Increased BCAR1 Predicts Poor Outcomes of Non-small Cell Lung Cancer in Multiple-Center Patients

Abstract

Objective We aimed to study the prognostic value of BCAR1 expression and its associations with clinical-demographical characteristics in multiple centers of non-small cell lung cancer (NSCLC) patients. Methods Gene expression microarray (mRNA) of 77 adenocarcinomas from Mayo Clinic, RNA-sequencing of 508 NSCLC from The Cancer Genome Atlas (TCGA), and immunohistochemistry(IHC) stain of BCAR1-protein expression in 150 cases from Daping Hospital were included in the study. The association of mRNA or protein expression with patient clinical characteristics and overall survival was assessed in each dataset. We also predicted microRNAs (miRNA) that target BCAR1- using bioinformatics prediction tools and evaluated miRNA expression patterns with BCAR1 expression in miRNA-sequencing data of 74 lung cancer cases from TCGA dataset. Results In the Mayo Clinic dataset, a higher BCAR1-mRNA level was significantly correlated with more advanced tumor-stage and lymphatic metastasis. Similar changes were observed in the TCGA RNA-seq dataset. Additionally, higher BCAR1-mRNA levels predicted poorer survival in adenocarcinoma and squamous carcinoma from the TCGA dataset. The protein levels in the adenocarcinoma cases with lymphatic metastasis were significantly higher than of those without metastasis. Tumor tissues demonstrated remarkably higher levels of protein compared with matched normal tissues although there was no significant difference in BCAR1-mRNA expression between tumor and matched normal tissues was detected. In miRNAs that were down-regulated in the tumors, Let-7f-2 and miR-22 differed the most (P<0.001 and P=0.007, respectively). Conclusion We confirmed that increased BCAR1 expression predicts poorer prognosis in NSCLC. We postulate mRNA-protein decoupling of BCAR1 may be a result of reduced inhibition of specific miRNAs in tumor tissues, which warrants further study.

Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMN1

“…Deng et al found that miR-1247 was downregulated in lung squamous cell carcinoma tissue samples compared with normal tissues by a chip detection assay 14. Moreover, a functional role of miR-1247 has been found in a number of cancers, including prostate cancer,12 osteoblasts from osteosarcoma,11 and pancreatic cancer 28.…”

“…Moreover, the expression of miR-1247 has been found to be decreased in osteosarcoma cancer stem cells and influences human osteosarcoma oncogenesis by the regulation of MAP3K9 11. Furthermore, miR-1247 was found to be downregulated in lung adenocarcinoma and squamous carcinoma cancer tissue compared with normal tissues 14. Yet the function and mechanism of miR-1247 in NSCLC has rarely been explored.…”

Novel prognostic molecular markers in lung cancer (Review)

“…Patients with low RRM1 expression tend to have OS only less than 4 months longer in comparison to patients with high expression of the molecule (74). High expression of BCAR1 is a slightly more powerful prognostic factor of OS in NSCLC, as the HR in this case is ~2.5 (75). This data indicates that the novel markers are more powerful in predicting the course of LC.…”

Novel Germline Mutation in BCAR1 in Two Siblings With Lung Cancer: a Possible Susceptibility Gene

“…p130Cas is also reported to be involved in the development and progression of several human cancers, including breast cancer [19,20], prostate cancer [21,22], as well as lung cancer [23]. In lung cancer, BCAR1 was usually overexpressed, and increased BCAR1 predicts poorer prognosis in non-small lung cancer [23,24]. In this report, the detected BCAR1 variant occurred an 11 bp insertion at codon 314 which locates at the substrate binding domain, indicating that its association with effectors proteins would be impaired in some extent, thus leading to a wide-range downstream consequence.…”