Identification of potential diagnostic biomarkers in MMPs for pancreatic carcinoma

Xie, Jingwei; Zhou, Xianzhu; Wang, Rui; Zhao, Jiulong; Tang, Jian; Zhang, Qichen; Du, Yiqi; Pang, Yanan

doi:10.1097/md.0000000000026135

Cited by 9 publications

(8 citation statements)

References 70 publications

(197 reference statements)

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“…As a crucial member of the MMP family, the aberrant expression of matrix metalloproteinase-1 (MMP1) has involved in various behaviors of cancer. Elevated expression of MMP1 and its prognostic value have been revealed in colorectal cancer [ 11 ], cervical squamous cell carcinoma [ 12 ], uveal melanoma [ 13 ], and colon cancer [ 14 ]. In addition, MMP1 has been identified as an oncogene facilitating the proliferation and migration of cutaneous squamous cell carcinoma (CSCC) via the activation of Wnt pathway [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

Zhang

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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Matrix metalloproteinase-1 (MMP1) has been reported to play key roles in a variety of cancers by degrading the extracellular matrix. However, its carcinogenic roles have not been shown yet in head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate its expression pattern and functional roles as well as clinical significance in HNSCC. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and immunohistochemistry (IHC) were utilized to determine the MMP1 expression pattern and the associations between its expression and patients’ outcome in HNSCC. Mice tongue squamous cell carcinoma model induced by 4-nitroquinoline 1-oxide (4NQO) and siRNA-mediated cellular assay in vitro were utilized to evaluate the oncogenic role of MMP1. The biological functions and cancer-related pathways involved in MMP1-related genes were found through bioinformatics analysis. Both mRNA and protein abundance of MMP1 were highly increased in HNSCC as compared to its non-tumor counterparts. MMP1 overexpression positively correlated with advanced tumor size, cervical node metastasis, and advanced pathological grade and lower patients’ survival. In the 4NQO-induced animal model, MMP1 expression increased along with the progression of the disease. In HNSCC cells, siRNA-mediated knockdown of MMP1 significantly inhibited cell proliferation, migration, and invasion and activated apoptosis and epithelia-mesenchymal transition (EMT). GSEA, GO, and KEGG analyses showed that MMP1 expression was significantly related to cancer-related pathways and cancer-related functions. Together, our results demonstrated MMP1 serves as a novel prognostic biomarker and putative oncogene in HNSCC.

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Section: Introductionmentioning

confidence: 99%

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

Zhang

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…It has been shown to be closely relevant to proliferation, migration and invasion in various cancers 37 . MMP1 can also promote the development of pancreatic cancer 38 , even become a potential diagnostic marker for pancreatic cancer 39 . However, there is less research on the regulation of MMP1 in the cancer acidic microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Enhanced pentose phosphate pathway activity promotes pancreatic ductal adenocarcinoma progression via activating YAP/MMP1 axis under chronic acidosis

Chen¹,

Ning²,

Song³

et al. 2022

Int. J. Biol. Sci.

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Background: Acidic microenvironment is a common physiological phenomenon in tumors, and is closely related to cancer development, but the effects of acidosis on pancreatic adenocarcinoma (PDAC) remains to be elucidated. Methods : Metabonomic assay and transcriptomic microarray were used to detect the changes of metabolites and gene expression profile respectively in acidosis-adapted PDAC cells. Wound healing, transwell and in vivo assay were applied to evaluate cell migration and invasion capacity. CCK8 and colony formation assays were performed to determine cell proliferation. Results: The acidosis-adapted PDAC cells had stronger metastasis and proliferation ability compared with the control cells. Metabonomic analysis showed that acidosis-adapted PDAC cells had both increased glucose and decreased glycolysis, implying a shift to pentose phosphate pathway. The metabolic shift further led to the inactivation of AMPK by elevating ATP. Transcriptomic analysis revealed that the differentially expressed genes in acidosis-adapted cells were enriched in extracellular matrix modification and Hippo signaling. Besides, MMP1 was the most upregulated gene in acidosis-adapted cells, mediated by the YAP/TAZ pathway, but could be reduced by AMPK activator. Conclusion : The present study showed that metabolic reprogramming promotes proliferation and metastasis of acidosis-adapted PDAC cells by inhibiting AMPK/Hippo signaling, thus upregulating MMP1.

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“…MMP12 was also revealed to be a potential diagnostic biomarker for pancreatic carcinoma. Its up-regulation was associated with a poor prognosis 64 . These genes were verified to be closely correlated with different cancers, especially the diagnosis and prognosis of PAAD, a finding we also made in this work.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic adenocarcinoma associated immune-gene signature as a novo risk factor for clinical prognosis prediction in hepatocellular carcinoma

Dai

Mugaanyi

Cai

et al. 2022

Sci Rep

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Pancreatic adenocarcinoma (PAAD) has high mortality and a very poor prognosis. Both surgery and chemotherapy have a suboptimal therapeutic effect, and this caused a need to find new approaches such as immunotherapy. Therefore, it is essential to develop a new model to predict patient prognosis and facilitate early intervention. Our study screened out and validated the target molecules based on the TCGA-PAAD dataset. We established the risk signature using univariate and multivariate Cox regression analysis and used GSE62452 and GSE28735 to verify the accuracy and reliability of the model. Expanded application of PAAD-immune-related genes signature (-IRGS) on other datasets was conducted, and the corresponding nomograms were constructed. We also analyzed the correlation between immune-related cells/genes and potential treatments. Our research demonstrated that a high riskscore of PAAD-IRGS in patients with PAAD was correlated with poor overall survival, disease-specific survival and progression free interval. The same results were observed in patients with LIHC. The models constructed were confirmed to be accurate and reliable. We found various correlations between PAAD-IRGS and immune-related cells/genes, and the potential therapeutic agents. These findings indicate that PAAD-IRGS may be a promising indicator for prognosis and of the tumor-immune microenvironment status in PAAD.

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Identification of potential diagnostic biomarkers in MMPs for pancreatic carcinoma

Cited by 9 publications

References 70 publications

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma

Enhanced pentose phosphate pathway activity promotes pancreatic ductal adenocarcinoma progression via activating YAP/MMP1 axis under chronic acidosis

Pancreatic adenocarcinoma associated immune-gene signature as a novo risk factor for clinical prognosis prediction in hepatocellular carcinoma

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