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丝氨酸蛋白酶抑制剂 B5 是一种预后生物标志物,可促进肺腺癌的增殖、转移和上皮间质转化(EMT)。

SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma.

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Thorac Cancer. 2023 Aug;14(23):2275-2287. doi: 10.1111/1759-7714.15013. Epub 2023 Jul 9.

Abstract

BACKGROUND

Serine protease inhibitors clade B serpins (SERPINBs) are the largest subclass of protease inhibitors, once thought of as a tumor suppressor gene family. However, some SERPINBs exhibit functions unrelated to the inhibition of catalytic activity.

METHODS

The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Set Cancer Analysis (GSCA), and cBioPortal databases were utilized to investigate SERPINBs expression, prognostic correlation, and genomic variation in 33 cancer types. We also conducted a comprehensive transcriptome analysis in multiple lung adenocarcinoma (LUAD) cohorts to reveal the molecular mechanism of SERPINB5 in LUAD. Then, qPCR and immunohistochemistry were used to verify the expression and prognostic value of SERPINB5 in LUAD patients. Furthermore, knockdown and overexpression of SERPINB5 in LUAD cell lines were performed to evaluate cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).

RESULTS

The expression of SERPINB5 was upregulated and demethylated in LUAD, and its abnormally high expression was significantly correlated with poor overall survival (OS). In addition, the expression of SERPINB5 was analyzed to determine its prognostic value in LUAD and confirmed that SERPINB5 was an independent predictor of LUAD in TCGA and GEO cohorts and qPCR validation with 106 clinical samples. At last, A knockdown of SERPINB5 in LUAD cells reduced proliferation, migration, and EMT. Proliferation, migration, and invasion are promoted by the overexpression of SERPINB5.

CONCLUSION

Therefore, SERPINB5 has shown potential as a prognostic biomarker for LUAD, and it may become a potential therapeutic target for lung adenocarcinoma.

摘要

背景

丝氨酸蛋白酶抑制剂 B 类丝氨酸蛋白酶抑制剂(SERPINBs)是最大的蛋白酶抑制剂亚科,曾被认为是肿瘤抑制基因家族。然而,一些 SERPINBs 表现出与抑制催化活性无关的功能。

方法

利用癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)、基因集癌症分析(GSCA)和 cBioPortal 数据库,研究了 33 种癌症中 SERPINBs 的表达、预后相关性和基因组变异。我们还对多个肺腺癌(LUAD)队列进行了全面的转录组分析,以揭示 SERPINB5 在 LUAD 中的分子机制。然后,使用 qPCR 和免疫组织化学验证了 SERPINB5 在 LUAD 患者中的表达和预后价值。此外,在 LUAD 细胞系中敲低和过表达 SERPINB5 ,以评估细胞增殖、迁移、侵袭和上皮-间充质转化(EMT)。

结果

SERPINB5 在 LUAD 中表达上调且去甲基化,其异常高表达与总生存期(OS)显著相关。此外,分析 SERPINB5 的表达以确定其在 LUAD 中的预后价值,并在 TCGA 和 GEO 队列中通过 qPCR 验证和 106 个临床样本进行了验证,证实 SERPINB5 是 LUAD 的独立预测因子。最后,在 LUAD 细胞中敲低 SERPINB5 可降低增殖、迁移和 EMT。SERPINB5 的过表达可促进增殖、迁移和侵袭。

结论

因此,SERPINB5 已显示出作为 LUAD 预后生物标志物的潜力,它可能成为肺腺癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/612e/10423661/1216a5c8f36b/TCA-14-2275-g001.jpg

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