CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.
Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities.
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我们对高级别浆液性卵巢癌（HGSOC）组织标本中纯度跨度较大的 bulk 肿瘤和激光显微切割富集的肿瘤细胞群体进行了深度蛋白质基因组学分析。我们发现无进展生存期较长的患者具有增强的免疫相关特征，并在一个独立的 65 例 HGSOC 患者队列中验证了与TIL（肿瘤浸润淋巴细胞）相关的蛋白，还在另一个 126 例 HGSOC 患者队列中验证了其与总生存期的相关性。我们发现同源重组缺陷（HRD）肿瘤富集与代谢和氧化磷酸化相关的通路，并在独立患者队列中进行了验证。我们进一步发现 polycomb 复合蛋白 BMI-1 在同源重组功能正常（HRP）肿瘤中升高，BMI-1 升高与 HRP 而非 HRD HGSOC 患者较差的总生存期相关，并且 HRP HGSOC 细胞对 BMI-1 抑制具有独特敏感性。
We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity.
We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort.
We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts.
We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.
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