Serum bradykinin levels as a diagnostic marker in cervical cancer with a potential mechanism to promote VEGF expression via BDKRB2

Abstract

Bradykinin (BK) is one of the kinin peptides and preferentially binds to bradykinin B2 receptor (BDKRB2). A recent study indicated that BK played an important role in the occurrence and progression of cancer. In this study, we evaluated the serum BK levels in 130 cervical cancer (CC) cases (including 65 cases with pre- and post-surgery paired samples, another 65 cases with only pre-surgery samples), 35 cervical intraepithelial neoplasia (CIN) cases (pre- and post-surgery paired) and 35 control cases. We found that BK was overexpressed in patients with CC compared to patients with CIN and the control group. When combined with squamous cell carcinoma-related antigen (SCCA), the diagnostic efficacy of BK was prominently enhanced. Moreover, we detected the expression level of the BK receptor BDKRB2 in CC, CIN and normal cervical tissues and observed a higher expression in the CC and CIN tissues than in the normal cervix. We then explored the possible mechanisms of action of BK in promoting the progression of CC. When BK was added to the cell culture medium, human umbilical vein endothelial cell (HUVEC) angiogenesis increased and vascular endothelial growth factor (VEGF) expression in CC cell lines was also elevated. The BK antagonist, HOE140, exerted an opposite effect. The knockdown or the overexpression of BDKRB2 in CC cell lines further confirmed its oncogenic role in angiogenesis. Taken together, the findings of this study suggest that BK may be a diagnostic biomarker for CC and may notably improve the diagnostic efficacy when combined with SCCA. BK promotes the progression of CC by upregulating the expression of VEGF via BDKRB2 and subsequently facilitating angiogenesis.

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

“…Notably, according to their nearby genes, the present study was also able to identify a few tumor-associated lncRNAs altered in BC. ENST00000562848, ENST00000587187, ENST00000398878, ENST00000421206, ENST00000443576 and ENST00000562393 are spliced from the neighboring areas of HOXC6 ( 58 ), UHRF1 ( 59 ), SULT1A3 ( 60 ), GRK5 ( 61 ), STARD13 ( 62 ) and BDKRB2 ( 63 ), which plays a critical role in malignant proliferation, migration and metastasis. Overall, these findings indicated that these lncRNAs are associated with a diverse range of different types of cancer, thereby emphasizing the accuracy of the sequencing data in the present study, and indicating the potential critical role of these lncRNAs in the development of BC as well.…”

A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors

“…Of the two, B1R expression is considered the more ideal target because of its low expression in normal tissues. B1R activation has been shown to potentiate malignant behaviors by inducing cell proliferation, migration, and angiogenesis [ 59 , 60 , 61 ]. The pro-inflammatory effect of B1R activation can modulate the tumor microenvironment, priming for distant metastasis [ 62 ].…”

Serum Actinin-4 Levels as a Potential Diagnostic and Prognostic Marker in Cervical Cancer

“…In recent years, the incidence of CC has increased greatly in young women under the age of 35 [2]. Despite great advances in surgical and adjuvant therapy, the overall survival of CC patients, especially that of advanced patients, is still very poor [3]. At present, a Pap smear combined with an HPV test has been used for the early screening of cervical lesions.…”

“…At present, a Pap smear combined with an HPV test has been used for the early screening of cervical lesions. However, the screening methods are invasive and costly, leading to lower screening coverage in China [3]. Previous studies have reported that the human papillomavirus (HPV) screening results have a relatively high false-positive rate and a relatively low specificity [4,5].…”