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

Emily Gobin,Robert Schleifer,Ashok Sharma,Kayla Bagwell,David Mysona,Sharmila Sandirasegarane,Nathan Smith,Jin-Xiong She,Shan Bai,John Wagner

doi:10.1186/s12885-019-5768-0

Abstract

ImplicationBy understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms.BackgroundMMPs 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.MethodsThe 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.ResultsMMP1, 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.ConclusionsMost 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.

Highlights

Matrix Metalloproteases (MMP) are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance
Survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma
MMP expression difference between Cancer and Normal Gene expression differences for the twenty-four MMP family members were analyzed in fifteen different cancer types in the Cancer Genome Atlas (TCGA) (Fig. 1)

Summary

Introduction

MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. MMPs have been extensively studied for nearly 40 years and originally were noted for their role in degrading the extracellular matrix (ECM) [1]. The catalytic domains add specificity to the target for degradation of each MMP. MMPs have been found to play a remarkable number of regulatory roles at the cellular level in pathways such as apoptosis, immunity, cellular migration, and angiogenesis [2]. MMP functionality often complements classical tumor properties leading to invasion, immune system avoidance, and metastasis. Given these qualities, MMPs play a major role in carcinogenesis [1,2,3,4].

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