Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer

Liang, Yu‐Xiang; Mo, Rujun; He, Hui‐Chan; Chen, Jiahong; Zou, Jun; Han, Zhengxue; Lü, Jianming; Cai, Chao; Zeng, Yanru; Zhong, Weide; Wu, Chin‐Lee

doi:10.3892/or.2015.3870

Cited by 8 publications

(3 citation statements)

References 26 publications

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“…Kong et al recently showed that hypomethylation in a specific CD147/ BSG promoter region, comprising SP1 binding sites, leads to upregulation of CD147 expression and is associated with poor prognosis in HCC [ 15 ]. Liang et al also showed that CD147 hypomethylation is associated with overexpression and tumor progression in prostate cancer [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma

Fisel

Stühler²,

Bedke

et al. 2015

Oncotarget

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Cluster of differentiation 147 (CD147/BSG) is a transmembrane glycoprotein mediating oncogenic processes partly through its role as binding partner for monocarboxylate transporter MCT4/SLC16A3. As demonstrated for MCT4, CD147 is proposed to be associated with progression in clear cell renal cell carcinoma (ccRCC). In this study, we evaluated the prognostic relevance of CD147 in comparison to MCT4/SLC16A3 expression and DNA methylation.MethodsCD147 protein expression was assessed in two independent ccRCC-cohorts (n = 186, n = 59) by immunohistochemical staining of tissue microarrays and subsequent manual as well as automated software-supported scoring (Tissue Studio, Definien sAG). Epigenetic regulation of CD147 was investigated using RNAseq and DNA methylation data of The Cancer Genome Atlas. These results were validated in our cohort. Relevance of prognostic models for cancer-specific survival, comprising CD147 and MCT4 expression or SLC16A3 DNA methylation, was compared using chi-square statistics.ResultsCD147 protein expression generated with Tissue Studio correlated significantly with those from manual scoring (P < 0.0001, rS = 0.85), indicating feasibility of software-based evaluation exemplarily for the membrane protein CD147 in ccRCC. Association of CD147 expression with patient outcome differed between cohorts. DNA methylation in the CD147/BSG promoter was not associated with expression. Comparison of prognostic relevance of CD147/BSG and MCT4/SLC16A3, showed higher significance for MCT4 expression and superior prognostic power for DNA methylation at specific CpG-sites in the SLC16A3 promoter (e.g. CD147 protein: P = 0.7780, Harrell's c-index = 53.7% vs. DNA methylation: P = 0.0076, Harrell's c-index = 80.0%).ConclusionsPrognostic significance of CD147 protein expression could not surpass that of MCT4, especially of SLC16A3 DNA methylation, corroborating the role of MCT4 as prognostic biomarker for ccRCC.

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Section: Discussionmentioning

confidence: 99%

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma

Fisel

Stühler²,

Bedke

et al. 2015

Oncotarget

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“…CD147 has a broad tissue distribution, but its overexpression is also seen in breast cancers, HCC, esophageal and cervical squamous cell carcinoma, genitourinary, gastric, colorectal, prostate and ovarian cancers [ 1 , 2 , 17 ]. Liang et al [ 18 ] found that promoter hypomethylation of CD147 might result in the cancer-related overexpression of CD147 because more Sp1 protein bound to its promoter [ 18 , 19 ]. Wang et al [ 20 ] showed that CD147 silencing inhibited cell proliferation, invasion and increased chemosensitivity to cisplatin in SGC7901 cells in vitro .…”

Section: Introductionmentioning

confidence: 99%

CD147 expression was positively linked to aggressiveness and worse prognosis of gastric cancer: a meta and bioinformatics analysis

Zheng

Gong

2017

Oncotarget

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CD147 (also named as Basigin or EMMPRIN) might promote cancer invasion and metastasis by inducing MMP and VEGF synthesis in tumor microenvironment. We performed a systematic meta and bioinformatics analysis through multiple online databases up to March 14, 2017. Up-regulated CD147 expression was found in gastric cancer, compared with normal mucosa (p < 0.05). The male patients with gastric cancer showed higher CD147 expression than the female ones (p < 0.0001). CD147 expression was positively correlated with tumor size, depth of invasion, lymph node metastasis, TNM staging and unfavorable prognosis of gastric cancer (p < 0.05). At mRNA level, CD147 expression was higher in intestinal-type and mixed-type gastric carcinomas than normal tissues (p < 0.05). CD147 mRNA expression was negatively associated with histological grading and dedifferentiation of gastric cancer (p < 0.05). A higher CD147 mRNA expression was negatively correlated with overall and progression-free survival rates of all cancer patients, even stratified by clinicopathological features (p < 0.05). These findings indicated that CD147 expression might be employed as a potential marker to indicate gastric carcinogenesis and subsequent progression, even prognosis.

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“…Promotes aggressive tumor progression in human PC (119) TFF1 and TFF3 Their overexpression in PC may serve as biomarkers (120) resistance in GC cells, ubenimex epigenetically inhibits the activation of the CD13/EMP3/PI3K/AKT/NF-κB pathway (154). Additionally, the NFκB pathway participates in the acquisition of resistance to tyrosine kinase inhibitor (TKI) treatment in lung cancer.…”

Section: Cd147mentioning

confidence: 99%

Role of DNA Methylation in the Resistance to Therapy in Solid Tumors

Romero-García¹,

Prado-Garcı́a²,

Carlos‐Reyes³

2020

Front. Oncol.

106

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Despite the recent advances in chemotherapeutic treatments against cancer, some types of highly aggressive and invasive cancer develop drug resistance against conventional therapies, which continues to be a major problem in the fight against cancer. In recent years, studies of alterations of DNA methylome have given us a better understanding of the role of DNA methylation in the development of tumors. DNA methylation (DNAm) is an epigenetic change that promotes the covalent transfer of methyl groups to DNA. This process suppresses gene expression through the modulation of the transcription machinery access to the chromatin or through the recruitment of methyl binding proteins. DNAm is regulated mainly by DNA methyltransferases. Aberrant DNAm contributes to tumor progression, metastasis, and resistance to current anti-tumoral therapies. Aberrant DNAm may occur through hypermethylation in the promoter regions of tumor suppressor genes, which leads to their silencing, while hypomethylation in the promoter regions of oncogenes can activate them. In this review, we discuss the impact of dysregulated methylation in certain genes, which impact signaling pathways associated with apoptosis avoidance, metastasis, and resistance to therapy. The analysis of methylome has revealed patterns of global methylation, which regulate important signaling pathways involved in therapy resistance in different cancer types, such as breast, colon, and lung cancer, among other solid tumors. This analysis has provided gene-expression signatures of methylated region-specific DNA that can be used to predict the treatment outcome in response to anti-cancer therapy. Additionally, changes in cancer methylome have been associated with the acquisition of drug resistance. We also review treatments with demethylating agents that, in combination with standard therapies, seem to be encouraging, as tumors that are in early stages can be successfully treated. On the other hand, tumors that are in advanced stages can be treated with these combination schemes, which could sensitize tumor cells that are resistant to the therapy. We propose that rational strategies, which combine specific demethylating agents with conventional treatment, may improve overall survival in cancer patients.

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Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer

Cited by 8 publications

References 26 publications

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma

CD147 expression was positively linked to aggressiveness and worse prognosis of gastric cancer: a meta and bioinformatics analysis

Role of DNA Methylation in the Resistance to Therapy in Solid Tumors

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