Matrisome gene expression in treatment-naïve and chemotherapy-treated primary tumor and metastatic tissues of high-grade serous ovarian carcinoma. Matrisome gene expression in treatment-naïve and chemotherapy-treated primary tumor and metastatic tissues of high-grade serous ovarian carcinoma

The extracellular matrix (ECM) of tumors differ significantly from that in normal tissues. Biochemical cues from the tumor ECM critically affect intratumoral signaling contributing to tumor malignancy, growth and response to treatment. In this study, we characterized the expression of 1,027 genes encoding core extracellular matrix and associated proteins defined as the matrisome (Naba et al., 2016) in treatment-naïve and chemotherapy-treated high-grade serous ovarian carcinoma (HGSC) using longitudinal patient cohort consisting of 165 samples. The expression profiling was conducted by using 45 primary tumor samples, 93 metastatic omental-peritoneal-mesenteric tissue samples and 27 ascites-derived cancer cell samples from HGSC patients. By comparing the matrisome gene expression between the primary tumor and metastatic tissues pre- and post-chemotherapy, we identified the cancer cell surrounding fibro-inflammatory tumor-microenvironment to be markedly different in primary tumors compared to metastatic tissues and to change in response to chemotherapy, in terms of both the extent and type of the extracellular matrix proteins. Further study on these specific genes may aid finding potential therapeutic ECM gene targets to enhance HGSC patient outcome. Overall design: Transcriptome profiling analyses of tumor matrisome were performed on 165 high-grade serous ovarian carcinoma patient samples including both treatment-naïve and post-chemotherapy tissue and ascites-derived cancer cells. The raw RNA sequencing data that these effective counts are based on have been deposited in the European Genome-phenome Archive under the accession code (EGAD00001006456, under the study EGAS00001004714).

肿瘤细胞外基质（extracellular matrix, ECM）与正常组织中的细胞外基质存在显著差异。肿瘤细胞外基质所携带的生化信号可显著调控肿瘤内信号传导，进而影响肿瘤恶性表型、增殖及治疗应答。
本研究依托包含165例样本的纵向患者队列，对初治及化疗后高级别浆液性卵巢癌（high-grade serous ovarian carcinoma, HGSC）样本中，1027个编码核心细胞外基质及相关蛋白（matrisome，Naba等，2016）的基因表达特征进行了系统解析。本次表达谱分析采用的样本来自HGSC患者，包括45例原发性肿瘤样本、93例网膜-腹膜-肠系膜转移组织样本以及27例腹水来源癌细胞样本。
通过对比化疗前后原发性肿瘤与转移组织的基质组基因表达谱，本研究发现：相较于转移组织，原发性肿瘤周围的纤维炎性肿瘤微环境存在显著差异，且其细胞外基质蛋白的丰度与类型均会随化疗进程发生改变。针对上述特定基因开展后续研究，或可筛选出具有治疗潜力的细胞外基质基因靶点，进而改善HGSC患者的临床结局。

研究整体设计：对165例HGSC患者样本开展肿瘤基质组转录组谱分析，样本涵盖初治及化疗后组织样本与腹水来源癌细胞样本。本研究用于生成有效计数的原始RNA测序数据，已提交至欧洲基因组-表型组档案馆（European Genome-phenome Archive, EGA），登录号为EGAD00001006456，对应研究编号为EGAS00001004714。