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乳腺癌患者血清唾液酸化路易斯 X(sLe)水平和炎症介质升高。

Elevated serum levels of sialyl Lewis X (sLe) and inflammatory mediators in patients with breast cancer.

机构信息

Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX, 77030, USA.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

出版信息

Breast Cancer Res Treat. 2019 Aug;176(3):545-556. doi: 10.1007/s10549-019-05258-0. Epub 2019 May 3.

Abstract

PURPOSE

The carbohydrate sialyl Lewis (sLe) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLe and inflammatory cytokines/chemokines in breast cancer sera.

METHODS

We retrospectively measured sLe and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLe and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLe using a cut-off of 8 U/mL as previously defined.

RESULTS

Median serum sLe was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLe > 8 U/mL have a significantly shorter progression-free survival (PFS) (P = 0.0074) and overall survival (OS (P = 0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P = 0.001 and P < 0.001, respectively) and PFS (P = 0.010 and P < 0.001, respectively). sLe, MCP-1 and IP-10 remained significant in multivariate survival analysis.

CONCLUSION

Elevated serum sLe was associated with invasive cancer but not DCIS. High serum sLe levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLe may have prognostic value in breast cancer.

摘要

目的

碳水化合物唾液酸化路易斯(sLe)介导细胞黏附,在免疫细胞的正常功能中至关重要,并且经常在癌细胞上过度表达。我们评估了乳腺癌血清中 sLe 与炎症细胞因子/趋化因子的相关性、差异水平和预后价值。

方法

我们回顾性测量了 26 例非浸润性导管原位癌(DCIS)、154 例非转移性浸润性乳腺癌(非 MBC)、63 例转移性乳腺癌(MBC)患者和 43 例健康对照者的血清 sLe 和一组细胞因子/趋化因子。使用非参数检验评估患者组和健康对照组之间 sLe 和炎症细胞因子的差异,并使用先前定义的 8 U/mL 作为截断值,对 sLe 的预后潜力进行生存分析。

结果

与健康对照组相比,浸润性乳腺癌患者(MBC 和非 MBC)的血清 sLe 中位数明显升高,但 DCIS 患者则不然。在单变量分析中,我们证实血清 sLe>8 U/mL 的患者无进展生存期(PFS)(P=0.0074)和总生存期(OS)(P=0.0003)显著缩短。同样,血清 MCP-1 和 IP-10 水平较高的患者 OS(P=0.001 和 P<0.001)和 PFS(P=0.010 和 P<0.001)均较短。在多变量生存分析中,sLe、MCP-1 和 IP-10 仍然具有统计学意义。

结论

血清 sLe 升高与浸润性癌症相关,但与 DCIS 无关。高水平的血清 sLe 与炎症介质相关,可能在促进乳腺癌肿瘤的局部侵袭中发挥作用。此外,血清 MCP-1、IP-10 和 sLe 可能具有乳腺癌的预后价值。

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