CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Clinical significance of SPOCK2 expression signature for high-grade serous ovarian cancer patients.
Clinical significance of SPOCK2 expression signature for high-grade serous ovarian cancer patients.
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SPOCK2 是 SPOCK 家族的成员，是一种 424 个氨基酸的蛋白质，可与糖胺聚糖结合形成蛋白聚糖。本研究的目的是探讨 SPOCK2 的表达谱，并评估其在高 grade 浆液性卵巢癌（HGSOC）中的预后潜力及其与免疫浸润的相关性。
使用癌症基因组图谱数据库（TCGA）、基因表达综合数据库（GEO）、临床蛋白质组肿瘤分析联盟（CPTAC）和人类蛋白质图谱（HPA）数据库分析正常组织和肿瘤组织之间 SPOCK2 mRNA 和蛋白质的表达。使用受试者工作特征（ROC）曲线评估 SPOCK2 的诊断性能。进行 Kaplan-Meier 法和 Cox 回归分析以评估 SPOCK2 对生存的影响。使用列线图预测 SPOCK2 对预后的影响。使用 LinkedOmics 寻找相关基因并进行功能富集分析。通过肿瘤-免疫系统相互作用数据库（TISIDB）和 GSVA 包（V1.34.0）确定 SPOCK2 与TIL（肿瘤浸润淋巴细胞）（TILs）之间的关系。
与正常组织相比，SPOCK2 在 HGSOC 组织中在 mRNA（p < 0.001）和蛋白质（p = 0.03）水平上均高表达。曲线下面积（AUC）为 0.894（CI：0.865-0.923）。Kaplan-Meier 分析显示，SPOCK2 mRNA 高表达的 HGSOC 患者的总生存期（OS）比低表达患者更差（HR = 1.45，p = 0.005）。单因素 logistic 回归分析发现，年龄、初始治疗结局、肿瘤状态、肿瘤残留和 SPOCK2 表达水平与 OS 显著相关（p < 0.05）。列线图模型表明 SPOCK2 具有有效的预测性能。KEGG和GO术语分析显示，SPOCK2主要参与调控细胞外基质。免疫浸润分析显示，SPOCK2可能与TILs的丰度相关。
SPOCK2具有评估HGSOC诊断和预后的潜力，并参与调控细胞外基质和免疫细胞浸润。
Background: SPOCK2 is a member of the SPOCK family, a 424-amino acid protein that binds to glycosaminoglycans to form proteoglycans. The purpose of this study was to explore expression profile of SPOCK2, and evaluate prognostic potential and its correlation with immune infiltration in high-grade serous ovarian cancer (HGSOC). Methods: Expression of SPOCK2 mRNA and protein between normal and tumor tissues were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Receiver operating characteristic (ROC) curve was used to evaluate diagnostic performance of SPOCK2. Kaplan-Meier method and Cox regression analysis were conducted to assess the effect of SPOCK2 on survival. Nomogram was used to predict the impact of SPOCK2 on prognosis. LinkedOmics were used to find correlated genes and perform functional enrichment analyses. The relationships between SPOCK2 and tumor infiltrating lymphocytes (TILs) were determined by tumor-immune system interaction database (TISIDB) and GSVA package (V1.
34. 0). Results: SPOCK2 was highly expressed in HGSOC tissue compared to normal tissue at both mRNA ( p < 0. 001) and protein ( p = 0. 03) levels. The area under the curve (AUC) is 0. 894 (CI: 0. 865-0. 923). Kaplan-Meier analysis showed that HGSOC patients with high-level SPOCK2 mRNA expression had a worse overall survival (OS) than those with a low expression (HR = 1. 45, p = 0. 005). Univariate logistic regression analysis found that age, primary therapy outcome, tumor status, tumor residual, and SPOCK2 expression level were significantly associated with OS ( p < 0.
05). The nomogram model indicated an effective predictive performance of SPOCK2. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) term analyses showed that SPOCK2 were mainly involved in regulating extracellular matrix. Immune infiltration analysis showed that SPOCK2 may correlate with abundance of TILs. Conclusion: SPOCK2 has potentials to estimate diagnosis and prognosis for HGSOC and is involved in regulating extracellular matrix and immune cell infiltration.
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