A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential

Abstract

Implication By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms. Background MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. Methods The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination. Results MMP1, MMP9 , MMP10 , MMP11 , and MMP13 were almost universally upregulated across all cancers, with significant ( p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3 , MMP7 , MMP12 and MMP14 ) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2 , MMP7 , MMP23B , MMP27 and MMP28 ) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma. Conclusions Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5768-0) contains supplementary material, which is available to authorized users.

Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling

“…Considerable experimental and clinical evidence documents that MMPs are involved in several steps of cancer development beside cell invasion and metastasis thus representing ideal pharmacological targets in tumor therapy 17 . Overexpression of MMPs has been associated with unfavorable outcomes in several malignant tumors, including breast 35,36 . Recent literature reported that naturally-derived plant polyphenols can block migration and invasion of breast cancer cells through a series of molecular mechanisms, including the downregulation of MMPs 37 .…”

Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer

“…It has been shown that MMP3 and CCN2 (aka connective tissue growth factor (CTGF)) are often increased in tumor-stroma tissues or patients' serum, and are thus biomarkers correlated with poor prognosis in cancer [18][19][20][21][22]. It has been also shown that MMP3 and CCN2/CTGF promote tumor progression through processes including rapid metastasis and tumor-stroma interactions [23][24][25][26].…”

Extracellular Oncosomes Rich in Moonlighting Metalloproteinase (MMP3) Are Transmissive, Pro-Tumorigenic, and Induces Cellular Communication Network Factor 2 (CCN2/CTGF): CRISPR against Cancer

“…It has been shown that MMP3 and CCN2 (also known as CTGF named after connective tissue growth factor) are often increased in tumor-stroma tissues or patient serum and are thus biomarkers correlated with poor prognosis in cancer [16][17][18][19][20]. It has been also shown that MMP3 and CTGF promote tumor progression including rapid metastasis and tumor-stroma interactions [21][22][23][24].…”