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维生素 D 受体在乳腺癌中的预后作用:系统评价和荟萃分析。

Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis.

机构信息

Department of Medical Oncology, The Second People's Hospital of Lianyungang, 41 Hailian Road, Lianyungang, 222000, China.

Department of Radiotherapy, The First People's Hospital of Yancheng, 66 Renmin Street, Yancheng, 224005, China.

出版信息

BMC Cancer. 2020 Nov 1;20(1):1051. doi: 10.1186/s12885-020-07559-w.

DOI:10.1186/s12885-020-07559-w
PMID:33131491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7603743/
Abstract

BACKGROUND

A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis.

METHODS

Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients' survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity.

RESULTS

Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients' overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18-0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than 'immunoreactive score (IRS)>5' and 'IRS > 25', high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30-0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509).

CONCLUSIONS

The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.

摘要

背景

较高的维生素 D 摄入量可改善早期乳腺癌(BC)患者的预后。我们假设维生素 D 的摄入量应与维生素 D 受体(VDR)的表达有关。为了验证这一假设,我们首先打算通过荟萃分析评估 VDR 表达与 BC 患者预后之间的相关性。

方法

检索 PubMed、Embase 和 Cochrane Library(截至 2020 年 5 月 20 日最后更新)中的文献,以寻找评估 VDR 在 BC 中预后作用的研究。提取患者生存的风险比(HRs)进行汇总分析。进行亚组分析、敏感性分析和荟萃回归分析,以探讨异质性的来源。

结果

纳入了 7 篇文献,共 8 项研究,包含 2503 例患者。汇总分析结果显示,VDR 表达通常与 BC 患者的总生存期(OS)、无病生存期(DFS)、癌症特异性生存期(CSS)和无进展生存期(PFS)无相关性(P>0.05)。由于只有探讨 VDR 表达与 OS 之间关系的研究数量大于 5 且存在异质性,我们探讨了这些研究的异质性来源。亚组分析显示,VDR 在核内的表达与 OS 无关,但核和细胞质内的总 VDR 表达较高与 OS 较好有关(合并 HR=0.41;95%CI=0.18-0.95;P=0.038)。此外,在使用“免疫反应评分(IRS)>5”和“IRS>25”以外的截断值的亚组研究中,高 VDR 表达与 OS 较好相关(合并 HR=0.47;95%CI=0.30-0.74;P=0.001)。敏感性分析表明,单个研究结果模式未受到明显影响。荟萃回归表明,异质性的来源不是国家(P=0.657)、病理类型(P=0.614)、分子类型(P=0.423)、染色位置(P=0.481)或截断值(P=0.509)。

结论

通过免疫组织化学评估整个 BC 细胞中的 VDR 蛋白表达水平与 BC 患者的 OS 相关。预计可以根据 VDR 表达为 BC 患者推荐更个性化的维生素 D 摄入和更准确的预后评估。当然,还需要更多的临床前和临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/d308e0b2c17c/12885_2020_7559_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/3507d166185d/12885_2020_7559_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/2413c8cce4d9/12885_2020_7559_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/d308e0b2c17c/12885_2020_7559_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/3507d166185d/12885_2020_7559_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/f21faeaacf65/12885_2020_7559_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/e706ccf68cef/12885_2020_7559_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/5ea40cb07aa5/12885_2020_7559_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/fd34ec3e686e/12885_2020_7559_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/2413c8cce4d9/12885_2020_7559_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/7603743/d308e0b2c17c/12885_2020_7559_Fig7_HTML.jpg

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