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NCALD 低表达与上皮性卵巢癌的化疗耐药和不良预后相关。

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer.

机构信息

Department of Gynecologic oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning, Guangxi, 530021, P.R. China.

出版信息

J Ovarian Res. 2020 Mar 30;13(1):35. doi: 10.1186/s13048-020-00635-6.

Abstract

BACKGROUND

Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis.

METHODS

High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter.

RESULTS

In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-β signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS.

CONCLUSIONS

NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.

摘要

背景

卵巢癌患者外周血中 NCALD(神经钙调蛋白 delta)表达水平低预示着预后不良。然而,NCALD 在卵巢癌中的分子机制及其与化疗结果的关系尚不清楚。本研究旨在探讨 NCALD 的潜在信号通路,并评估其预测化疗结果和预后的能力。

方法

从 TCGA 下载高通量 RNA 测序数据。GSEA 探索 NCALD 的潜在信号通路。通过 TCGA 数据和临床样本检测化疗敏感和化疗耐药卵巢癌患者中 NCALD 的表达。ROC 分析证实了 NCALD 预测化疗结果的能力。使用 Kaplan-Meier plotter 评估 NCALD 表达与卵巢癌患者预后的关系。

结果

在 NCALD 过表达的患者中,与 ERK1/2 信号通路、NF-κB 信号通路、TGF-β 信号通路和免疫反应通路相关的基因表达增加,尤其是 ERK1/2 信号通路。耐药患者中 NCALD 的表达明显低于敏感患者。在 TCGA 数据和免疫组化样本中,NCALD 表达预测化疗结果的 AUC 分别为 0.59 和 0.64。在临床样本中,NCALD 低表达与 OS 和 PFS 不良相关。

结论

NCALD 可能在卵巢癌中激活 ERK1/2 信号通路。作为化疗敏感性的新生物标志物,NCALD 在化疗耐药卵巢癌患者中显著下调。卵巢癌中 NCALD 的低表达与 OS 和 PFS 不良相关。未来需要进一步研究 NCALD 在卵巢癌中的潜在机制和临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fcc/7106630/3bd9b776293f/13048_2020_635_Fig1_HTML.jpg

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