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BCAP31,一种癌症/睾丸抗原样蛋白,可作为非小细胞肺癌转移的探针。

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis.

机构信息

Department of Immunology, the Fourth Military Medical University, No.169 Changle W. Rd., Xi'an, 710032, China.

Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, No.169, Changle W. Rd., Xi'an, 710032, China.

出版信息

Sci Rep. 2020 Mar 4;10(1):4025. doi: 10.1038/s41598-020-60905-7.

Abstract

Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage. Therefore, exploring the mechanisms underlying metastasis is key to understanding the development of NSCLC. The expression of B cell receptor-associated protein 31 (BCAP31), calreticulin, glucose-regulated protein 78, and glucose-regulated protein 94 were analyzed using immunohistochemical staining of 360 NSCLC patients. It resulted that the high-level expression of the four proteins, but particularly BCAP31, predicted inferior overall survival. What's more, BCAP31 was closely associated with histological grade and p53 status, which was verified by seven cohorts of NSCLC transcript microarray datasets. Then, three NSCLC cell lines were transfected to observe behavior changes BCAP31 caused, we found the fluctuation of BCAP31 significantly influenced the migration, invasion of NSCLC cells. To identify the pathway utilized by BCAP31, Gene Set Enrichment Analysis was firstly performed, showing Akt/m-TOR/p70S6K pathway was the significant one, which was verified by immunofluorescence, kinase phosphorylation and cellular behavioral observations. Finally, the data of label-free mass spectroscopy implied that BCAP31 plays a role in a fundamental biological process. This study provides the first demonstration of BCAP31 as a novel prognostic factor related to metastasis and suggests a new therapeutic strategy for NSCLC.

摘要

非小细胞肺癌(NSCLC)代表了大多数肺癌,通常在晚期转移阶段被诊断出来。因此,探索转移的机制是理解 NSCLC 发展的关键。对 360 名 NSCLC 患者进行免疫组织化学染色,分析了 B 细胞受体相关蛋白 31(BCAP31)、钙网蛋白、葡萄糖调节蛋白 78 和葡萄糖调节蛋白 94 的表达。结果表明,四种蛋白的高水平表达,尤其是 BCAP31,预示着总体生存率降低。更重要的是,BCAP31与组织学分级和 p53 状态密切相关,这在 7 个 NSCLC 转录微阵列数据集队列中得到了验证。然后,转染了三种 NSCLC 细胞系,观察 BCAP31 引起的细胞行为变化,我们发现 BCAP31 的波动显著影响了 NSCLC 细胞的迁移和侵袭。为了确定 BCAP31 利用的途径,首先进行了基因集富集分析,显示 Akt/m-TOR/p70S6K 途径是显著的途径,这通过免疫荧光、激酶磷酸化和细胞行为观察得到了验证。最后,无标记质谱的数据表明 BCAP31 在一个基本的生物学过程中起作用。这项研究首次证明了 BCAP31 作为一种与转移相关的新型预后因素,并为 NSCLC 提供了一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f17b/7055246/e61a272db5d5/41598_2020_60905_Fig1_HTML.jpg

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