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基于转录组学的分泌组分析鉴定的 DSG2 血浆水平升高是喉癌的一个潜在预后生物标志物。

Increased DSG2 plasmatic levels identified by transcriptomic-based secretome analysis is a potential prognostic biomarker in laryngeal carcinoma.

机构信息

Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.

Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.

出版信息

Oral Oncol. 2020 Apr;103:104592. doi: 10.1016/j.oraloncology.2020.104592. Epub 2020 Feb 19.

Abstract

OBJECTIVES

The tumor secretome deconvolution is a promising strategy to identify diagnostic and prognostic biomarkers. Here, transcriptomic-based secretome analysis was performed aiming to discover laryngeal squamous cell carcinomas (LSCC) biomarkers from potentially secreted proteins (PSPs).

MATERIAL AND METHODS

The tumor expression profile (35 LSCC biopsies compared with surrounding normal tissues - SN) revealed 589 overexpressed genes. This gene list was used for secretome analysis based on laryngeal tumors and related secretome databases.

RESULTS

Forty-nine (Laryngeal tumor secretome database) and 50 (Human Protein Atlas and Cancer Secretome Database) PSPs presented an association with worse overall survival. Specifically, DSG2 overexpression was strongly correlated with poor survival and distant metastasis. DSG2 increased expression was confirmed in the LSCC dataset (LSCC = 111; SN = 12) from TCGA. A significant association between shorter survival and DSG2 overexpression was also detected. In an independent cohort of cases, we analyzed and confirmed high protein levels of DSG2 in plasma from LSCC patients.

CONCLUSION

A set of PSPs including the circulating DSG2, were associated with shorter overall survival in LSCC. DSG2 overexpression was also correlated with distant metastasis. The high plasmatic protein levels of DSG2 suggest its potential to be tested in liquid biopsies and applied as prognostic biomarker of LSCC.

摘要

目的

肿瘤分泌组学解析是一种有前途的策略,可以识别诊断和预后生物标志物。在这里,我们进行了基于转录组的分泌组分析,旨在从潜在分泌蛋白 (PSP) 中发现喉鳞状细胞癌 (LSCC) 的生物标志物。

材料与方法

肿瘤表达谱(35 例 LSCC 活检与周围正常组织-SN 比较)显示 589 个过表达基因。该基因列表用于基于喉肿瘤和相关分泌组数据库的分泌组分析。

结果

49 个(喉肿瘤分泌组数据库)和 50 个(人类蛋白质图谱和癌症分泌组数据库)PSP 与总生存期较差相关。具体来说,DSG2 过表达与不良预后和远处转移密切相关。TCGA 的 LSCC 数据集(LSCC=111;SN=12)证实了 DSG2 表达增加。在独立的病例队列中,我们分析并证实了 LSCC 患者血浆中 DSG2 蛋白水平较高。

结论

一组包括循环 DSG2 的 PSP 与 LSCC 的总生存期较短相关。DSG2 过表达也与远处转移相关。DSG2 蛋白的高血浆水平提示其有可能在液体活检中进行测试,并作为 LSCC 的预后生物标志物。

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