Lymphocyte-specific kinase expression is a prognostic indicator in ovarian cancer and correlates with a prominent B cell transcriptional signature
Lymphocyte-specific kinase expression is a prognostic indicator in ovarian cancer and correlates with a prominent B cell transcriptional signature
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DOI：
10.1007/s00262-019-02385-x
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发表时间：
2019-09-01
影响因子：
5.8
通讯作者：
Jazaeri, Amir
中科院分区：
文献类型：
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作者：
Hinchcliff, Emily;Paquette, Cherie;Jazaeri, Amir
目的探讨免疫相关基因表达对高级别浆液性卵巢癌(HGSOC)预后及生物学意义的影响。方法应用肿瘤基因组图谱(TCGA)对一组免疫相关基因在高级别浆液性卵巢癌(HGSOC)中的表达进行分析。在一组独立的72例HGSOC患者中，LCK的预后价值通过IHC进行了验证。使用RNAseq对多种肿瘤类型的LCK的预后表现与细胞溶解评分(CyT)进行比较。结果LCK高表达样本中LCK mRNA的高表达是卵巢癌患者生存的重要指标。LCK高表达患者的中位无进展生存期(PFS)为29.4个月，高于LCK高表达患者的16.9个月(P=0.003)，中位总生存期(OS)为95.1个月与44.5个月(P=0.001)。在TCGA提供的所有肿瘤类型中，LCK的表达与细胞毒性进行了比较，在细胞毒性不能预测的HGSOC中，LCK的表达是一个重要的预后预测因子。出乎意料的是，LCK高表达还富含多种免疫球蛋白相关的B细胞转录物。结论LCK是卵巢癌较细胞色素T更好的预后因素。在HGSOC中，LCK高表达以免疫球蛋白和B细胞相关基因的高表达为特征，提示肿瘤浸润性T细胞和B细胞之间的协同作用可能与该病更好的生存有关。
Objective To investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC).Methods Gene expression dependent survival analyses for a panel of immune related genes were evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA). Prognostic value of LCK was validated using IHC in an independent set of 72 HGSOC. Prognostic performance of LCK was compared to cytolytic score (CYT) using RNAseq across multiple tumor types. Differentially expressed genes in LCK high samples and gene ontology enrichment were analyzed.Results High pre-treatment LCK mRNA expression was found to be a strong predictor of survival in a set of 535 ovarian cancers. Patients with high LCK mRNA expression had a longer median progression free survival (PFS) of 29.4 months compared to 16.9 months in those without LCK high expression (p=0.003), and longer median overall survival (OS) of 95.1 months versus 44.5 months (p=0.001), which was confirmed in an independent cohort by IHC (p=0.04). LCK expression was compared to CYT across tumor types available in the TCGA and was a significant predictor of prognosis in HGSOC where CYT was not predictive. Unexpectedly, LCK high samples also were enriched in numerous immunoglobulin-related and other B cell transcripts.Conclusions LCK is a better prognostic factor than CYT in ovarian cancer. In HGSOC, LCK high samples were characterized by higher expression of immunoglobulin and B-cell related genes suggesting that a cooperative interaction between tumor infiltrating T and B cells may correlate with better survival in this disease.