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.
Highlights
Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage
To investigate the clinical significance of B cell receptor-associated protein 31 (BCAP31) in NSCLC, we examined the expression of three well-known tumor markers, calreticulin (CRT), glucose-regulated protein 78 (GRP78) and glucose-regulated protein 94 (GRP94), as parallel control
We firstly revealed the clinical importance of BCAP31 in NSCLC, and that it was closely associated with cancer development
Summary
Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage. 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 BCAP31, predicted inferior overall survival. Described in patients with malignant melanoma[4], CTAs have been identified as biomarkers for a diverse range of cancers, including NSCLC5. Their expression is often coordinated[6], and associated with poor clinical outcome[7] and advanced stage[8], metastasis[9]. (BAP31/BCAP31) is a CTA-like protein which is highly expressed in many forms of cancer, including lung cancer
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