No abstract

Breast cancer antiestrogen resistance 4 (BCAR4) is a novel long noncoding RNA. It was originally identified in a screen for genes responsible for the development of resistance to antiestrogens in breast cancer cells and plays a major role in various tumors. However, the clinical diagnostic role of BCAR4 in tumors is not completely understood. This current meta‐analysis aimed to comprehensively explore the potential role of BCAR4 as a prognostic biomarker in a number of cancers. Five public databases PubMed, EMBASE, Web of Science, Wiley Online Library, and Medline were used to search for articles. Nine studies comprising 1,293 patients were included in this meta‐analysis. The results of analysis showed that BCAR4 expression in human cancer was significantly associated with poor overall survival (hazard ratio [HR] = 1.98, confidence interval [CI]: [1.71–2.29]), p < 0.00001, and high BCAR4 expression was associated with clinical stage (OR and its 95% CI was 3.30 [1.99–5.46], p < 0.00001), distant metastasis (OR = 3.83, 95% CI: 2.15–6.82, p < 0.00001), and lymph node metastasis (OR and its 95% CI was 2.91 [1.62–5.25], p = 0.0004) in patients with cancer. Furthermore, the results revealed the prognostic significance of BCAR4 in gastrointestinal malignancy, breast cancer, and osteosarcoma (HR and its 95% CI were 2.05 [1.56–2.68], p < 0.00001; 1.78 [1.46–2.16], p < 0.00001; and 2.47 [1.41–4.34], p < 0.00001, respectively). This meta‐analysis indicated the potential value of BCAR4 as a biomarker for predicting a poor prognosis in patients with cancer.

Adrenomedullin has been shown to be overexpressed in many tumors, including gastric cancer tumors; however, its mechanism of action remains unclear. In this study, we examined the role of adrenomedullin in the pathogenesis of gastric cancer. Using clinical specimens and immunohistochemistry, we found that the expression levels of adrenomedullin and its receptors are inordinately elevated as compared to the adjacent non-tumor gastric tissues. We used siRNA gene silencing, in BGC-823 gastric cancer cell lines, to target adrenomedullin genes, and found that increased adrenomedullin expression results in the proliferation of tumor cells, tumor invasion, and metastasis. Furthermore, we found that under hypoxic conditions, gastric cancer BGC-823 cells exhibit higher expression levels of adrenomedullin and various other related proteins. Our results indicate the involvement of adrenomedullin in microvessel proliferation and partially in the release of hypoxia in solid tumors. Knockdown of adrenomedullin expression, at the protein level, reduced the levels of phosphoprotein kinase B and B-cell lymphoma 2 but increased the levels of cleaved-caspase3 and Bcl 2 associated x protein (Bax). Therefore, we hypothesized siRNA targeting of adrenomedullin genes inhibits various serine/threonine kinases via a signaling pathway that induces cell apoptosis. SiRNA targeting of adrenomedullin genes and green fluorescent control vectors were used to transfect BGC-823 cells, and western blot analyses were used to detect changes in the rates of autophagy in related proteins using confocal laser scanning microscopy. No significant changes were detected. Therefore, the knockdown of adrenomedullin and its receptors may represent a novel treatment strategy for gastric cancer.