mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

Markić, Dean; Ćelić, Tanja; Gršković, Antun; Španjol, Josip; Fučkar, Željko; Grahovac, Blaženka; Đorđević, Gordana; Bobinac, Dragica

doi:10.1159/000330797

Cited by 14 publications

(9 citation statements)

References 49 publications

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“…This might be explained by the focus on all RCC of the previous study, while our study had specific focus on clear cell subtypes. Markic et al [23] had shown that all BMPs (BMP2, BMP4, BMP6, BMP7) and their receptors (BMPRIA, BMPRIB, and BMPRII) mRNA have stronger expression levels in RCC, especially BMP2 is elevated strongly in kidney cancer. Lee et al reported that BMP6 activated interleukin-10-mediated M2 polarization of tumor-associated macrophages to promote RCC growing.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma

Xiao

Wang

et al. 2019

Cancer Gene Ther

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Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMPs in ccRCC. Therefore, we screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for ccRCC patients with complete clinical information and BMP family expression data. Multivariate analysis showed that high expression of BMP1 was associated with shorter overall survival (OS) (P = 0.001), and shorter disease-free survival (DFS) (P = 0.018). Gene set enrichment analysis (GSEA) showed BMP1 was associated with epithelial-mesenchymal transition (EMT), G2M checkpoint, angiogenesis, hypoxia pathway, and Kirsten rat sarcoma viral oncogene (KRAS) signaling. Knockdown BMP1 suppressed malignancy of ccRCC in vitro and in vivo. Our results indicated that high expressions of BMP1 were poor prognostic factors and gene therapy could be an effective treatment for ccRCC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma

Xiao

Wang

et al. 2019

Cancer Gene Ther

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“…Recently, Wang et al [ 18 ] demonstrated that BMP-2 inhibits RCC growth by causing cell cycle arrest in the G1 phase. On the other hand, Markić et al [ 19 ] showed that expression levels of BMP-2 were strongly elevated with increased TNM stage in clinical RCC. However, the biological effects of BMP-2 on RCC development and progression remain to be fully elucidated, because only limited information is available for BMP-2 in human RCC.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

et al. 2015

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We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21WAF1/CIP1 and p27KIP1 expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2′-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC.

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“…Then, a personalized, predictive nomogram with a risk score was developed, which served as a predictive indicator; the signature encompassed a total of 14 IRGs. Among these, SAA1, TNFSF14, FGF21, IFNG, BMP7, and IL11 are biomarkers for predicting RCC outcomes (67)(68)(69)(70)(71)(72). For example, as a member of the serum amyloid A family of apolipoproteins, SAA1 can increase the invasive capacity of tumor cells in RCC by inducing MMP-9 expression (73), which make it serve as a biomarker for the diagnosis and prognosis of advanced and metastatic renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer

et al. 2021

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BackgroundRenal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients. Here, we aim to construct an immune prognostic predictive model to assist clinician to predict RCC prognosis.MethodsHerein, an immune prognostic signature was developed, and its predictive ability was confirmed in the kidney renal clear cell carcinoma (KIRC) cohorts based on The Cancer Genome Atlas (TCGA) dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.ResultsThe immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.ConclusionsThe immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.

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mRNA Expression of Bone Morphogenetic Proteins and Their Receptors in Human Renal Cell Carcinoma

Cited by 14 publications

References 49 publications

Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma

Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma

Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer

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