enriched in many cancer types, particularly in rectal, ovarian, colorectal, prostate, lung and breast cancer. Expression of
ZP3-Cancer in tumor cells was confirmed by qPCR. Higher levels of the ZP3-Cancer transcript were associated with more aggressive tumors and worse survival of patients with various types of cancer.
UNASSIGNED: The cancer-restricted expression of ZP3-Cancer renders it an attractive tumor antigen for the development of a therapeutic cancer vaccine, particularly using mRNA expression technologies.