采用生物信息学分析方法研究分泌白细胞蛋白酶抑制剂（SLPI）在乳腺癌中的表达及临床意义。
The expression and clinical significance of secretory leukocyte proteinase inhibitor (SLPI) in mammary carcinoma using bioinformatics analysis.
机构信息
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Medical College Anhui University of Science and Technology, Huainan 232001, China.
出版信息
Gene. 2019 Dec 15;720:144088. doi: 10.1016/j.gene.2019.144088. Epub 2019 Aug 30.
BACKGROUND
Secretory leukocyte protease inhibitor (SPLI) was a secreted protein which belongs to a member of whey acidic protein four-disulfide core family. In breast cancer (BC) it may inhibit cell proliferation and promote cancer metastasis. In this study, a comprehensive bioinformatics analysis was performed to identify the expression and prognostic value of SLPI in breast cancer.
METHODS
SLPI expression in breast cancer was analyzed in Oncomine online database, which was subsequently confirmed by quantitative PCR (qPCR) in 18 BC samples and western blotting in 26 BC samples. Breast cancer gene-expression miner v4.1 was used to access the expression level with clinicopathological parameters in breast cancer patients. The prognostic values of SLPI in breast cancer were evaluated using the PrognoScan database.
RESULTS
Our results indicated that SLPI was downregulated in breast cancer than in normal tissues. SLPI expression was found to be negatively correlated with estrogen receptor (ER) and progesterone receptor (PR) status. SLPI expression level was decreased in negative basal-like status patients compared with positive basal-like status. Meanwhile, triple-negative breast cancer status positive correlated with SLPI. We confirmed a positive correlation between SLPI and interleukin 17 receptor B (IL17RB) express in breast cancer tissues via oncomine co-expression analysis. Ten proteins: Elastase, Granulin, Lipocalin, Defensin beta 103B, Defensin beta 103A, Tubulin, Heparin-binding EGF-like growth factor, Interleukin 6, Epidermal growth factor, Phospholipid scramblase 1 were determinate interactions with SLPI by STRING.
CONCLUSION
SLPI could as a biomarker to predict the prognosis values of breast cancer. However, further comprehensive study and mining more evidence are needed to clarify our results.
背景
分泌白细胞蛋白酶抑制剂（SPLI）是一种分泌蛋白，属于乳白蛋白四硫键核心家族成员。在乳腺癌（BC）中，它可能抑制细胞增殖并促进癌症转移。在这项研究中，进行了全面的生物信息学分析，以确定 SPLI 在乳腺癌中的表达和预后价值。
方法
在 Oncomine 在线数据库中分析乳腺癌中 SPLI 的表达，随后通过 18 例 BC 样本的定量 PCR（qPCR）和 26 例 BC 样本的 Western blot 进行验证。使用 Breast Cancer Gene-Expression Miner v4.1 访问乳腺癌患者的临床病理参数的表达水平。使用 PrognoScan 数据库评估 SPLI 在乳腺癌中的预后价值。
结果
我们的结果表明，SPLI 在乳腺癌中的表达低于正常组织。发现 SPLI 的表达与雌激素受体（ER）和孕激素受体（PR）状态呈负相关。与阳性基底样状态相比，阴性基底样状态患者的 SPLI 表达水平降低。同时，三阴性乳腺癌状态与 SPLI 呈正相关。我们通过 Oncomine 共表达分析证实了 SPLI 与乳腺癌组织中白细胞介素 17 受体 B（IL17RB）表达之间的正相关关系。通过 STRING 确定了与 SPLI 相互作用的 10 种蛋白质：弹性蛋白酶、颗粒蛋白、脂联素、防御素β 103B、防御素β 103A、微管蛋白、肝素结合表皮生长因子样生长因子、白细胞介素 6、表皮生长因子、磷脂酶 scramblase 1。
结论
SPLI 可作为预测乳腺癌预后值的生物标志物。然而，需要进一步进行全面的研究和挖掘更多证据来阐明我们的结果。
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