High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

Niu, Haitao; Li, Feng; Wang, Qingshui; Ye, Zhoujie; Chen, Qi; Lin, Yao

doi:10.7717/peerj.5050

Cited by 29 publications

(21 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the present findings, Niu et al . found that RAP1B mRNA levels are elevated in ccRCC tissues relative to adjacent normal renal tissues . Additionally, Wang et al .…”

Section: Discussionmentioning

confidence: 95%

“…38,39 Consistent with the present findings, Niu et al found that RAP1B mRNA levels are elevated in ccRCC tissues relative to adjacent normal renal tissues. 40 Additionally, Wang et al showed that the RAP1B expression was significantly elevated in RCC tumors compared to nontumorous tissues. 41 In addition, we found that C12orf49 and EHD4 could significantly distinguish early-stage ccRCC from renal oncocytoma (≤4 cm).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Searching for prognostic biomarkers for small renal masses in the urinary proteome

Meo

Batruch

Brown

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early‐stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label‐free liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) proteomics approach and targeted parallel‐reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC‐SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)‐SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC‐SRMs (ccRCC‐SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC‐SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC‐SRMs. A two‐protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70–0.93) in distinguishing progressive from nonprogressive ccRCC‐SRMs. Patients (Stage I–IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10−6) compared to patients with no alterations. Our in‐depth proteomic analysis identified novel biomarkers for early‐stage RCC‐SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.

show abstract

“…Consistent with the present findings, Niu et al . found that RAP1B mRNA levels are elevated in ccRCC tissues relative to adjacent normal renal tissues . Additionally, Wang et al .…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Searching for prognostic biomarkers for small renal masses in the urinary proteome

Meo

Batruch

Brown

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Ma et al reported that the level of MMP9 is higher in metastatic ccRCC than in primary ccRCC (47). The level of MMP9 is associated with poor prognosis in ccRCC patients (48). These results indicate that the hub genes may play a key role in the network of immune-related genes.…”

Section: Discussionmentioning

confidence: 96%

Identification of Immune-Related Cells and Genes in Tumor Microenvironment of Clear Cell Renal Cell Carcinoma

Zhou

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immunerelated genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

show abstract

“…For the invasion and dissemination of tumor cells MMPs‐mediated extracellular matrix degradation is required . MMP9 is among the major players of MMP family and has been linked to invasiveness and aggressiveness of cancer cells . The modulation of MMP9 expression by ZEB2 was previously reported in gastric cancers .…”

Section: Discussionmentioning

confidence: 96%

ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors

Yalim-Camci

Balçık-Erçin

Çetįn

et al. 2019

Molecular Carcinogenesis

View full text Add to dashboard Cite

Epithelial‐mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E‐box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Recently, expression of MMPs was associated to the activation of ETS1 transcription factor; however, a link between ZEB2 and ETS proto‐oncogene 1, transcription factor (ETS1) remains to be elucidated. Hence, we investigated the transcriptional regulation of ETS1 by ZEB2 after our initial observation that ZEB2 and ETS1 are coexpressed in hepatocellular carcinoma cells (HCCs). Chromatin immunoprecipitation and luciferase reporter assays clearly showed that ZEB2 binds to E‐box sequences on the promoter of ETS1. Elevated expression of ETS1 was found in DLD‐ZEB2 and A431‐ZEB2 inducible systems, and knockdown of ZEB2 caused an explicit downregulation of ETS1 in shZEB2‐SNU398 and shZEB2‐SK‐HEP‐1 cells. Repression of ETS1 expression in ZEB2‐induced conditions substantially impaired the migration and invasive capacities of DLD1 cells. Mechanistically, knockdown of ETS1 in ZEB2‐expressing cells resulted in the downregulation of established ZEB2 targets TWIST and MMP9. Correlation analyses in HCC lines, cancer complementary DNA arrays, and The Cancer Genome Atlas RNA‐sequencing data set revealed that ZEB2 and ETS1 are coexpressed, and their expressions in human tumors show a highly significant positive correlation. Our results demonstrated that ZEB2 acts as an upstream regulator of ETS1 and, in turn, ETS1 maintains ZEB2‐induced EMT. These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.

show abstract

High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

Cited by 29 publications

References 21 publications

Searching for prognostic biomarkers for small renal masses in the urinary proteome

Searching for prognostic biomarkers for small renal masses in the urinary proteome

Identification of Immune-Related Cells and Genes in Tumor Microenvironment of Clear Cell Renal Cell Carcinoma

ETS1 is coexpressed with ZEB2 and mediates ZEB2‐induced epithelial‐mesenchymal transition in human tumors

Contact Info

Product

Resources

About